A Study of Clofarabine and Cytarabine for Older Patients With Relapsed or Refractory Acute Myelogenous Leukemia (AML)(CLASSIC I)
Condition: Acute Myelogenous Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: clofarabine (IV formulation); placebo; cytarabine
Intervention description: clofarabine (IV formulation) infusion 40mg/m^2 / day up to 3 cycles; placebo (sodium Chloride) 1-hour IV infusion; cytarabine IV infusion 1g/m^2/day for up to 3 cycles
Intervention MeSH terms: Cytarabine; Clofarabine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 326.0
Sex: All
Minimum age: 55 Years
Healthy volunteers: No
Keywords: acute myelogenous leukemia; acute myeloid leukemia; relapsed AML; refractory AML; clofarabine; cytarabine; CLO341; clolar

Summary:

      Clofarabine (injection) is approved by the Food and Drug Administration (FDA) for the
      treatment of pediatric patients 1 to 21 years old with relapsed acute or refractory
      lymphoblastic leukemia (ALL) who have had at least 2 prior treatment regimens.

      There is no recommended standard treatment for relapsed or refractory acute myelogenous
      leukemia in older patients. Cytarabine is the most commonly used drug to treat these
      patients. This study will determine if there is benefit by combining clofarabine with
      cytarabine. Patients will be randomized to receive up to 3 cycles of treatment with either
      placebo in combination with cytarabine or clofarabine in combination with cytarabine.
      Randomization was stratified by remission status following the first induction regimen (no
      remission [i.e., CR1 = refractory] or remission <6 months vs CR1 = remission ≥6 months). CR1
      is defined as remission after first pre-study induction regimen. The safety and tolerability
      of clofarabine in combination with cytarabine and cytarabine alone will be monitored
      throughout the study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have a diagnosis of Acute Myelogenous Leukemia (AML) according to World Health
             Organization (WHO) classification

          -  Relapsed after receiving up to 2 prior induction regimens (i.e. first or second
             relapse)or are refractory to not more than one prior combination chemotherapy
             induction regimen

          -  Be ≥ 55 years of age

          -  Have an Eastern Cooperative Oncology Group (ECOG) score of 0-2

          -  Be able to comply with study procedures and follow-up examinations

          -  Be nonfertile or agree to use birth control during the study through the end of
             treatment visit and for at least 90 days after the last dose of study drug

          -  Have adequate liver and renal function as indicated by certain laboratory values

        Exclusion Criteria:

          -  Received previous treatment with clofarabine

          -  Received bolus, intermediate or high-dose cytarabine as induction therapy unless
             certain remission criteria are met

          -  Have received a hematopoietic stem cell transplant (HSCT) within the previous 3 months

          -  Have moderate or severe graft versus host disease (GVHD), whether acute or chronic

          -  Are receiving any other chemotherapy or investigational therapy. Patients must have
             been off prior AML therapy for at least 2-6 weeks prior to entering study.

          -  Have a psychiatric disorder that would interfere with consent, study participation, or
             follow-up

          -  Have an active, uncontrolled infection

          -  Have any other severe concurrent disease, or have a history of serious organ
             dysfunction or disease involving the heart, kidney, liver, or other organ system

          -  Have been diagnosed with another malignancy, unless disease-free for at least 5 years;
             patients with treated nonmelanoma skin cancer, in situ carcinoma, or cervical
             intraepithelial neoplasia, regardless of the disease-free duration, are eligible for
             this study if definitive treatment for the condition has been completed; patients with
             organ-confined prostate cancer with no evidence of recurrent or progressive disease
             are eligible if hormonal therapy has been initiated or the malignancy has been
             surgically removed.

          -  Have clinical evidence suggestive of central nervous system (CNS) involvement with
             leukemia unless lumbar puncture confirms absence of leukemic blasts in the
             cerebrospinal fluid(CSF)

          -  Known HIV positivity

          -  Are pregnant or lactating