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

Primary Purpose

Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia

Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Clofarabine
Etoposide
Cyclophosphamide
allogeneic hematopoietic cell transplantation
Sponsored by
Masonic Cancer Center, University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia

Eligibility Criteria

undefined - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Masonic Cancer Center, University of Minnesota

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

ALL patients receiving transplant

AML patients receiving transplant

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Number of Patients Unable to Proceed to Transplantation
The primary endpoint of this study will be to determine the impact of Clofarabine, Cyclophosphamide and Etoposide on the conversion to an minimal residual disease (MRD) negative state at day 30 (<0.01% leukemic blasts by flow cytometry) or day 42 if day 30 marrow is un-evaluable due to hypocellularity per RECIST criteria as well as the ability of patients to reach allo-HCT without significant delay due to study treatment related toxicity. Unable to proceed to transplant by Day 42 will be considered unacceptable.

Secondary Outcome Measures

Rate of Pre-Transplant Chemotherapy-Induced Aplasia
defined as greater than 42 days after infusion of chemotherapy
Rate of Infectious Complications
Treatment-Related Mortality After Transplant
In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.
Disease-Free Survival After Transplant
The length of time after treatment ends that a patient survives without any signs or symptoms of that cancer or any other type of cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works.
Rate of Leukemic Relapse After Transplant
The return of disease after its apparent recovery/cessation.

Full Information

First Posted
August 28, 2012
Last Updated
November 29, 2017
Sponsor
Masonic Cancer Center, University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT01677949
Brief Title
Clofarabine, Cyclophosphamide and Etoposide for Minimal Residual Disease Positive Acute Leukemia
Official Title
A Phase II Trial Investigating Clofarabine, Cyclophosphamide and Etoposide for Minimal Residual Disease Positive Acute Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
April 2016
Overall Recruitment Status
Withdrawn
Why Stopped
Slow accrual
Study Start Date
December 2013 (undefined)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
January 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Masonic Cancer Center, University of Minnesota

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ALL patients receiving transplant
Arm Type
Experimental
Arm Description
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.
Arm Title
AML patients receiving transplant
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Clofarabine
Other Intervention Name(s)
Clolar
Intervention Description
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
Intervention Name(s)
Etoposide
Other Intervention Name(s)
Eposin, Etopophos, Vepesid, VP-16
Intervention Description
Days 1-5: Etoposide 100mg/m^2 IV over 2 hours
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
Days 1-5: Cyclophosphamide 300 mg/m^2 as a 30-60 minute infusion
Intervention Type
Biological
Intervention Name(s)
allogeneic hematopoietic cell transplantation
Other Intervention Name(s)
allo-HCT
Intervention Description
Between Days 28 and 42: infused independent of this study
Primary Outcome Measure Information:
Title
Number of Patients Unable to Proceed to Transplantation
Description
The primary endpoint of this study will be to determine the impact of Clofarabine, Cyclophosphamide and Etoposide on the conversion to an minimal residual disease (MRD) negative state at day 30 (<0.01% leukemic blasts by flow cytometry) or day 42 if day 30 marrow is un-evaluable due to hypocellularity per RECIST criteria as well as the ability of patients to reach allo-HCT without significant delay due to study treatment related toxicity. Unable to proceed to transplant by Day 42 will be considered unacceptable.
Time Frame
Between Day 30 and Day 42
Secondary Outcome Measure Information:
Title
Rate of Pre-Transplant Chemotherapy-Induced Aplasia
Description
defined as greater than 42 days after infusion of chemotherapy
Time Frame
After Day 42
Title
Rate of Infectious Complications
Time Frame
Day 1 Through Day 30
Title
Treatment-Related Mortality After Transplant
Description
In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.
Time Frame
Day 100
Title
Disease-Free Survival After Transplant
Description
The length of time after treatment ends that a patient survives without any signs or symptoms of that cancer or any other type of cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works.
Time Frame
1 Year
Title
Rate of Leukemic Relapse After Transplant
Description
The return of disease after its apparent recovery/cessation.
Time Frame
Day 100

10. Eligibility

Sex
All
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Burke, M.D.
Organizational Affiliation
Masonic Cancer Center, University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
Masonic Cancer Center, University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States

12. IPD Sharing Statement

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

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