Clinical Trials

Filter by condition

61 studies in Division of Hematology Research

  1. A Phase 1 Study of CPI-0610, a Small Molecule Inhibitor of BET (Bromodomain and Extra-terminal) Proteins, in Patients With Previously Treated Multiple Myeloma

    Phoenix/Scottsdale, Ariz. View Summary

    A Phase 1 Study of CPI-0610, a Small Molecule Inhibitor of BET (Bromodomain and Extra-terminal) Proteins, in Patients With Previously Treated Multiple Myeloma

    Location:

    Phoenix/Scottsdale, Ariz.

    Trial status:

    Open for Enrollment

    Why is this study being done?

    Open-label, sequential dose escalation and expansion study of CPI-0610 in patients with previously treated multiple myeloma. CPI-0610 is a small molecule inhibitor of bromodomain and extra-terminal (BET) proteins.

    NCT ID:

    NCT02157636

    IRB Number:

    13-008753

    Who can I contact for additional information about this study?


    Scottsdale: Clinical Trials Office All Mayo Clinic Locations 507-538-7623
                        

  2. A 3-Arm Randomized Phase II Trial of Bendamustine-Rituximab (BR) Followed by Rituximab vs Bortezomib-BR (BVR) Followed by Rituximab vs BR Followed by Lenalidomide/Rituximab in High Risk Follicular Lymphoma

    Rochester, Minn. View Summary

    A 3-Arm Randomized Phase II Trial of Bendamustine-Rituximab (BR) Followed by Rituximab vs Bortezomib-BR (BVR) Followed by Rituximab vs BR Followed by Lenalidomide/Rituximab in High Risk Follicular Lymphoma

    Location:

    Rochester, Minn.

    Trial status:

    Open for Enrollment

    Why is this study being done?

    OBJECTIVES: Primary - To compare the complete remission rate in patients with high-risk follicular lymphoma receiving induction therapy comprising bendamustine hydrochloride and rituximab with vs without bortezomib. - To compare the 1-year post-induction disease-free survival rate in patients receiving continuation therapy comprising rituximab with vs without lenalidomide. Secondary - To determine the 3-year progression-free survival and the 5-year overall survival of these patients. - To evaluate patient-reported outcomes at baseline and during treatment to determine differences in symptom palliation, treatment-related symptoms, and overall health-related quality of life. - To examine the association between baseline FLIPI information and outcome of these patients. - To examine the association between baseline and end-of-treatment patient comorbidities assessed by the Cumulative Illness Rating Scale (CIRS) and outcome. - To create an image and tissue bank including serial PET/CT scans, diagnostic paraffin-embedded tissue, germline DNA, and serial blood and bone marrow samples sufficient to support proposed and future studies of tumor and host characteristics that may predict for clinical outcome, including treatment arm effects, and enhance existing prognostic indices. (exploratory) OUTLINE: Patients are stratified according to FLIPI-1score (1 or 2 vs 3 vs 4 or 5) and GELF tumor burden (low vs high). Patients are randomized to 1 of 3 treatment arms. - Arm I: Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. - Arm II: Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, patients receive rituximab as in arm I. - Arm III: Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Immediately after completing induction therapy, patients receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Quality of life (including fatigue, neurotoxicity, anxiety, and depression) is assessed by questionnaire at baseline and periodically during study therapy. Blood, bone marrow, and tissue samples may be collected periodically for correlative studies and for a repository. After completion of study therapy, patients are followed up periodically for 15 years.

    NCT ID:

    NCT01216683

    IRB Number:

    10-007760

    Who can I contact for additional information about this study?

    Rochester: Clinical Trials Office - All Mayo Clinic Locations 507-538-7623
                        


  3. LS1081, "A Pilot Study of Dendritic Cell Therapy Delivered Intratumorally After Cryoablation or Intradermally for Patients With B-Cell Non-Hodgkin s Lymphoma"

    Rochester, Minn. View Summary

    LS1081, "A Pilot Study of Dendritic Cell Therapy Delivered Intratumorally After Cryoablation or Intradermally for Patients With B-Cell Non-Hodgkin s Lymphoma"

    Location:

    Rochester, Minn.

    Trial status:

    Open for Enrollment

    Why is this study being done?

