Bendamustine Hydrochloride, Clofarabine, and Etoposide in Treating Younger Patients With Relapsed or Refractory Hematologic Malignancies

NCT ID: NCT01900509

Last Updated: 2017-03-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2016-05-31

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.

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.

SECONDARY OBJECTIVES

• To estimate event-free survival at 4 months.
• To estimate minimal residual disease (MRD) levels present at end of each cycle of therapy in participants with leukemia.
• To characterize the pharmacokinetic profile of bendamustine in the proposed regimen.

Detailed Description

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.

Conditions

Hodgkin Lymphoma; Non-Hodgkin Lymphoma; Acute Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

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

INTERVENTIONS: bendamustine, clofarabine, etoposide (or etoposide phosphate), dexamethasone.

Group Type: EXPERIMENTAL

Bendamustine

Intervention Type: DRUG

Route of administration: intravenously (IV) over approximately 60 minutes, days 1-5.

Clofarabine

Intervention Type: DRUG

Route of administration: IV days 1-5.

Etoposide

Intervention Type: DRUG

Route of administration: IV days 1-5.

Etoposide phosphate

Intervention Type: DRUG

Route of administration: Used in substitution for etoposide in participants who experience allergic reaction, Etopophos® will be administered IV.

Dexamethasone

Intervention Type: DRUG

Route of administration: three times daily orally (by mouth), days 1-5.

Interventions

Bendamustine

Route of administration: intravenously (IV) over approximately 60 minutes, days 1-5.

Intervention Type: DRUG

Clofarabine

Route of administration: IV days 1-5.

Intervention Type: DRUG

Etoposide

Route of administration: IV days 1-5.

Intervention Type: DRUG

Etoposide phosphate

Route of administration: Used in substitution for etoposide in participants who experience allergic reaction, Etopophos® will be administered IV.

Intervention Type: DRUG

Dexamethasone

Route of administration: three times daily orally (by mouth), days 1-5.

Intervention Type: DRUG

Other Intervention Names

Treanda(R); Bendamustine hydrochloride; Clolar(TM); Clofarex; VP-16; Vepesid(R); Etopophos(R); Decadron(R)

Eligibility Criteria

Inclusion Criteria

• Participants with Hodgkin or Non-Hodgkin lymphoma must meet one of the following criteria: (a) Relapsing disease in 2nd or greater relapse and measurable disease, or (b) 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: (a) Relapsing acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), or acute biphenotypic leukemia in 2nd or greater relapse; or (b) 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: (a) Direct bilirubin ≤ upper limit of normal (ULN) for age, or if total bilirubin is > ULN, direct bilirubin is ≤ 1.4 mg/dl, and (b) 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: (a) Absolute neutrophil count (ANC) ≥ 1,000/µL, and (b) 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.

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Teva Pharmaceuticals USA

INDUSTRY

Sponsor Role: collaborator

St. Jude Children's Research Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sima Jeha, MD

Role: PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Locations

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Countries

United States

References

Jeha S, Crews KR, Pei D, Peyton M, Panetta JC, Ribeiro RC, Zhao X, Campbell P, Metzger ML, Yang JJ, Cheng C, Pui CH, Bhojwani D. Phase 1 study of bendamustine in combination with clofarabine, etoposide, and dexamethasone in pediatric patients with relapsed or refractory hematologic malignancies. Cancer. 2021 Jun 15;127(12):2074-2082. doi: 10.1002/cncr.33465. Epub 2021 Feb 17.

Reference Type: DERIVED

PMID: 33598942 (View on PubMed)

Related Links

http://www.stjude.org

St. Jude Children's Research Hospital

http://www.stjude.org/protocols

Clinical Trials Open at St. Jude

Other Identifiers

TEVA ISS

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2013-01148

Identifier Type: REGISTRY

Identifier Source: secondary_id

BECHEM

Identifier Type: -

Identifier Source: org_study_id