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

Phase 1

Completed

• Conditions: Non-Hodgkin Lymphoma; Acute Leukemia; Hodgkin Lymphoma
• Interventions: Drug: Bendamustine; Drug: Clofarabine; Drug: Etoposide; Drug: Etoposide phosphate; Drug: Dexamethasone

• Registration Number: NCT01900509
• Lead Sponsor: St. Jude Children's Research Hospital

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.

Study Timeline

• Study First Submitted: 2013-07-11
• Study First Submitted QC: 2013-07-11
• Study First Posted: 2013-07-16
• Study Start: 2013-08
• Primary Completion: 2016-05
• Study Completion: 2016-05
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-21
• Last Update Posted: 2017-03-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment	Etoposide phosphate	All participants who meet eligibility for this study will follow the same treatment regimen. INTERVENTIONS: bendamustine, clofarabine, etoposide (or etoposide phosphate), dexamethasone.
Treatment	Etoposide	All participants who meet eligibility for this study will follow the same treatment regimen. INTERVENTIONS: bendamustine, clofarabine, etoposide (or etoposide phosphate), dexamethasone.
Treatment	Clofarabine	All participants who meet eligibility for this study will follow the same treatment regimen. INTERVENTIONS: bendamustine, clofarabine, etoposide (or etoposide phosphate), dexamethasone.
Treatment	Bendamustine	All participants who meet eligibility for this study will follow the same treatment regimen. INTERVENTIONS: bendamustine, clofarabine, etoposide (or etoposide phosphate), dexamethasone.
Treatment	Dexamethasone	All participants who meet eligibility for this study will follow the same treatment regimen. INTERVENTIONS: bendamustine, clofarabine, etoposide (or etoposide phosphate), dexamethasone.

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose	Continually throughout the study (up to 3 months)	Establish MTD of bendamustine in combination with clofarabine and etoposide.
Dose limiting toxicities	Continually throughout the study (up to 3 months)	Characterize safety profile and DLTs of bendamustine in combination with clofarabine and etoposide

Secondary Outcome Measures

Name	Time	Method
Event free survival	4 months after the start of therapy for the last patient enrolled on the study	Event-free survival (EFS) time will be calculated from on therapy to any kind of failure or to last contact date for participants who are alive without any failure at the last contact date. The time to EFS will be set to 0 for participants who fail to achieve complete remission. Kaplan-Meier estimates of EFS curves will be computed, along with estimates of standard errors by the method of Peto. Four month EFS, as well as longer term survival rates (6 month and 1 year) will be estimated with 95% confidence intervals.
Proportion of leukemia participants with positive minimal residual disease	At end of each cycle of chemotherapy (approximately at 1 month and 2 months)	The prevalence of MRD at end of each cycle is defined as proportion of MRD positives; we will estimate these proportions with point and interval estimates.
Plasma concentration of bendamustine	Day 1 and day 5 of cycle 1 therapy	Plasma concentrations of bendamustine will be measured using an established LC-MS/MS assay. Bendamustine pharmacokinetic parameters such as Cmax, tmax, AUC (0-t), t1/2, and clearance will be estimated using population-based modeling techniques.

Trial Locations

Locations (1)

St. Jude Children's Research Hospital; 🇺🇸 Memphis, Tennessee, United States