    PRIMARY OBJECTIVES: I. Evaluation of safety and tolerability as measured by the incidence of significant toxicity of an autologous DC vaccine injection into a cryoablated tumor site (Arm A). II. Evaluation of safety and tolerability as measured by the incidence of significant toxicity of an autologous mature DC vaccine + tumor lysate generated in vitro and delivered intradermally (ID) (Arm B). SECONDARY OBJECTIVES: I. For cryoablation candidates: To assess feasibility, overall response rate, clinical benefit rate, time to response, and duration of response (Arm A). II. For patients receiving ID vaccine without cryoablation: To assess feasibility, clinical response rate, time to response, and duration of response (Arm B). TERTIARY OBJECTIVES: I. For cryoablation candidates: To assess the change over time in non-cryoablated nodes selected as the index lesions (Arm A). II. For patients receiving ID vaccine without cryoablation: To assess the change over time in measurable nodes selected as the index lesions (Arm B). III. To monitor patients' immune response after vaccine therapy. IV. Assess the immune response to Prevnar in cancer patients. V. Assess the effect of DC vaccination on presence of myeloid suppressors. VI. Assess the effect of tumor antigen delivery methods (in vivo DC into cryoablated tumor vs. ID injection of in vitro generated DC + lysate) on T cell response. OUTLINE: Patients are assigned to 1 of 2 treatment arms. In both arms, treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year, and then every 6 months for up to 2.5 years.

    NCT ID:

    NCT01239875

    IRB Number:

    10-003023

    Who can I contact for additional information about this study?

    Rochester: Mayo Clinic Clinical Trials Office 507-538-7623
                        


  4. Classification of Newly Diagnosed Acute Lymphoblastic Leukemia (ALL)

    Rochester, Minn. View Summary

    Classification of Newly Diagnosed Acute Lymphoblastic Leukemia (ALL)

    Location:

    Rochester, Minn.

    Trial status:

    Open for Enrollment

    Why is this study being done?

    PRIMARY OBJECTIVES: I. To provide a risk-based classification system based on clinical, pathological, molecular, and early response data that will be used to assign all patients with newly diagnosed acute lymphoblastic leukemia (ALL) to the Children's Oncology Group (COG) frontline specific-treatment studies. II. To capture classification data for correlative studies accompanying current COG ALL treatment protocols. III. To provide a central reference guide for all required and research studies that will be conducted in local and reference laboratories for all newly diagnosed ALL patients. IV. To provide a mechanism for optional banking of leukemia and germline specimens for current and future research. OUTLINE: This is a multicenter study. Patients are stratified according to diagnosis (B-cell precursor vs infant vs T-cell acute lymphoblastic leukemia [ALL]). Patients undergo blood sample collection and bone marrow biopsies at baseline and during and after induction therapy for immunophenotyping for ALL confirmation and classification, deoxyribonucleic acid (DNA) ploidy, genomic variation, and cytogenetic (BCR-ABL, trisomies 4+10, and molecular testing for translocations) analysis by flow cytometry and fluorescent in situ hybridization (FISH). Immunophenotype results obtained on this study are used to determine patient's assignment to specific clinical-trial treatments. Some samples (leukemic and germline) may be banked for current and/or future analyses.

    NCT ID:

    NCT01142427

    IRB Number:

    10-005587

    Who can I contact for additional information about this study?

    Rochester: Vilmarie Rodriguez 507-538-7623
                        


  5. A Phase 1/2, Open-label, Dose-Escalation Multi-center Study to Assess the Safety, Tolerability, PK and PD of Orally Administered NS-018 in Patients With Primary Myelofibrosis (MF), Post-polycythemia Vera MF, or Post-essential Thrombocythemia MF

    Phoenix/Scottsdale, Ariz. View Summary

    A Phase 1/2, Open-label, Dose-Escalation Multi-center Study to Assess the Safety, Tolerability, PK and PD of Orally Administered NS-018 in Patients With Primary Myelofibrosis (MF), Post-polycythemia Vera MF, or Post-essential Thrombocythemia MF

    Location:

    Phoenix/Scottsdale, Ariz.

    Trial status:

    Open for Enrollment

    Why is this study being done?

    The purpose of this study is to determine the safety and tolerability of orally administered NS-018 in patients with Primary Myelofibrosis (PMF), Post-polycythemia Vera Myelofibrosis (post-PV MF), or Post-essential Thrombocythemia Myelofibrosis (post-ET MF)

    NCT ID:

    NCT01423851

    IRB Number:

    11-000895

    Who can I contact for additional information about this study?


    Scottsdale: Clinical Trials Office - All Mayo Clinic Locations 507-538-7623
                        

  6. A Randomized Controlled Phase 3 Study of Oral Pacritinib Versus Best Available Therapy in Patients With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis

    Phoenix/Scottsdale, Ariz. View Summary

    A Randomized Controlled Phase 3 Study of Oral Pacritinib Versus Best Available Therapy in Patients With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis

    Location:

    Phoenix/Scottsdale, Ariz.

    Trial status:

    Open for Enrollment

    Why is this study being done?

