Clofarabine and Temsirolimus in Treating Older Patients With Relapsed or Refractory Acute Myeloid Leukemia
Condition: Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: clofarabine; temsirolimus
Intervention description: 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; 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.
Intervention MeSH terms: Sirolimus; Temsirolimus; MTOR Inhibitors; Clofarabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 60.0
Sex: All
Minimum age: 60 Years
Healthy volunteers: No
Keywords: 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)

Summary:

      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.
    

Eligibility criteria:

        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