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Clofarabine With Cytarabine for Patients With Minimal Residual Disease Positive Leukemia

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ClinicalTrials.gov Identifier: NCT01158885
Recruitment Status : Terminated (Study terminated for lack of accrual.)
First Posted : July 8, 2010
Last Update Posted : October 26, 2012
Sponsor:
Collaborator:
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
Therapeutic Advances in Childhood Leukemia Consortium

Tracking Information
First Submitted Date  ICMJE June 30, 2010
First Posted Date  ICMJE July 8, 2010
Last Update Posted Date October 26, 2012
Study Start Date  ICMJE August 2010
Actual Primary Completion Date October 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 8, 2010)
Ability of clofarabine and cytarabine to eliminate minimal residual disease (MRD) in acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) patients whose bone marrows exhibit complete remission by morphology. [ Time Frame: Day 22-36 of course 1 and 2 ]
Patient's bone marrow will be evaluated for the amount of minimal residual disease (MRD) present after treatment on course 1 and 2.
Original Primary Outcome Measures  ICMJE
 (submitted: July 7, 2010)
Ability of clofarabine + cytarabine to eliminate minimal residual disease (MRD) in AML and ALL patients whose bone marrows exhibit complete remission by morphology. [ Time Frame: Day 22-36 of course 1 and 2 ]
Patient's bone marrow will be evaluated for the amount of MRD present after treatment on course 1 and 2.
Change History Complete list of historical versions of study NCT01158885 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 8, 2010)
  • To describe the toxicity profile with this treatment [ Time Frame: Day 1-36 of course 1 and 2 ]
    All toxicities and adverse events will be collected throughout the study.
  • To describe the toxicity profile during hematopoietic cell transplant (HCT) for patients who achieve remission and proceed to transplant. [ Time Frame: Every 3 months for life following completion or protocol therapy. ]
    After the patient completes therapy on this protocol, data will continue to be collected regarding whether the patient proceeded to HCT. Toxicity and adverse event information will be collected.
  • To determine the duration of complete remission after this treatment to minimize minimal residual disease. [ Time Frame: Every 3 months for life following completion or protocol therapy. ]
    If a patient eliminates all minimal residual disease (MRD) while being treated on this protocol. Data regarding the patient relapse will be collected to determine the length of remission.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 7, 2010)
  • To describe the toxicity profile with this treatment [ Time Frame: Day 1-36 of course 1 and 2 ]
    All toxicities and adverse events will be collected throughout the study.
  • To describe the toxicity profile during hematopoietic cell transplant (HCT) for patients who achieve remission and proceed to transplant. [ Time Frame: Every 3 months for life following completion or protocol therapy. ]
    After the patient completes therapy on this protocol, data will continue to be collected regarding whether the patient proceeded to HCT. Toxicity and adverse event information will be collected.
  • To determine the duration of complete remission after this treatment to minimize minimal residual disease. [ Time Frame: Every 3 months for life following completion or protocol therapy. ]
    If a patient eliminates all MRD while being treated on this protocol. Data regarding the patient relapse will be collected to determine the length of remission.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Clofarabine With Cytarabine for Patients With Minimal Residual Disease Positive Leukemia
Official Title  ICMJE Clofarabine With Cytarabine for MRD Positive Leukemia
Brief Summary This study will test the ability of clofarabine + cytarabine to eliminate minimal residual disease (MRD) in acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) patients whose bone marrows exhibit complete remission by morphology. The toxicity profile of this regimen will be evaluated in addition to toxicity experienced by patients who proceed to stem cell transplant. Overall length of remission will also be collected.
Detailed Description

Recent studies have demonstrated that even low levels of minimum residual disease (MRD) (>0.01% abnormal blasts) after aggressive re-induction therapy indicate a relatively poor outcome in relapsed acute lymphoblastic leukemia (ALL) patients, including those who proceed to allogeneic stem cell transplant (alloSCT). A similarly poor prognosis was seen in pediatric acute myelogenous leukemia patients with sub-morphologic disease prior to alloSCT. Studies to identify therapies that can eliminate persistent leukemia, have low toxicity profiles and can serve as a bridge to transplant are needed.