    The primary hypothesis of the study is that treatment with pacritinib results in a greater proportion of patients achieving ≥ 35% reduction in spleen volume from baseline to Week 24 than treatment with BAT.

    NCT ID:

    NCT01773187

    IRB Number:

    13-000658

    Who can I contact for additional information about this study?

  7. Phase IIIB, Open-label, Multi-Center Study of the Efficacy and Safety of Rigosertib Administered as 72-hour Continuous Intravenous Infusions in Patients With Myelodysplastic Syndrome With Excess Blasts Progressing On or After Azacitidine or Decitabine

    Rochester, Minn. View Summary

    Phase IIIB, Open-label, Multi-Center Study of the Efficacy and Safety of Rigosertib Administered as 72-hour Continuous Intravenous Infusions in Patients With Myelodysplastic Syndrome With Excess Blasts Progressing On or After Azacitidine or Decitabine

    Location:

    Rochester, Minn.

    Trial status:

    Open for Enrollment

    Why is this study being done?

    This study will examine the effect intravenously administered rigosertib has on the relationship between bone marrow blasts response and overall survival in myelodysplastic syndromes (MDS) patients who have 5-30% bone marrow blasts and who progressed on or after treatment with azacitidine or decitabine.

    NCT ID:

    NCT01928537

    IRB Number:

    13-003625 13-009041

    Who can I contact for additional information about this study?

  8. Intergroup Trial for Children or Adolescents With B-Cell NHL or B-AL: Evaluation of Rituximab Efficacy and Safety in High Risk Patients

    Rochester, Minn. View Summary

    Intergroup Trial for Children or Adolescents With B-Cell NHL or B-AL: Evaluation of Rituximab Efficacy and Safety in High Risk Patients

    Location:

    Rochester, Minn.

    Trial status:

    Open for Enrollment

    Why is this study being done?

