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Clofarabine With Cytarabine for Patients With Minimal Residual Disease Positive Leukemia

This study has been terminated.
(Study terminated for lack of accrual.)
Sponsor:
Collaborator:
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
Therapeutic Advances in Childhood Leukemia Consortium
ClinicalTrials.gov Identifier:
NCT01158885
First received: June 30, 2010
Last updated: October 24, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Minimal Residual Disease
Leukemia, Lymphoblastic, Acute
Leukemia, Myelogenous, Acute
Drug: Clofarabine
Drug: Cytarabine
Drug: Methotrexate
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Clofarabine With Cytarabine for MRD Positive Leukemia

Resource links provided by NLM:


Further study details as provided by Therapeutic Advances in Childhood Leukemia Consortium:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Patient's bone marrow will be evaluated for the amount of minimal residual disease (MRD) present after treatment on course 1 and 2.


Secondary Outcome Measures:
  • To describe the toxicity profile with this treatment [ Time Frame: Day 1-36 of course 1 and 2 ] [ Designated as safety issue: Yes ]
    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. ] [ Designated as safety issue: Yes ]
    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. ] [ Designated as safety issue: No ]
    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.


Enrollment: 2
Study Start Date: August 2010
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    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
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.

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT01158885

  Show 25 Study Locations
Sponsors and Collaborators
Therapeutic Advances in Childhood Leukemia Consortium
Genzyme, a Sanofi Company
Investigators
Study Chair: Blythe Thomson, MD Seattle Children's Hospital
  More Information

No publications provided

Responsible Party: Therapeutic Advances in Childhood Leukemia Consortium
ClinicalTrials.gov Identifier: NCT01158885     History of Changes
Other Study ID Numbers: T2009-002
Study First Received: June 30, 2010
Last Updated: October 24, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Therapeutic Advances in Childhood Leukemia Consortium:
relapsed
relapse
refractory
Minimal Residual disease
MRD
MRD positive
MRD+
ALL
Acute lymphoblastic leukemia
AML
Acute myelogenous leukemia
Relapsed AML

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasm, Residual
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Leukemia, Lymphoid
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplastic Processes
Pathologic Processes
Clofarabine
Cytarabine
Methotrexate
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Antiviral Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents

ClinicalTrials.gov processed this record on November 25, 2014