Clofarabine, Cyclophosphamide and Etoposide for Minimal Residual Disease Positive Acute Leukemia

NCT ID: NCT01677949

Last Updated: 2017-12-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2013-12-31

Study Completion Date

2016-01-31

Brief Summary

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Study Design:

This is a two-stage Phase II trial investigating the efficacy of Clofarabine, Cyclophosphamide and Etoposide in acute leukemia patients with detectable minimal residual disease (MRD) prior to allo-HCT. The primary objective is to determine the impact of the study treatment in eliminating the presence of minimal residual disease without causing a significant delay of allo-HCT due to treatment related toxicity. The intent of this study is to allow patients to proceed to transplant (independent of this study) within 42 days of Day 1 of Clofarabine based therapy.

Detailed Description

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Patients will be stratified at the time of enrollment based on diagnosis (ALL versus AML). Based on this two-stage optimal design, a maximum of 49 patients with ALL and a maximum of 49 patients with AML will be needed. For each disease cohort, 21 patients will be enrolled in stage 1. If at the end of stage 1, the criteria is met for activating stage 2 (based on success of clearing MRD, proceeding to transplant within 42 days and without excessive toxicity) for one or both groups, stage 2 will be activated with an additional 28 patients enrolled.

Conditions

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Acute Myeloid Leukemia Acute Lymphoblastic Leukemia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ALL patients receiving transplant

Patients intent on receiving an allogeneic hematopoietic cell transplantation (allo-HCT) with the diagnosis of acute lymphoblastic leukemia (ALL) along with Clofarabine, Etoposide and Cyclophosphamide.

Group Type EXPERIMENTAL

Clofarabine

Intervention Type DRUG

Days 1-5: Clofarabine 30 mg/m\^2 for 0-30 years of age or 20 mg/m\^2 for \> 30 years of age intravenously (IV) over 2 hours

Etoposide

Intervention Type DRUG

Days 1-5: Etoposide 100mg/m\^2 IV over 2 hours

Cyclophosphamide

Intervention Type DRUG

Days 1-5: Cyclophosphamide 300 mg/m\^2 as a 30-60 minute infusion

allogeneic hematopoietic cell transplantation

Intervention Type BIOLOGICAL

Between Days 28 and 42: infused independent of this study

AML patients receiving transplant

Patients intent on receiving an allogeneic hematopoietic cell transplantation (allo-HCT) with the diagnosis of acute myeloid leukemia (AML) along with Clofarabine, Etoposide and Cyclophosphamide.

Group Type EXPERIMENTAL

Clofarabine

Intervention Type DRUG

Days 1-5: Clofarabine 30 mg/m\^2 for 0-30 years of age or 20 mg/m\^2 for \> 30 years of age intravenously (IV) over 2 hours

Etoposide

Intervention Type DRUG

Days 1-5: Etoposide 100mg/m\^2 IV over 2 hours

Cyclophosphamide

Intervention Type DRUG

Days 1-5: Cyclophosphamide 300 mg/m\^2 as a 30-60 minute infusion

allogeneic hematopoietic cell transplantation

Intervention Type BIOLOGICAL

Between Days 28 and 42: infused independent of this study

Interventions

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Clofarabine

Days 1-5: Clofarabine 30 mg/m\^2 for 0-30 years of age or 20 mg/m\^2 for \> 30 years of age intravenously (IV) over 2 hours

Intervention Type DRUG

Etoposide

Days 1-5: Etoposide 100mg/m\^2 IV over 2 hours

Intervention Type DRUG

Cyclophosphamide

Days 1-5: Cyclophosphamide 300 mg/m\^2 as a 30-60 minute infusion

Intervention Type DRUG

allogeneic hematopoietic cell transplantation

Between Days 28 and 42: infused independent of this study

Intervention Type BIOLOGICAL

Other Intervention Names

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Clolar Eposin Etopophos Vepesid VP-16 Cytoxan allo-HCT

Eligibility Criteria

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Inclusion Criteria

* Diagnosis of acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) with \<5% blasts in the bone marrow (M1) by morphology and that meets one of the following criteria:

* Flow cytometric evidence of MRD (≥ 0.1% leukemic blasts for ALL or \<5% leukemic blasts for AML detected in the bone marrow) OR
* Molecular/cytogenetic evidence of disease (FISH or PCR methodology) performed within 7 days
* AND with the intent of going on to an allogeneic hematopoietic cell transplantation (allo-HCT) independent of this study
* Age 0 to 60 years
* Karnofsky Performance Status ≥ 50% for patients 16 years and older and Lansky Play Score ≥ 50 for patients under 16 years of age
* Patients must have a life expectancy ≥ 8 weeks as determined by the enrolling investigator
* Have acceptable organ function as defined within 7 days of study registration:

* Renal: creatinine clearance ≥70mL/min/1.73m2 or serum creatinine based on age/gender
* Hepatic: aspartate aminotransferase (ALT) \< 5 x upper limit of normal (ULN) and total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age
* Cardiac: left ventricular ejection fraction ≥ 40% by echocardiogram (ECHO/MUGA)
* Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. At least 14 days must have elapsed from prior chemotherapy; at least 7 days must have elapsed since receiving biological therapy.

Hematopoietic growth factors: At least 7 days since the completion of therapy with a growth factor and at least 14 days since pegfilgrastim (Neulasta®) administration.

* Sexually active females of child bearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device \[IUD\], surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of treatment and for 2 months after the last dose of chemotherapy. Sexually active men must agree to use barrier contraceptive for the duration of treatment and for 2 months after the last dose of chemotherapy.
* Voluntary written consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care

Exclusion Criteria

* Acute Promyelocytic Leukemia (APL)
* Active central nervous system (CNS) leukemia or known chloromatous disease
* Receiving or plans to receive concomitant chemotherapy, radiation therapy; immunotherapy or other anti-cancer therapy other than is specified in the protocol
* Systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)
* Pregnant or lactating. The agents used in this study are known to be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy.
* Known allergy to any of the agents or their ingredients used in this study
Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael Burke, M.D.

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

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Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Countries

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United States

Other Identifiers

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HM2012-05

Identifier Type: OTHER

Identifier Source: secondary_id

2011LS158

Identifier Type: -

Identifier Source: org_study_id