Ascorbic Acid and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Lymphoma

Overview

About this study

This randomized phase II trial studies how well ascorbic acid and combination chemotherapy work in treating patients with lymphoma that has come back or does not respond to therapy. Ascorbic acid may make cancer cells more sensitive to chemotherapy. Drugs used in chemotherapy, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ascorbic acid and combination chemotherapy may work better at treating lymphoma.

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:

  • Age ≥ 18 years.
  • Biopsy-proven relapsed or refractory lymphomas. Relapsed is defined as a relapse that occurred after having a response to the last therapy that lasted > 6 months. Refractory is no response or relapse within 6 months. Previous biopsies < 6 months prior to treatment on this protocol will be acceptable.
  • NOTE:  Arms A/B – relapsed or refractory DLBCL within 24 months from the end of anthracycline-based therapy. No prior salvage therapy. Patients can have received radiation therapy as part of initial treatment but not specifically for relapse.
  • NOTE:  Arm C – patients include relapsed lymphoma patients of any type, other than those eligible for Arms A/B, for which the recommended treatment includes one of the platinum-based regimens in 3.14. Of note, relapsed double-hit high grade lymphoma patients and relapsed Hodgkin lymphoma patients will be enrolled in Arm C. There is no limit on the number of prior therapies for Arm C patients. The patient must be eligible for a platinum-based regimen and must not have received the same regimen in the past without responding. 
  • Measureable or assessable disease: Measureable disease is defined as measurable by CT (dedicated CT or the CT portion of a PET/CT) or MRI:
    • To be considered measureable, there must be at least one lesion that has a single diameter of ≥ 1.5 cm NOTE: Skin lesions can be used if the area is ≥ 1.5cm in at least one diameter and photographed with a ruler. Patients with assessable disease by PET are also eligible as long as the assessable disease is biopsy proven lymphoma.
  • Arms A/B – eligible for treatment with ifosfamide, carboplatin, and etoposide (± rituximab).
  • Arm C – Eligible for treatment with one of the following standard, every 3 week, platinum-based salvage regimens (with or without monoclonal antibody as appropriate for the disease):
    • ifosfamide/carboplatin/etoposide (ICE) or (RICE);
    • cisplatin, cytosine arabinoside, dexamethasone (DHAP) or RDHAP;
    • gemcitabine, dexamethasone, cisplatin (GDP) or RGDP;
    • gemcitabine and oxaliplatin (GemOx) or RGemOx;
    • Oxaliplatin, cytosine arabinoside, dexamethasone (OAD) or ROAD.
  • ECOG Performance Status (PS) 0, 1 or 2.
  • The following laboratory values obtained ≤ 14 days prior to registration (except creatinine which needs to be obtained ≤ 7 days prior to registration):
    • Hemoglobin ≥ 8.0 g/dL (may transfuse to meet this requirement);
    • Absolute neutrophil count (ANC) ≥ 1500/mm^3;
    • Platelet count ≥ 75000/mm^3;
    • Total bilirubin ≤ 2 x ULN (if >2 x ULN direct bilirubin is required and should be ≤ 1.5 x ULN);
    • Alanine aminotransferase (ALT) and Aspartate transaminase (AST) 3 x ULN (≤ 5 x ULN for patients with liver involvement);
    • Creatinine ≤ 1.6 mg/dL. If over 1.6, then the Calculated creatinine clearance must be ≥ 55 ml/min using the Cockcroft-Gault formula below:
      • Cockcroft-Gault Equation:
        • Creatinine clearance for males = (140 - age)(weight in kg)
        •                                                     (72)(serum creatinine in mg/dL)
        • Creatinine clearance for females =    (140 - age)(weight in kg)(0.85)
        •                                                     (72)(serum creatinine in mg/dL)
  • Negative pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only.
    • NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • HIV test done ≤ 14 days prior to registration:
    • If positive,the CD4 count must be > 400.
  • Provide written informed consent.
  • Willingness to have a central venous line (PICC or PORT).
  • Willingness to provide mandatory blood specimens for correlative research.
  • Willingness to provide mandatory tissue specimens for correlative research.
  • Willingness to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).
  • Willingness to follow the requirements of the intravenous ascorbic acid program schedule.

Exclusion Criteria:

  • Any of the following because this study involves:
    • an agent that has known genotoxic, mutagenic and teratogenic effects:
      • Pregnant persons;
      • Nursing persons;
      • Persons of childbearing potential who are unwilling to employ adequate contraception.
  • Any therapy ≤ 2 weeks prior to registration.
    • Exception: patients on ibrutinib or corticosteroids (any dose) may continue therapy up until the new regimen has started at investigator discretion. Corticosteroids can be tapered to lowest possible dose after start of treatment at investigator discretion. Palliative radiation is allowed.
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.   
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, pulmonary congestion or pulmonary edema, clinical dehydration, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Receiving any other investigational agent which would be considered as a treatment for the lymphoma.
  • Other active malignancy than lymphoma.
    • NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer that could interfere with this protocol therapy. Patients on hormonal therapy for treated breast or prostate cancer are permitted if they meet other eligibility criteria. Patients with non-melanotic skin cancer may enroll.
  • History of myocardial infarction ≤ 6 months, or current symptomatic congestive heart failure or LVEF < 40% or with > grade 2 diastolic dysfunction, with no symptoms or signs of heart failure.
  • Known G6PD (glucose-6-phosphate dehydrogenase) deficiency (below lower limit of normal).
  • Patients with active CNS lymphoma or active CSF involvement with malignant cells requiring CNS-specific therapy with IV or IT MTX.
    • NOTE: Patients with any prior CNS lymphoma (parenchymalor leptomeningeal) MUST be in CR in those compartments without any maintenance therapy required.
  • Patients with uncontrolled or symptomatic kidney stones.
    • NOTE: Patients with calcium oxalate crystals on baseline urinalysis or a history of symptomatic calcium oxalate stones must be seen or have an e-consult by the Nephrology Stone Clinic and placed on a low oxalate diet (< 100 mg oxalate/day) prior to enrollment.
  • Known paroxysmal nocturnal hemoglobinuria (PNH).

 

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

Thomas Witzig, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

La Crosse, Wis.

Mayo Clinic principal investigator

Jonathan Ticku, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Mankato, Minn.

Mayo Clinic principal investigator

Stephan Thome, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Eau Claire, Wis.

Mayo Clinic principal investigator

Eyad Al-Hattab, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

.
CLS-20399894

Mayo Clinic Footer