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

NCT01900509 | Completed Phase 1 FDA Drug

• 3 other identifiers: BECHEMTEVA ISSNCI-2013-01148
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 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. 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.

Conditions

Hodgkin Lymphoma; Non-Hodgkin Lymphoma; Acute Leukemia

Keywords

Childhood leukemia; Childhood lymphoma; Bendamustine

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose

  Establish MTD of bendamustine in combination with clofarabine and etoposide.

  Continually throughout the study (up to 3 months)

• Dose limiting toxicities

  Characterize safety profile and DLTs of bendamustine in combination with clofarabine and etoposide

  Continually throughout the study (up to 3 months)

Secondary Outcomes (3)

• Event free survival

  4 months after the start of therapy for the last patient enrolled on the study

• Proportion of leukemia participants with positive minimal residual disease

  At end of each cycle of chemotherapy (approximately at 1 month and 2 months)

• Plasma concentration of bendamustine

  Day 1 and day 5 of cycle 1 therapy

Study Arms (1)

Treatment

EXPERIMENTAL

All participants who meet eligibility for this study will follow the same treatment regimen. INTERVENTIONS: bendamustine, clofarabine, etoposide (or etoposide phosphate), dexamethasone.

Drug: Bendamustine; Drug: Clofarabine; Drug: Etoposide; Drug: Etoposide phosphate; Drug: Dexamethasone

Interventions

Bendamustine DRUG

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

Also known as: Treanda(R), Bendamustine hydrochloride

Treatment

Clofarabine DRUG

Route of administration: IV days 1-5.

Also known as: Clolar(TM), Clofarex

Treatment

Etoposide DRUG

Route of administration: IV days 1-5.

Also known as: VP-16, Vepesid(R)

Treatment

Etoposide phosphate DRUG

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

Also known as: Etopophos(R)

Treatment

Dexamethasone DRUG

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

Also known as: Decadron(R)

Treatment

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• Teva Pharmaceuticals USA: collaborator

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Publications (1)

• 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.

  PMID: 33598942 DERIVED

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Hodgkin Disease; Lymphoma, Non-Hodgkin

Interventions

Bendamustine Hydrochloride; Clofarabine; Etoposide; etoposide phosphate; Dexamethasone

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Adenine Nucleotides; Purine Nucleotides; Purines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated

Study Officials

• Sima Jeha, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2013
• First Posted: July 16, 2013
• Study Start: August 1, 2013
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: March 22, 2017

Record last verified: 2017-03

Locations

US (1)