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Clofarabine With Cytarabine for Patients With Minimal Residual Disease Positive Leukemia

Phase 2
Terminated
Conditions
Minimal Residual Disease
Leukemia, Lymphoblastic, Acute
Leukemia, Myelogenous, Acute
Interventions
Registration Number
NCT01158885
Lead Sponsor
Therapeutic Advances in Childhood Leukemia Consortium
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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
2
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Single ArmClofarabineA maximum of two courses of the following regimen will be administered. * Clofarabine: 20 mg/m2/day intravenously (IV) over 2 hours (given at hours 0 to 2) on days 1 through 5. * Cytarabine intravenous: 1 gram/m2/day intravenously (IV) over 2 hours to be given 4 hours after the initiation of clofarabine on days 1 through 5. * Methotrexate: to be given intrathecally (IT) to all acute lymphoblastic leukemia (ALL) patients on day 1 at the dose defined by age. * Intrathecal (IT) cytarabine: is optional for acute myelogenous leukemia (AML) patients.
Single ArmCytarabine intravenousA maximum of two courses of the following regimen will be administered. * Clofarabine: 20 mg/m2/day intravenously (IV) over 2 hours (given at hours 0 to 2) on days 1 through 5. * Cytarabine intravenous: 1 gram/m2/day intravenously (IV) over 2 hours to be given 4 hours after the initiation of clofarabine on days 1 through 5. * Methotrexate: to be given intrathecally (IT) to all acute lymphoblastic leukemia (ALL) patients on day 1 at the dose defined by age. * Intrathecal (IT) cytarabine: is optional for acute myelogenous leukemia (AML) patients.
Single ArmIntrathecal (IT) CytarabineA maximum of two courses of the following regimen will be administered. * Clofarabine: 20 mg/m2/day intravenously (IV) over 2 hours (given at hours 0 to 2) on days 1 through 5. * Cytarabine intravenous: 1 gram/m2/day intravenously (IV) over 2 hours to be given 4 hours after the initiation of clofarabine on days 1 through 5. * Methotrexate: to be given intrathecally (IT) to all acute lymphoblastic leukemia (ALL) patients on day 1 at the dose defined by age. * Intrathecal (IT) cytarabine: is optional for acute myelogenous leukemia (AML) patients.
Single ArmMethotrexateA maximum of two courses of the following regimen will be administered. * Clofarabine: 20 mg/m2/day intravenously (IV) over 2 hours (given at hours 0 to 2) on days 1 through 5. * Cytarabine intravenous: 1 gram/m2/day intravenously (IV) over 2 hours to be given 4 hours after the initiation of clofarabine on days 1 through 5. * Methotrexate: to be given intrathecally (IT) to all acute lymphoblastic leukemia (ALL) patients on day 1 at the dose defined by age. * Intrathecal (IT) cytarabine: is optional for acute myelogenous leukemia (AML) patients.
Primary Outcome Measures
NameTimeMethod
Minimal Residual Disease (MRD)Sample collected between Days 22-36 of courses 1 and 2

To be assessed in acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) patients whose bone marrows exhibit complete remission by morphology. Patient's bone marrow will be evaluated for the amount of minimal residual disease (MRD) present after treatment on courses 1 and 2.

Secondary Outcome Measures
NameTimeMethod
Occurrence of Toxicity During Hematopoietic Cell Transplant (HCT) for Patients Who Achieve Remission and Proceed to TransplantEvery 3 months for life following completion of 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.

Number of Patients With Dose-Limiting Toxicity (DLT)Beginning with the first dose of investigational product until day 56 of treatment course, an average of 1 year

Treatment related toxicities that preclude proceeding to HSCT by day 56 of the treatment course.

Trial Locations

Locations (2)

Carolina-Levine Children's Hospital

🇺🇸

Charlotte, North Carolina, United States

Seattle Children's Hospital

🇺🇸

Seattle, Washington, United States

Carolina-Levine Children's Hospital
🇺🇸Charlotte, North Carolina, United States

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