Bendamustine Hydrochloride, Clofarabine, and Etoposide in Treating Younger Patients With Relapsed or Refractory Hematologic Malignancies
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|ClinicalTrials.gov Identifier: NCT01900509|
Recruitment Status : Completed
First Posted : July 16, 2013
Last Update Posted : March 22, 2017
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.
- 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.
- 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.
|Condition or disease||Intervention/treatment||Phase|
|Hodgkin Lymphoma Non-Hodgkin Lymphoma Acute Leukemia||Drug: Bendamustine Drug: Clofarabine Drug: Etoposide Drug: Etoposide phosphate Drug: Dexamethasone||Phase 1|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||16 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Trial of Bendamustine in Combination With Clofarabine and Etoposide in Pediatric Patients With Relapsed or Refractory Hematologic Malignancies|
|Study Start Date :||August 2013|
|Actual Primary Completion Date :||May 2016|
|Actual Study Completion Date :||May 2016|
All participants who meet eligibility for this study will follow the same treatment regimen.
INTERVENTIONS: bendamustine, clofarabine, etoposide (or etoposide phosphate), dexamethasone.
Route of administration: intravenously (IV) over approximately 60 minutes, days 1-5.
Route of administration: IV days 1-5.
Route of administration: IV days 1-5.
Drug: Etoposide phosphate
Route of administration: Used in substitution for etoposide in participants who experience allergic reaction, Etopophos® will be administered IV.
Other Name: Etopophos(R)
Route of administration: three times daily orally (by mouth), days 1-5.
Other Name: Decadron(R)
- Maximum tolerated dose [ Time Frame: Continually throughout the study (up to 3 months) ]Establish MTD of bendamustine in combination with clofarabine and etoposide.
- Dose limiting toxicities [ Time Frame: Continually throughout the study (up to 3 months) ]Characterize safety profile and DLTs of bendamustine in combination with clofarabine and etoposide
- Event free survival [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01900509
|United States, Tennessee|
|St. Jude Children's Research Hospital|
|Memphis, Tennessee, United States, 38105|
|Principal Investigator:||Sima Jeha, MD||St. Jude Children's Research Hospital|