BECHEM: Bendamustine, Clofarabine and Etoposide in Treating Younger Patients with Relapsed or Refractory Hematologic Malignancies

A Phase I Trial of Bendamustine in Combination with Clofarabine and Etoposide in Pediatric Patients with Relapsed or Refractory Hematologic Malignancies

Categories:

Leukemia / Lymphoma

Phase I/II

Diseases Treated:

Relapsed or refractory hematologic malignancies

Eligibility Overview:

  • Diagnosis of Hodgkin lymphoma, non-Hodgkin lymphoma or leukemia that has come back or did not respond to treatment
  • Must be 21 years of age or younger at the time of enrollment
  • Must have adequate kidney and heart function 
  1. Brief Summary

    Participants with relapsed or refractory leukemia or lymphoma will be recruited for this study to find whether or not the addition of a new drug called bendamustine will be safe and possible to give with other chemotherapy drugs. This drug is approved by the Food and Drug Administration (FDA) for the treatment of other cancers in adults that are similar to those being studied in the research trial.

    Bendamustine will be combined with clofarabine and etoposide in a five-day cycle. Dexamethasone will be given to prevent capillary leak syndrome associated with clofarabine. If the participant does not develop progressive disease or a dose-limiting toxicity (DLT) during the first cycle, a second cycle may be administered as a bridge to transplant. Each cycle lasts 21-28 days (or until count recovery).

    Concomitant intrathecal therapy can be given at the investigator's discretion, but not on the same days as chemotherapy. Recommendations are triple intrathecal therapy (methotrexate, hydrocortisone, cytarabine) weekly for participants with CNS2 or CNS3 disease, and every two weeks for participants with CNS1 disease. Leucovorin may be given according to institutional guidelines.

    The intent of this study design is for all participants to receive and complete one course of therapy. Participants who exhibit signs of disease progression or experience an unacceptable toxicity will be discontinued from protocol treatment.

    Primary Objectives

    • To establish the maximum tolerated dose (MTD) of bendamustine in combination with clofarabine and etoposide in pediatric participants with hematologic malignancies
    • To characterize the safety profile and dose-limiting toxicities (DLTs) of bendamustine in combination with clofarabine and etoposide

    Study Arm

    Experimental: Treatment

    All participants who meet eligibility for this study will follow the same treatment regimen.

    Interventions

    Drugs: bendamustine, clofarabine, etoposide (or etoposide phosphate), dexamethasone

    Eligibility

    Inclusion Criteria:

    • Participants with Hodgkin or non-Hodgkin lymphoma must meet one of the following criteria:
      • Relapsing disease in 2nd or greater relapse and measurable disease, or
      • Refractory disease failing to achieve complete remission (CR) with > 2 induction or re-induction attempts
    • Participant with acute leukemia must meet one of the following criteria:
      • Relapsing acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) or acute biphenotypic leukemia in 2nd or greater relapse, or
      • Refractory ALL, AML, or acute biphenotypic leukemia failing to achieve CR with ≥ 2 induction or re-induction attempts
    • Participant with leukemia has M2 or M3 marrow at the time of enrollment. Participant with M2 marrow must have definite cytogenetic, molecular or immunophenotypic evidence of recurrent/refractory disease.
    • Age is ≤ 21 years (participant has not yet reached 22nd birthday).
    • Karnofsky or Lansky performance score is ≥ 60%. The Lansky performance score should be used for participants < 16 years and the Karnofsky performance score for participants ≥ 16 years.
    • There are no known contra-indications to any of the planned agents used in this protocol. Etoposide may be substituted by etoposide phosphate (etopophos) if the patient has a history of hypersensitivity reaction to etoposide.
    • Adequate renal function defined as:
      • glomerular filtration rate > 60 cc/min/1.73m2, or
      • normal serum creatinine based on age
    • Adequate hepatic function:
      • Direct bilirubin ≤ upper limit of normal (ULN) for age, or if total bilirubin is > ULN, direct bilirubin is ≤ 1.4 mg/dl, and
      • AST and ALT ≤ 5 x ULN for age
    • Adequate cardiac function defined as shortening fraction of ≥ 27% or ejection fraction ≥ 45%.
    • Lymphoma participants without bone marrow involvement must have:
      • Absolute neutrophil count (ANC) ≥ 1,000/µL, and
      • Platelet count > 50,000/mm^3 (without transfusion support). [Note: these criteria are waived for participants with leukemia or lymphoma participants with bone marrow involvement.]
    • Participant must have recovered from the acute side effects of all prior anti-cancer therapy, and :
      • At least 2 weeks have elapsed since prior systemic cytotoxic chemotherapy (except intrathecal chemotherapy, and/or low dose maintenance therapy such as vincristine, mercaptopurine, methotrexate or glucocorticoids), and
      • At least 4 weeks have elapsed since treatment with an investigational agent or antibody-based therapy, if applicable, and
      • If the participant received a prior allogeneic hematopoietic stem cell transplantation (HSCT), at least 3 months have elapsed and there is no evidence of active graft-versus-host disease (GVHD), participant has discontinued immunosuppression, and there is no history of veno-occlusive disease