    PRIMARY OBJECTIVES: I. For the patients with advanced stage B-cell non-Hodgkin lymphoma (NHL)/Burkitt leukemia (B-AL) (stage III and lactate dehydrogenase (LDH) > Nx2, any stage IV or B-AL), to test whether adding 6 injections of rituximab to standard LMB chemotherapy regimen, improves the event-free survival (EFS) compared with LMB chemotherapy alone. (Phase III) II. For patients with primary mediastinal large B-cell lymphoma (PMLBL), to evaluate the EFS following treatment with the regimen dose-adjusted (DA)-etoposide, prednisone, vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride (EPOCH), and rituximab. (Phase II) SECONDARY OBJECTIVES: I. To study the complete remission (CR) rate and the overall survival (OS). II. To evaluate safety on all study arms including toxic deaths, adverse events recorded using the National Cancer Institute (NCI)-Common Terminology Criteria (CTC) V4 (non-hematological toxicity grade 3, infections grade 3 to 5), cardiac toxicity (CTC grade 2-5 and evolution of left ventricular ejection fraction [LVEF] and left ventricular shortening fraction [LVSF]), number of days with platelets transfusion, intensive-care unit admission, number of days with red cells transfusion, and rituximab infusion reactions. III. To study the rate of patients with immunoglobulin (Ig; G, A, and M) levels abnormally low and lymphocyte count abnormally low at 1 year and until 5-year follow-up, to study the need for Ig infusions, and levels of post (previous and re-) vaccination antibodies at 1 year. IV. To study long-term (at least 5 years) risks of the use of rituximab plus chemotherapy compared with LMB chemotherapy alone in children with advanced stage B-NHL/B-AL (all events related [certain and probable] to therapy). (Phase III) V. To study the long-term risk of DA-EPOCH-R regimen, especially the cardiac risk related to doxorubicin given at higher dose than usual in children, but infused over 96 hours (i.e., evaluation of CTC grade 2-5 and evolution of LVEF and LVSF). (Phase II) TERTIARY OBJECTIVES: I. To obtain data on positron emission tomography (PET)-computed tomography (CT) scan in childhood pediatric B-cell NHL. (Exploratory) II. To evaluate the potential prognostic value of Minimal Disseminated Disease (MDD) and Minimal Residual disease (MRD) in correlation with outcome. (Exploratory - Phase III) III. To perform an economic study comparing the cost-effectiveness ratio between 2 therapeutic strategies: LMB chemotherapy with versus without rituximab. (Exploratory - Phase III) IV. To characterize the pharmacokinetics of rituximab in combination with LMB chemotherapy in a subset of patients. (Exploratory - Phase III) OUTLINE: This is a multicenter study. Phase II (patients with PMLBL): Patients receive rituximab IV on day 1; prednisone orally (PO) twice daily (BID) or IV on day on days 1-5; etoposide IV continuously on days 1-4; doxorubicin hydrochloride IV continuously on days 1-4; vincristine sulfate IV continuously on days 1-4; and cyclophosphamide IV on day 5. Patients also receive filgrastim subcutaneously (SC) once daily (QD) beginning on day 6 until blood count recovers. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Phase III: Patients are stratified according to National Group (COG vs SFCE vs UK NCRI CCL CSG vs AIEOP vs BSPHO vs DCOG vs SEHOP vs PPLLSG vs Hungarian Society of Pediatric Oncologist and Pediatric Hematologist), histology (large cell vs non large cell [Burkitt, atypical Burkitt, B-AL, or L3-AL]), and chemotherapy group (1 vs 2). Patients are assigned to 1 of 2 treatment groups. Group 1 (pre-phase central nervous system [CNS]-negative, cerebral spinal fluid [CSF]-negative): Patients receive vincristine sulfate IV on day 1; cyclophosphamide IV over 15 minutes on day 1; prednisone PO BID or methylprednisolone IV on days 1-7; methotrexate intrathecally (IT) and hydrocortisone IT on day 1. Patients are randomized to 1 of 2 treatment arms. Arm I (R-COPADM induction therapy): Beginning 8 days later, patients receive rituximab IV on day 1; vincristine sulfate IV on day 1; prednisone PO BID or methylprednisolone IV on days 1-5; methotrexate IV over 3 hours on day 1; leucovorin calcium PO every 6 hours on days 2-4; cyclophosphamide IV over 15 minutes on days 2-4; doxorubicin hydrochloride over 1 hour on day 2; and methotrexate IT and hydrocortisone IT on days 2 and 6. Treatment repeats every 18-21 days for 2 courses. Consolidation therapy (R-COPADM): Patients receive rituximab IV on day 1; methotrexate IV over 3 hours on day 1; leucovorin calcium PO every 6 hours on days 2-4; cytarabine IV continuously on days 2-6; methotrexate IT on day 2; hydrocortisone IT on days 2 and 7; and cytarabine IT on day 7. Treatment repeats every 21 days for 2 courses. Arm II (COPADM induction therapy): Beginning 8 days later, patients receive vincristine sulfate, prednisone or methylprednisolone, methotrexate, leucovorin calcium, cyclophosphamide, doxorubicin, methotrexate IT, and hydrocortisone IT as in arm I. Treatment repeats every 18-21 days for 2 courses. Consolidation therapy (COPADM): Patients receive methotrexate IV over 3 hours on day 1; leucovorin calcium PO every 6 hours on days 2-4; cytarabine IV over 12 hours on days 2-6; methotrexate IT on day 2; hydrocortisone IT on days 2 and 7; and cytarabine IT on day 7. Treatment repeats every 21 days for 2 courses. Group 2 (pre-phase B-AL, CNS-negative OR CNS-positive, CSF-negative OR CSF-positive): Patients receive vincristine sulfate IV on day 1; cyclophosphamide IV over 15 minutes on day 1; prednisone PO BID or methylprednisolone IV on days 1-7; methotrexate IT, hydrocortisone IT, and cytarabine IT on days 1, 3, and 5; and leucovorin calcium PO BID on days 2 and 4. Patients are randomized to 1 of 2 treatment arms. Arm III (R-COPADM induction therapy): Patients receive rituximab IV on days -2 (course 1) and 1; vincristine sulfate IV on day 1; prednisone PO or methylprednisolone IV on days 1-5; high-dose methotrexate IV over 4 hours* on day 1; leucovorin calcium PO every 6 hours on days 2-4; cyclophosphamide IV over 15 minutes on days 2-4; doxorubicin hydrochloride IV on day 2; and methotrexate IT, hydrocortisone IT, and cytarabine IT on days 2, 4, and 6. Treatment repeats every 21 days for 2 courses. NOTE: *During the second course, patients with CSF-positive disease receive high-dose methotrexate IV over 24 hours (instead of 4 hours). Consolidation therapy (R-COPADM): Patients receive rituximab IV on day 1; hydrocortisone IT and methotrexate IT on day 1; cytarabine IV over 12 hours on days 1-5; high-dose cytarabine IV over 3 hours on day 2-5; and etoposide IV over 2 hours on days 2-5. If CSF-positive, patients receive high-dose methotrexate IV over 24 hours on day 18, methotrexate IT, hydrocortisone IT, and cytarabine IT on day 19, and leucovorin calcium PO every 6 hours on days 19-21. Treatment repeats every 21 days for 2 courses. Maintenance therapy (R-COPADM): Patients receive vincristine sulfate IV on day 1; prednisone PO or methylprednisolone IV on days 1-5; high-dose methotrexate IV over 4 hours on day 1; leucovorin calcium PO every 6 hours on days 2-4; cyclophosphamide IV over 15 minutes on days 2-3; doxorubicin hydrochloride over 1 hour on day 2; and methotrexate IT, hydrocortisone IT, and cytarabine IT on day 2. Beginning 28 days later, patients receive cytarabine subcutaneously (SC) every 12 hours on days 1-5 and etoposide IV over 90 minutes on days 1-3. Arm IV (COPADM induction therapy): Patients receive vincristine sulfate, prednisone or methylprednisolone, high-dose methotrexate*, leucovorin calcium, cyclophosphamide, doxorubicin hydrochloride, and methotrexate, hydrocortisone, and cytarabine IT as in arm III. NOTE: *Patients with CSF-positive disease receive high-dose methotrexate IV over 24 hours (instead of 4 hours). Consolidation therapy (COPADM): Patients receive hydrocortisone and methotrexate IT, cytarabine, high-dose cytarabine, and etoposide as in arm III consolidation therapy. Maintenance therapy (COPADM): Patients receive vincristine sulfate, prednisone or methylprednisolone, high-dose methotrexate*, leucovorin calcium, cyclophosphamide, doxorubicin hydrochloride, methotrexate IT, hydrocortisone IT, cytarabine IT, cytarabine SC, and etoposide as in arm III maintenance therapy. NOTE: *Patients with CSF-positive disease receive high-dose methotrexate IV over 24 hours. Blood and tumor tissue samples are collected at baseline, during, and at the completion of study therapy for correlative studies. After completion of study treatment, patients are followed-up for 5 years.

    NCT ID:

    NCT01595048

    IRB Number:

    12-005148

    Who can I contact for additional information about this study?

    Rochester: Paul J. Galardy 507-538-7623
                        


  9. A Study to Evaluate the Efficacy and Safety of Lenalidomide as Maintenance Therapy for Patients With B-Cell CLL Following Second Line Therapy (THE CONTINUUM TRIAL)

    Jacksonville, Fla. View Summary

    A Study to Evaluate the Efficacy and Safety of Lenalidomide as Maintenance Therapy for Patients With B-Cell CLL Following Second Line Therapy (THE CONTINUUM TRIAL)

    Location:

    Jacksonville, Fla.

    Trial status:

    Open for Enrollment

    Why is this study being done?

    The purpose of this study is to determine if lenalidomide (Revlimid®) is safe and effective as a maintenance therapy at improving further the quality of the response you achieved with your last therapy and at prolonging the duration of your response.  This study will compare the effects (good and bad) of lenalidomide with the dummy drug.

    NCT ID:

    NCT00774345

    IRB Number:

    08-007040 13-000616

    Who can I contact for additional information about this study?

    - Mayo Clinic Cancer Center -
      Phone: 507-538-7623

    - Research Volunteer Program -
      Phone: 1-800-664-4542 (toll-free)
      Email: clinicaltrials@mayo.edu

    - International Research -
      Phone: 507-284-8884
      Email: intl.mcr@mayo.edu
  10. A Phase III Randomized Trial for Newly Diagnosed High Risk B-Lymphoblastic Leukemia (B-ALL) Testing Clofarabine (IND# 73789, NSC# 606869) in the Very High Risk Stratum

    Rochester, Minn. View Summary

    A Phase III Randomized Trial for Newly Diagnosed High Risk B-Lymphoblastic Leukemia (B-ALL) Testing Clofarabine (IND# 73789, NSC# 606869) in the Very High Risk Stratum

    Location:

    Rochester, Minn.

    Trial status:

    Open for Enrollment

    Why is this study being done?

    PRIMARY OBJECTIVES: I. To determine if the administration of post-Induction age-adjusted intrathecal triple therapy (ITT) on a Modified Berlin-Frankfurt-Munster (MBFM) interim maintenance (IM) high-dose methotrexate (IMHDM) backbone will improve 5-year disease-free survival (DFS) of children with high-risk (HR) acute lymphoblastic leukemia (ALL) compared to age-adjusted intrathecal (IT) methotrexate (MTX). II. To determine, in a randomized fashion, if the cyclophosphamide + etoposide-containing regimen (Experimental Arm 1) or the clofarabine + cyclophosphamide + etoposide-combination regimen (Experimental Arm 2) will improve the 4-year DFS of children, adolescents, and young adults with very high-risk (VHR) ALL compared to a modified MBFM-IMHDM regimen that contains a second IM (Control Arm). III. To determine, in a randomized fashion, if the cyclophosphamide + etoposide + clofarabine-containing combination regimen (Experimental Arm 2) will improve the 4-year DFS of children, adolescents, and young adults with VHR-ALL compared to the cyclophosphamide + etoposide combination regimen (Experimental Arm 1). SECONDARY OBJECTIVES: I. To determine the toxicity and tolerability of post-Induction age-adjusted ITT compared to age-adjusted IT MTX in children with HR-ALL. II. To determine the toxicity and tolerability of Experimental Arms 1 and 2 compared to the Control Arm in children, adolescents, and young adults with VHR-ALL. III. To determine whether a single-arm, modified Induction with limited anthracycline exposure and post-Induction therapy regimen with MBFM-IMIDM and reduced vincristine/steroid pulse frequency and enhanced supportive care in children with Down syndrome (DS) and HR-ALL will result in a >= 65% 5-year DFS and < 10% Induction mortality, and to gather clinical and biologic data that will facilitate further study to improve outcomes for this biologically and clinically unique patient subgroup. IV. To determine the toxicity and tolerability of MBFM-IMIDM in children with DS and HR-ALL. V. To determine if the reduction of minimal-residual disease (MRD) from end-Induction to end-Consolidation is greater for children, adolescents, and young adults with VHR-ALL receiving Experimental Arms 1 and/or 2 compared to the Control Arm. VI. To estimate overall survival (OS) rates both overall and by regimen for HR-ALL and VHR-ALL patients. VII. To determine if peripheral blood absolute lymphocyte count (ALC) at day 29 of Induction is predictive of DFS in children, adolescents, and young adults with HR-ALL. VIII. To determine the incidence and prognostic significance of recently discovered recurrent genomic lesions, including high cytokine receptor-like factor 2 (CRLF2) expression, CRLF2-activating genomic lesions, janus kinase (JAK) mutations, and IKAROS family zinc finger 1 (Ikaros) (IKZF1) mutations/deletions, in patients treated on this trial. IX. To determine the prognostic significance of molecular risk classifiers using Low Density Array (LDA) Taqman cards. X. To define the frequency of occurrence of key adverse events across all patient subgroups of HR-ALL in order to provide data for linked correlative biology studies that seek to develop biomarkers predictive of patients at risk for such events, including the following specific events: Grade 2 or higher (CNS hemorrhage, pancreatitis, osteonecrosis [ON], and seizure), Grade 3 or higher (GI bleed, encephalopathy, neuropathy, allergic reaction, ileus, mucositis/stomatitis, hyperbilirubinemia, and thrombosis), and all grades (transient ischemic attacks, strokes). XI. To define the differences in the burden of therapy between HR-ALL and VHR-ALL when treated on the various arms of this study by collecting and comparing the total number of days admitted to the hospital. XII. To determine the incidence of ON, defined by magnetic resonance (MR) imaging, and to characterize the natural history of clinically silent ON in children, adolescents, and young adults 10 years of age and greater and to assess the role of drugs (i.e., asparaginase and methotrexate) in addition to corticosteroids, in the risk for development of ON. XIII. To determine if the prevalence of cognitive deficits measured by CogState, in children (ages 6 to 11 years) with HR- and VHR-ALL at 1 year off therapy, is significantly higher than the normative population (> 14%) in the following domains: working memory, executive function, visual motor, processing speed, and visual attention. XIV. To compare the drug delivery of vincristine, pegaspargase, and methotrexate during Induction, Consolidation, Delayed Intensification, and Interim Maintenance II in 16-30 year olds treated on the control arm of the VHR study to that of adolescents and young adults (AYAs) with ALL treated with the same therapy on the C10403 adult cooperative group trial. OUTLINE: This is a multicenter study. Patients are stratified according to Down syndrome (no vs yes). Induction therapy for ALL patients without Down syndrome (35 days): Patients receive induction chemotherapy comprising cytarabine intrathecally (IT) on day 1; vincristine sulfate intravenously (IV) over 1 minute on days 1, 8, 15, and 22; daunorubicin hydrochloride IV over 1-15 minutes on days 1, 8, 15, and 22; dexamethasone orally (PO) or IV twice daily (BID) on days 1-14 (patients under 10 years old) or prednisone PO or IV BID on days 1-28 (patients at least 10 years old); pegaspargase IV over 1-2 hours on day 4; and methotrexate IT on days 8 and 29 (plus days 15 and 22 for CNS3). Patients are stratified according to National Cancer Institute (NCI) ALL risk criteria (high-risk or standard-risk vs very high-risk). High-risk or standard-risk ALL: Patients are randomized to 1 of 2 treatment arms. Consolidation therapy (56 days): Arm I HR-ALL C: Patients receive consolidation therapy comprising cyclophosphamide IV over 30-60 minutes on days 1 and 29; cytarabine IV or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO on days 1-4 and 29-42, methotrexate IT on days 1, 8, 15, and 22; vincristine sulfate IV over 1 minute on days 15, 22, 43, and 50; and pegaspargase IV over 1-2 hours on days 15 and 43. Patients with continuing clinical evidence of testicular leukemia undergo radiotherapy (RT) once daily, 5 days a week, for approximately 2½ weeks (12 fractions total). Arm II HR-ALL C: Patients receive intrathecal triple therapy (ITT) comprising methotrexate, hydrocortisone sodium succinate, and cytarabine on days 1, 8, 15, and 22. Patients also receive consolidation therapy as patients in arm I HR-ALL C. Patients with testicular leukemia also undergo RT as in arm I HR-ALL C. Interim maintenance therapy (63 days): Arm I HR-ALL IM: Patients receive interim maintenance (IM) therapy comprising vincristine sulfate IV over 1 minute on days 1, 15, 29, and 43; high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43; leucovorin calcium PO or IV on days 3-4, 17-18, 31-32, and 45-46; methotrexate IT on days 1 and 29; and mercaptopurine PO on days 1-56. Arm II HR-ALL IM: Patients receive ITT on days 1 and 29 and IM therapy as in arm I HR-ALL IM. Delayed intensification therapy (56 days): Arm I HR-ALL DI: Patients receive delayed intensification (DI) therapy comprising vincristine sulfate IV over 1 hour on days 1, 8, 15, 43, and 50; dexamethasone PO or IV BID on days 1-7 and 15-21; doxorubicin hydrochloride IV over 1-15 minutes on days 1, 8, and 15; methotrexate IT on days 1, 29, and 36; pegaspargase IV over 1-2 hours on days 4 and 43; cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; and thioguanine PO on days 29-42. Arm II HR-ALL DI: Patients receive ITT on days 1, 29, and 36 and DI therapy as in arm I HR-ALL DI. Maintenance therapy: Arm I HR-ALL M: Patients receive maintenance therapy comprising vincristine sulfate IV over 1 minute on days 1, 29, and 57; methotrexate IT on days 1 (also day 29 of courses 1-4) ; prednisone PO BID or IV on days 1-5, 29-33, and 57-61; mercaptopurine PO on days 1-84; and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicity. Arm II HR-ALL M: Patients receive ITT on day 1 (also day 29 of courses 1-4) and maintenance therapy as in arm I HR-ALL M. Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicity. Very high-risk ALL: Patients are randomized to 1 of 3 treatment arms. Consolidation therapy part 1 (days 1-28): In all arms, patients receive cyclophosphamide IV over 30-60 minutes on day 1; cytarabine IV or SC on days 1-4 and 8-11; mercaptopurine PO on days 1-14; methotrexate IT on days 1, 8, 15, and 22 (days 1 and 8 only for CNS patients): vincristine sulfate IV over 1 minute on days 15 and 22; and pegaspargase IV over 1-2 hours on day 15. Patients with continuing clinical evidence of testicular leukemia undergo RT once daily, 5 days a week, for approximately 2½ weeks (12 fractions total). Consolidation therapy part 2 (days 29-57): Arm A VHR-ALL C: Patients receive consolidation therapy comprising cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV over 15-30 minutes or SC on days 29-32 and 36-39; mercaptopurine PO on days 29-42; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Arm B VHR-ALL C: Patients receive consolidation therapy comprising cyclophosphamide IV over 15-30 minutes on days 29-33; etoposide IV over 1-2 hours on days 29-33; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Arm C VHR-ALL C: Patients receive clofarabine IV over 2 hours on days 29-33 and consolidation therapy as in arm B VHR-ALL C. Interim Maintenance I (63 days): In all arms, patients receive vincristine sulfate IV over 1 minute on days 1, 15, 29, and 43; high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43; leucovorin calcium PO or IV on days 3-4, 17-18, 31-32, and 45-46; mercaptopurine PO on days 1-56; and methotrexate IT on days 1 and 29. Delayed Intensification part 1 (days 1-28): In all arms, patients receive vincristine sulfate IV over 1 minute on days 1, 8, and 15; dexamethasone PO or IV BID on days 1-7 and 15-21; doxorubicin hydrochloride IV over 1-15 minutes on days 1, 8, and 15; methotrexate IT on day 1; and pegaspargase IV over 1-2 hours on day 4. Delayed Intensification part 2 (days 29-57): Arm A VHR-ALL DI: Patients