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

Information source: St. Jude Children's Research Hospital
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Hodgkin Lymphoma; Non-Hodgkin Lymphoma; Acute Leukemia

Intervention: Bendamustine (Drug); Clofarabine (Drug); Etoposide (Drug); Etoposide phosphate (Drug); Dexamethasone (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: St. Jude Children's Research Hospital

Official(s) and/or principal investigator(s):
Sima Jeha, MD, Principal Investigator, Affiliation: St. Jude Children's Research Hospital

Overall contact:
Sima Jeha, MD, Phone: 866-278, Ext: 5833, Email: info@stjude.org

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.

Clinical Details

Official title: A Phase I Trial of Bendamustine in Combination With Clofarabine and Etoposide in Pediatric Patients With Relapsed or Refractory Hematologic Malignancies

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

Primary outcome:

Maximum tolerated dose

Dose limiting toxicities

Secondary outcome:

Event free survival

Proportion of leukemia participants with positive minimal residual disease

Plasma concentration of bendamustine

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.

Eligibility

Minimum age: N/A. Maximum age: 21 Years. Gender(s): Both.

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.

Locations and Contacts

Sima Jeha, MD, Phone: 866-278, Ext: 5833, Email: info@stjude.org

St. Jude Children's Research Hospital, Memphis, Tennessee 38105, United States; Recruiting
Sima Jeha, MD, Phone: 866-278-5833, Email: info@stjude.org
Sima Jeha, MD, Principal Investigator
Additional Information

St. Jude Children's Research Hospital

Clinical Trials Open at St. Jude

Starting date: August 2013
Last updated: March 12, 2015

Page last updated: August 23, 2015

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