This study will test the ability of clofarabine + cytarabine to eliminate minimal residual disease (MRD) in acute myelogenous leukemia and acute lymphoblastic leukemia patients whose bone marrows exhibit complete remission by morphology. The toxicity profile of this regimen will be evaluated in addition to toxicity experienced by patients who proceed to stem cell transplant. Overall length of remission will also be collected.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Minimal Residual Disease
  • Leukemia, Lymphoblastic, Acute
  • Leukemia, Myelogenous, Acute
Intervention  ICMJE
  • Drug: Clofarabine
    20 mg/m2/day intravenously (IV) over 2 hours (given at hours 0 to 2) on days 1 through 5.
    Other Name: Clolar
  • Drug: Cytarabine
    1 gram/m2/day intravenously (IV) over 2 hours to be given 4 hours after the initiation of clofarabine on days 1 through 5.
    Other Name: AraC
  • Drug: Methotrexate

    Methotrexate to be given intrathecally (IT) to all acute lymphoblastic leukemia (ALL) patients on day 1 at the dose defined by age below:

    • 8 mg for patients age 1-1.99
    • 10 mg for patients age 2-2.99
    • 12 mg for patients 3-8.99 years of age
    • 15 mg for patients >9 years of age
    Other Name: MTX
  • Drug: Cytarabine

    Intrathecal (IT) cytarabine is optional for acute myelogenous leukemia (AML) patients.

    If intrathecal cytarabine is to be given, it must be given at least 72 hours but not more than 7 days prior to the initiation of intravenous cytarabine.

    Dose should be given according to age as defined below:

    • 30 mg for patients age 1-1.99
    • 50 mg for patients age 2-2.99
    • 70 mg for patients >3 years of age
    Other Name: AraC
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: October 24, 2012)
2
Original Estimated Enrollment  ICMJE
 (submitted: July 7, 2010)
36
Actual Study Completion Date  ICMJE October 2012
Actual Primary Completion Date October 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria: Patients must meet all of the following criteria to be eligible to participate in the study.

Patients must be ≥1 and ≤ 21 years of age when enrolled onto this study.

  • Diagnosis (Patient must have all of the following)

    • Patients must have a diagnosis of relapsed acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL)
    • Patient must have an M1 marrow based upon a recovered marrow with less than 5% blasts by conventional morphology
    • Patient must have minimal residual disease (MRD) detected by either multidimensional or conventional flow cytometry greater than 0.1% and less than 5% following any re-induction attempt
    • Patients must have a central nervous system (CNS) disease status of 1
  • Patient must have an absolute neutrophil count (ANC) >500/μL off cytokine support for at least 24 hours and platelets >50,000 K/μL without platelet transfusion in the past seven days
  • Karnofsky > 50% for patients > 10 years of age and Lansky > 50% for patients ≤ 10 years of age.
  • Patient must have adequate venous access.
  • Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
  • At least 21 days must have elapsed from prior chemotherapy, at least 7 days must have elapsed since receiving biological therapy.
  • It must be at least 90 days from any higher dose cytarabine therapy (>1 gm/ m2/day).
  • Patients must have a normal calculated creatinine clearance
  • Patient must have

    1. Conjugated (direct) serum bilirubin ≤ 1.5 x upper limit of normal (ULN) for age.
    2. Alanine transaminase (ALT) ≤ 2.5 × ULN for age.
    3. Alkaline phosphatase ≤ 2.5 × ULN for age.
    4. Serum amylase ≤ 1.5 ULN for age.
    5. Serum Lipase is ≤ ULN for age.
  • Patient must have a shortening fraction > 28% or an ejection fraction > 50%.
  • Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed prior to enrollment.
  • Female patients with infants must agree not to breastfeed their infants while on this study.
  • Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study.
  • Patient must agree to submission of blood and bone marrow for assessment of minimal residual disease (MRD).
  • All patients and/or their parents or legal guardians must sign a written informed consent.

Exclusion Criteria:Patients who meet any of the following criteria will be excluded from participating in the study.

  • Patients with previous hematopoietic stem cell transplant (HSCT) within previous six months.
  • Patients who have had prior treatment with clofarabine.
  • Patients with CNS2 or CNS 3 disease or bulky chloromatous disease.
  • Patients with Down Syndrome.
  • Patients with a previous history of veno-occlusive disease (VOD) or findings consistent with a diagnosis of VOD.
  • Patients with a systemic fungal, bacterial, viral, or other infection not controlled.
  • Use of investigational agents within 30 days of planned treatment on this protocol.
  • Patient is receiving or plans to receive concomitant chemotherapy, radiation therapy, immunotherapy or other anti-cancer therapy other than is specified in the protocol.
  • Pregnant or lactating patients.
  • Any significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.
  • Have had a diagnosis of another malignancy, unless the patient has been disease-free for at least 3 years following the completion of curative intent therapy with the following exceptions:

    1. Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intra-epithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed.
    2. Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01158885
Other Study ID Numbers  ICMJE T2009-002
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Therapeutic Advances in Childhood Leukemia Consortium
Study Sponsor  ICMJE Therapeutic Advances in Childhood Leukemia Consortium
Collaborators  ICMJE Genzyme, a Sanofi Company
Investigators  ICMJE
Study Chair: Blythe Thomson, MD Seattle Children's Hospital
PRS Account Therapeutic Advances in Childhood Leukemia Consortium
Verification Date October 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP