A Study to Investigate the Safety and Tolerability of REGN1979 in Patients With CD20+ B-Cell Malignancies

Overview

About this study

This is an open-label, multi-center, dose escalation study of REGN1979 administered as an IV (intravenous) infusion. This phase 1 study will investigate the safety and tolerability of REGN1979 in patients with Non-Hodgkin's Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL)

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Have documented CD20+ B-cell malignancy, with active disease not responsive to prior therapy, for whom no standard of care options exists, and for whom treatment with an anti-CD20 antibody may be appropriate:
    • B-NHL confirmed by NCI working group criteria, 2007 (Cheson 2007) (Appendix 2);
    • CLL confirmed by the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) working group criteria, 2008 (Hallek 2008) (Appendix 3).
  • Patients with small lymphocytic lymphoma (SLL) will be enrolled in the CLL arm and follow NHL assessments.
  • As of protocol amendment 16, enrollment is closed for CLL, FL grade 1-3a and aggressive lymphoma cohorts. The only cohort that remains open for enrollment is the DLBCL after failure of CAR-T therapy cohort.

 

  • NOTE: A patient with CD20-negative lymph node (NHL) biopsy performed as standard of care just prior to enrollment, remains eligible for the study provided the patient had previously documented CD20+ disease AND was previously treated with rituximab or other CD20-directed antibody therapy within approximately 6 months. Individual cases may be discussed with the medical monitor.
  • Patients with B-NHL must have had prior treatment with an anti-CD20 antibody therapy. Patients with CLL are not required to have received prior treatment with an anti-CD20 antibody therapy, provided the patient has failed either a BTK inhibitor or PI3K inhibitor and the treating physician deems it appropriate for the patient to be entered into a phase 1 trial. Refractory is defined as no response (SD/PD) or relapse within ≤6 months of last treatment. 
    • For inclusion in the FL grade 1-3a expansion cohort, patients must have received at least 2 prior lines of systemic therapy, including an anti-CD20 antibody and an alkylating agent; patients require failure of combination of lenalidomide plus rituximab where approved or not appropriate to receive this treatment according to the investigator. As of protocol amendment 16, enrollment is closed for patients with FL grade 1-3a;
    • For inclusion in the disease-specific expansion cohort enrolling DLBCL patients after failure of CAR-T therapy, the patient must have recovered from the toxicities of the lymphodepletion therapy and CAR-T infusion. There is no requirement for the prior CAR-T therapy to be the most recent line of therapy before study enrollment. Prior to enrollment, there must be verbal communication and documentation between the investigator and the medical monitor regarding prior toxicities associated with CAR-T therapy and their resolution;
    • Patients with aggressive lymphoma assigned to the aggressive lymphoma expansion cohort must have received at least one prior line of therapy consisting of an anti-CD20 antibody. Patients with prior CAR-T therapy will not be included in this cohort. As of protocol amendment 16, enrollment is closed for patients with aggressive lymphoma;
    • Patients with lymphoma eligible for the aggressive lymphoma expansion cohort include the following subtypes based on the WHO classification (Beham Schmid, 2017):
      • DLBCL not otherwise specified (NOS);
      • Germinal center B-cell type;
      • Activated B-cell type
      • Note: DLBCL includes both de novo DLBCL and transformed DLBCL arising from indolent lymphoma/CLL.
      • Primary mediastinal (thymic) large B-cell lymphoma;
      • T-cell/histiocyte-rich large B-cell lymphoma;
      • Epstein-Barr virus (EBV)+ DLBCL, NOS
      • High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements;
      • High-grade B-cell lymphoma, NOS;
      • B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma;
      • Follicular lymphoma, grade 3b.
  • New enrollment of patients with MCL will be paused as of protocol amendment 15 until further risk mitigation measures are put in place for this patient population.
  • All patients (B-cell NHL and CLL) must have at least one bi-dimensionally measurable lesion ≥ 1.5 cm on the longest diameter) documented by CT or MRI scan, if CT scan is not feasible.
  • Patients with CLL must have white blood cell (WBC) ≤ 200 x 10^9/L. As of protocol amendment 16, enrollment is closed for patients with CLL. 
  • Age ≥ 18 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
  • Life expectancy of at least 6 months.
  • Adequate bone marrow function documented by:
    • Platelet counts ≥ 75 x 10^9/L;
    • Hb level ≥ 9 g/dL;
    • ANC ≥ 1 x 10^9/L.
    • NOTE: Patients with cell counts below thresholds listed above may be considered for enrollment if, in the opinion of the investigator, the reason is believed to be due to bone marrow infiltration by underlying disease. In such cases,  the investigator must discuss the eligibility with the sponsor and receive approval for enrollment in writing.
  • Adequate organ function documented by:
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 X ULN;
    • Total bilirubin ≤ 1.5 X ULN;
    • NOTE: Patients with Gilbert’s syndrome do not need to meet this requirement provided their total bilirubin is unchanged from their baseline.
    • Calculated creatinine clearance by Cockcroft-Gault ≥ 50 mL/min.
    • NOTE: Patients may be considered for enrollment if, in the opinion of the investigator, the abnormal laboratory results are due to underlying disease. In such cases, the investigator must discuss the eligibility with the sponsor and receive approval for enrollment in writing.
    • NOTE: Patients with borderline creatinine clearance by Cockcroft-Gault may be considered for enrollment if a measured creatinine clearance (based on 24-hour urine or other reliable method) is ≥ 50 mL/min.
  • Willingness to undergo mandatory tumor biopsy pre-treatment, if in the opinion of the investigator, the patient has an accessible lesion that can be biopsied without significant risk to the patient.
  • Willing and able to comply with clinic visits and study-related procedures.
  • Provide signed informed consent.

Exclusion Criteria:

  • Primary central nervous system (CNS) lymphoma or known or suspected CNS involvement by non-primary CNS NHL.
  • History of or current relevant CNS pathology such as:
    • Epilepsy, seizure, paresis, aphasia, apoplexia, severe brain injuries, cerebellar disease, organic brain syndrome, psychosis; or
    • Evidence for presence of inflammatory lesions and/or vasculitis on cerebral MRI.
  • Standard anti-neoplastic chemotherapy (non-biologic) within 5-times the half-life or within 28 days, whichever is shorter, prior to first administration of study drug.
  • Standard radiotherapy within 14 days of first administration of study drug.
    • NOTE: Palliative radiotherapy to a symptomatic lymph node/lesion is allowed provided the irradiated lesion(s) or node(s) is not included as a target lesion for tumor assessments.
  • Allogeneic stem cell transplantation.
  • Treatment with rituximab, alemtuzumab, or other investigational or commercial biologic agent within 12 weeks prior to first administration of study drug.
    • NOTE: for patients with aggressive lymphoma for which immediate treatment is required, the wash-out period may be reduced to 28 days. This will require discussion with and approval by the sponsor in writing.
  • Immunosuppressive therapy (other than biologic) within 28 days of first administration of study drug.
  • Treatment with an investigational non-biologic agent within 28 days of first administration of study drug.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition of study drug.
  • History of hypersensitivity to any compound in the tetracycline antibiotics group.
  • Concurrent active malignancy for which the patient is receiving treatment.
  • Known active bacterial, viral, fungal, mycobacterial or other infection or any major episode of infection requiring hospitalization or treatment with IV anti-infectives within 4 weeks of first administration.
  • Evidence of significant concurrent disease or medical condition that could interfere with the conduct of the study, or put the patient at significant risk including, but not limited to, significant cardiovascular disease (e.g., New York Heart Association Class III or IV cardiac disease, myocardial infarction within the previous 6 months, unstable arrhythmias or unstable angina) and/or significant pulmonary disease (eg, obstructive pulmonary disease and history of symptomatic bronchospasm).
    • NOTE: Patients with a medical history of cardiac disease should be evaluated by ECHO or multi-gated acquisition scan (MUGA) prior to first administration of REGN1979 to ensure adequate cardiac reserves and function.
  • Ongoing systemic corticosteroid treatment, with the exception of corticosteroid use for other (non-tumor and non-immunosuppressive) indications up to a maximum of 10 mg/day of prednisone or equivalent.
  • Infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).  Patients with hepatitis B (HepBsAg+) who have controlled infection (serum hepatitis B virus DNA that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted upon consultation with the physician managing the infection.
  • Known hypersensitivity to both allopurinol and rasburicase.
  • Pregnant or breast-feeding women.
  • Women of childbearing potential* who are unwilling to practice highly effective contraception prior to the initial study drug treatment, during the study, and for at least 6 months after the last dose. Highly effective contraceptive measures include stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening; intrauterine device; intrauterine hormone-releasing system; bilateral tubal ligation; vasectomized partner; and or sexual abstinence†, ‡.
    • * Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of childbearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.
    • † Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient.
    • ‡ Periodic abstinence (calendar, symptothermal and post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method (LAM) are not acceptable methods of contraception. Female condom and male condom should not be used together.
  • Men who are unwilling to practice highly effective contraception prior to, during, and 6 months after the last dose.
  • Administration of live vaccination within 28 days of first administration of study drug.
  • Member of the clinical site study team and/or his/her immediate family, unless prior approval is granted by the Sponsor.

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Stephen Ansell, M.D., Ph.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available
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CLS-20152420

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