receive DI therapy comprising cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV over 15-30 minutes or SC on days 29-32 and 36-39; thioguanine PO on days 29-42; methotrexate IT on days 29 and 36; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Arm B VHR-ALL DI: Patients receive DI therapy comprising cyclophosphamide IV over 15-30 minutes on days 29-33; etoposide IV over 1-2 hours on days 29-33; methotrexate IT on days 29 and 36; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Arm C VHR-ALL DI: Patients receive clofarabine IV over 2 hours on days 29-33 and DI therapy as in arm II B VHR-ALL DI. Interim Maintenance II (56 days): In all arms, patients receive vincristine sulfate IV over 1 minute and methotrexate IV on days 1, 11, 21, 31, and 41; pegaspargase IV over 1-2 hours on days 2 and 22; and methotrexate IT on days 1 and 31. Maintenance therapy: Patients with CNS3 disease at diagnosis undergo RT once daily over 4 weeks (10 fractions total). In all arms, patients receive vincristine sulfate IV over 1 minute on days 1, 29, and 57; prednisone PO BID on days 1-5, 29-33, and 57-61; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (except on methotrexate IT days); mercaptopurine PO on days 1-84; methotrexate IT on day 1 (also day 29 of courses 1 and 2 for CNS patients who did not receive RT). Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicities. High-risk ALL patients with Down syndrome: Patients are stratified according to response to induction therapy (days 1-14) (rapid early responders [RER; M1 day 15 bone marrow] vs slow early responders [SER; M2/M3 day 15 bone marrow]). Induction therapy (days 1-14): All patients receive cytarabine IT on day 1; vincristine sulfate IV over 1 minute on days 1 and 8, dexamethasone PO or IV BID (patients under 10 years old) or prednisone PO BID (patients at least 10 years old) on days 1-14, pegaspargase IV over 1-2 hours on day 4; methotrexate IT on day 8; and leucovorin calcium PO on days 10-11. Induction therapy (day 15-29): RER patients receive induction therapy comprising vincristine sulfate IV over 1 minute on days 15 and 22; dexamethasone PO BID or prednisone PO BID on days 15-28; methotrexate IT on day 29 (also days 15 and 22 for CNS3 patients); and leucovorin calcium PO on days 31-32 (also days 17-18 and 24-25 for CNS3 patients). SER patients receive daunorubicin hydrochloride IV over 1-15 minutes on day 15 and induction therapy as RER patients. Consolidation therapy (56 days): All patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29; cytarabine IV over 1-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO on days 1-14 and 29-42; vincristine sulfate IV over 1 minute on days 15, 22, 43, and 50; pegaspargase IV over 1-2 hours on days 15 and 43; methotrexate IT on days 1, 8, 15, and 22; and leucovorin calcium PO on days 3-4, 10-11, 17-18, and 24-25. Patients with continuing clinical evidence of testicular leukemia undergo RT once daily, 5 days a week, for approximately 2½ weeks (12 fractions total). Interim maintenance therapy (63 days): Patients receive vincristine sulfate IV over 1 minute on days 1, 15, 29, and 43; methotrexate IV over 24 hours on days 1, 15, 29, and 43; leucovorin calcium PO or IV on days 3-4, 17-18, 31-32, and 45-46; mercaptopurine PO on days 1-56; and methotrexate IT on days 1 and 29. Delayed intensification therapy: Patients receive vincristine sulfate IV over 1 minute on days 1, 8, 15, 43, and 50; dexamethasone PO BID on days 1-7 and 15-21; doxorubicin hydrochloride IV over 1-15 minutes on days 1, 8, and 15; pegaspargase IV over 1-2 hours on days 4 and 43; cyclophosphamide IV over 30-60 minutes on day 29; thioguanine PO on days 29-42; cytarabine IV over 15-30 minutes or SC on days 29-32 and 36-39; methotrexate IT on days 1, 29, and 36; and leucovorin calcium PO on days 3-4, 31-32 and 38-39. Maintenance therapy: Patients with CNS3 disease undergo RT once daily, 5 days a week, for 2 weeks (10 fractions total). Patients receive vincristine sulfate IV over 1 minute on day 1; prednisone PO BID or IV on days 1-5; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and methotrexate IT on day 1 (also day 29 of courses 1-4 for CNS3 patients who did not receive RT). Treatment repeats every 12 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo peripheral blood and bone marrow collection for correlative studies. Patients who are at least 10 years old have MRIs during Consolidation, Maintenance, and End of therapy and blood draws during Consolidation, Delayed Intensification, and Interim Maintenance II (VHR-ALL only). Patients may also undergo neurocognitive assessment during consolidation therapy, periodically during maintenance therapy, and at 1 year after completion of study therapy. After completion of study therapy, patients are followed up periodically for 10 years.

    NCT ID:

    NCT01406756

    IRB Number:

    11-007833

    Who can I contact for additional information about this study?

    Rochester: Carola A. Arndt 507-538-7623
                        


  1. 1
  2. 2
  3. 3
  4. 4
  5. 5
  6. Next