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Trial record 6 of 11 for:    "Childhood Leukemia" | "Dexamethasone acetate"

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
Sponsor:
Collaborator:
Teva Pharmaceuticals USA
Information provided by (Responsible Party):
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.

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

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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


Arm Intervention/treatment
Experimental: Treatment

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

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

Drug: Bendamustine
Route of administration: intravenously (IV) over approximately 60 minutes, days 1-5.
Other Names:
  • Treanda(R)
  • Bendamustine hydrochloride

Drug: Clofarabine
Route of administration: IV days 1-5.
Other Names:
  • Clolar(TM)
  • Clofarex

Drug: Etoposide
Route of administration: IV days 1-5.
Other Names:
  • VP-16
  • Vepesid(R)

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)

Drug: Dexamethasone
Route of administration: three times daily orally (by mouth), days 1-5.
Other Name: Decadron(R)




Primary Outcome Measures :
  1. Maximum tolerated dose [ Time Frame: Continually throughout the study (up to 3 months) ]
    Establish MTD of bendamustine in combination with clofarabine and etoposide.

  2. 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


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

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


Locations
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United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Sponsors and Collaborators
St. Jude Children's Research Hospital
Teva Pharmaceuticals USA
Investigators
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Principal Investigator: Sima Jeha, MD St. Jude Children's Research Hospital

Additional Information:
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Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT01900509     History of Changes
Other Study ID Numbers: BECHEM
TEVA ISS ( Other Identifier: Teva Pharmaceuticals )
NCI-2013-01148 ( Registry Identifier: NCI Clinical Trial Registration Program )
First Posted: July 16, 2013    Key Record Dates
Last Update Posted: March 22, 2017
Last Verified: March 2017

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by St. Jude Children's Research Hospital:
Childhood leukemia
Childhood lymphoma
Bendamustine

Additional relevant MeSH terms:
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Dexamethasone
Dexamethasone acetate
BB 1101
Lymphoma
Lymphoma, Non-Hodgkin
Hodgkin Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Etoposide
Etoposide phosphate
Bendamustine Hydrochloride
Clofarabine
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action