Clofarabine and Temsirolimus in Treating Older Patients With Relapsed or Refractory Acute Myeloid Leukemia

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as clofarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Temsirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving clofarabine together with temsirolimus may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving clofarabine together with temsirolimus works in treating older patients with relapsed or refractory acute myeloid leukemia.

Detailed Description
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OBJECTIVES: Primary To determine the complete response rate in older patients with relapsed or refractory acute myeloid leukemia when treated with low-dose clofarabine and temsirolimus. Secondary To determine the tolerability and safety of this regimen. To determine the duration of response. To determine the duration of survival. OUTLINE: This is a multicenter study. Induction therapy: Patients receive clofarabine IV over 1 hour on days 1-5 and temsirolimus IV over 30 minutes on days 1, 8, and 15. Treatment continues for 1-2 courses in the absence of disease progression or unacceptable toxicity. Maintenance therapy: Patients achieving morphologic complete remission (CR) or CR with incomplete blood count recovery receive temsirolimus IV over 30 minutes on days 1 and 8 of each month. Treatment continues for 12 months in the absence of disease progression or unacceptable toxicity.

Official Title
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An Open Label Phase II Trial of Clofarabine and Temsirolimus in Older Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)

Conditions
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Leukemia

Intervention / Treatment
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* Drug: clofarabine
* Drug: temsirolimus


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Cytologically confirmed acute myeloid leukemia (AML) meeting the following criteria: At least 20% of blasts in the bone marrow AML in first relapse OR refractory to no more than one prior combination of intensive chemotherapy induction regimen No acute promyelocytic leukemia No blast transformation of chronic myeloid leukemia or other myeloproliferative disorders No active CNS leukemia PATIENT CHARACTERISTICS: WHO performance status 0-2 Life expectancy ≥ 4 weeks Serum total bilirubin ≤ 1.5 times upper limit of normal (ULN)* AST and ALT ≤ 2.5 times ULN* Serum creatinine ≤ 1.0 mg/dL* OR estimated glomerular filtration rate > 60 mL/min No active uncontrolled systemic infection No concurrent active malignancy No HIV positivity No severe concurrent medical condition or psychiatric disorder that would preclude study participation NOTE: *Unless due to organ leukemic involvement PRIOR CONCURRENT THERAPY: See Disease Characteristics More than 2 weeks since prior myelosuppressive chemotherapy At least 48 hours since prior hydroxyurea No prior clofarabine or temsirolimus No prior allogeneic stem cell transplantation No investigational drug within the past 30 days

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: clofarabine|Patients will receive one course of low-dose Clofarabine in combination with Temsirolimus (CloTor regimen) for remission induction. Induction therapy - Clofarabine 20 mg/m2/day, administered by iv infusion over 1 hour on days 1 through 5|
|Drug: temsirolimus|Those who achieve morphologic CR and morphologic CRi will receive maintenance treatment with Temsirolimus monthly for 12 months, or until relapse. Those who achieve a PR will receive one additional course of CloTor and, if a CR/CRi is obtained, maintenance treatment with Temsirolimus as above. Induction therapy: - Temsirolimus 25 mg (flat dose) administered iv over 30 minutes on days 1, 8 and 15. Maintenance therapy: - Temsirolimus 25 mg (flat dose) administered iv over 30 minutes on days 1 and 8 of each month for 12 months, or until relapse.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Rate |  | At 2 years from study entry | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Serious Adverse Events Within 2 Years |  | At 2 years from study entry | 
| Duration of Response | Participants who responded to treatment | At 2 years from study entry | 
| Duration of Survival |  | At 2 years from study entry | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult acute myeloid leukemia, adult acute basophilic leukemia, adult acute eosinophilic leukemia, adult erythroleukemia (M6a), adult pure erythroid leukemia (M6b), adult acute megakaryoblastic leukemia (M7), adult acute minimally differentiated myeloid leukemia (M0), adult acute monoblastic leukemia (M5a), adult acute monocytic leukemia (M5b), adult acute myeloblastic leukemia with maturation (M2), adult acute myeloblastic leukemia without maturation (M1), adult acute myelomonocytic leukemia (M4), adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute myeloid leukemia with inv(16)(p13;q22)