    Exclusion Criteria:

    • Active, uncontrolled infection or severe concurrent medical disease, including but not limited to congestive heart failure, cardiac arrhythmias, or psychiatric illness
    • Isolated extramedullary disease (leukemia)
    • Primary CNS lymphoma
    • Pregnant or lactating (female participant of childbearing potential must have negative serum or urine pregnancy test required within 7 days prior to start of treatment)
    • Known HIV or active hepatitis B or C infection
    • Known hypersensitivity to bendamustine or mannitol

    Study Design

    • Endpoint Classification: Safety/Efficacy Study
    • Intervention Model: Single Group Assignment
    • Masking: Open Label
    • Primary Purpose: Treatment

     

  2. About this clinical trial

    BECHEM is a Phase I clinical trial for children with leukemia or lymphoma that has come back or did not respond to treatment. People who are not in a study are usually treated with FDA-approved chemotherapy and/or stem cell transplant, but right now, there are no treatments that are known to work well. For this reason, St. Jude is offering this clinical trial.

    In this study, St. Jude researchers want to find out whether or not adding a new drug called bendamustine will be safe and possible to give with other chemotherapy drugs when treating children who have leukemia or lymphoma that has come back or did not respond to treatment.

    Purpose of this clinical trial

    The main goal of this clinical trial is to find the highest dose of bendamustine that can be safely given to children in this study, when it is given in combination with two chemotherapy drugs called clofarabine and etoposide.

    Bendamustine is a drug approved by the FDA (Food and Drug Administration) for the treatment of chronic lymphocytic leukemia (CLL) and a slow-growing type of non-Hodgkin lymphoma.  Bendamustine has not been approved by the FDA to be used in children, and this drug has not been given together with the other drugs used in this study.

    Treatment

    Your child will receive strong chemotherapy drugs to kill leukemia or lymphoma cells and put your child’s cancer into remission (no signs or symptoms). Your child will also receive chemotherapy to stop leukemia or lymphoma cells from spreading to the spinal fluid or to treat the spinal fluid if cancer cells are present.

    Further treatment will depend on how your child’s leukemia or lymphoma responds to the study drugs.

    Eligibility overview

    • Diagnosis of Hodgkin lymphoma, non-Hodgkin lymphoma or leukemia that has come back or did not respond to treatment
    • Must be 21 years of age or younger at the time of enrollment
    • Must have adequate kidney and heart function
  3. BECHEM  Quick View
    Sponsor St. Jude Children's Research Hospital
    Collaborator Teva Pharmaceuticals USA
    Clinicaltrials.gov identifier NCT01900509
    Trial start date August 2013
    Estimated enrollment 30
    Study type Interventional
    Study phase Phase 1
    Conditions
    • Hodgkin Lymphoma
    • Non-Hodgkin Lymphoma
    • Acute Leukemia
    Ages Up to 21 years
    Principal investigator Sima Jeha, MD
    Study site St. Jude Children’s Research Hospital
    For a consultation or to discuss BECHEM St. Jude Physician/Patient Referral Office
    1-888-226-4343
    referralinfo@stjude.org
     

Contact

Sima Jeha, MD

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334
Email: referralinfo@stjude.org

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.