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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Masonic Cancer Center, University of Minnesota
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT01677949
First received: August 28, 2012
Last updated: July 8, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Drug: Clofarabine
Drug: Etoposide
Drug: Cyclophosphamide
Biological: allogeneic hematopoietic cell transplantation
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial Investigating Clofarabine, Cyclophosphamide and Etoposide for Minimal Residual Disease Positive Acute Leukemia

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Number of Patients Unable to Proceed to Transplantation [ Time Frame: Between Day 30 and Day 42 ] [ Designated as safety issue: No ]
    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 [ Time Frame: After Day 42 ] [ Designated as safety issue: No ]
    defined as greater than 42 days after infusion of chemotherapy

  • Rate of Infectious Complications [ Time Frame: Day 1 Through Day 30 ] [ Designated as safety issue: Yes ]
  • Treatment-Related Mortality After Transplant [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
    The return of disease after its apparent recovery/cessation.


Estimated Enrollment: 49
Study Start Date: December 2013
Estimated Study Completion Date: August 2017
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: 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
Other Name: Clolar
Drug: Etoposide
Days 1-5: Etoposide 100mg/m^2 IV over 2 hours
Other Names:
  • Eposin
  • Etopophos
  • Vepesid
  • VP-16
Drug: Cyclophosphamide
Days 1-5: Cyclophosphamide 300 mg/m^2 as a 30-60 minute infusion
Other Name: Cytoxan
Biological: allogeneic hematopoietic cell transplantation
Between Days 28 and 42: infused independent of this study
Other Name: allo-HCT
Experimental: 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.
Drug: 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
Other Name: Clolar
Drug: Etoposide
Days 1-5: Etoposide 100mg/m^2 IV over 2 hours
Other Names:
  • Eposin
  • Etopophos
  • Vepesid
  • VP-16
Drug: Cyclophosphamide
Days 1-5: Cyclophosphamide 300 mg/m^2 as a 30-60 minute infusion
Other Name: Cytoxan
Biological: allogeneic hematopoietic cell transplantation
Between Days 28 and 42: infused independent of this study
Other Name: allo-HCT

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.

  Eligibility

Ages Eligible for Study:   up to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01677949

Contacts
Contact: Michael J. Burke, M.D. 612-625-0032 burke283@umn.edu

Locations
United States, Minnesota
Masonic Cancer Center, University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Brenda Weigel, M.D.    612-626-5501    weige007@umn.edu   
Principal Investigator: Brenda Weigel, M.D.         
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Michael Burke, M.D. Masonic Cancer Center, University of Minnesota
  More Information

No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT01677949     History of Changes
Other Study ID Numbers: 2011LS158, HM2012-05
Study First Received: August 28, 2012
Last Updated: July 8, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasm, Residual
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplastic Processes
Pathologic Processes
Clofarabine
Cyclophosphamide
Etoposide
Etoposide phosphate
Alkylating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists

ClinicalTrials.gov processed this record on October 20, 2014