Leukemia
Conditions
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)
Brief 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.
Detailed description
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.
Interventions
DRUGclofarabine
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
DRUGtemsirolimus
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.
Sponsors
Gruppo Italiano Malattie EMatologiche dell'Adulto
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Complete Response Rate | At 2 years from study entry |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Serious Adverse Events Within 2 Years | At 2 years from study entry | — |
| Duration of Response | At 2 years from study entry | Participants who responded to treatment |
| Duration of Survival | At 2 years from study entry | — |
Countries
Italy
Participant flow
Recruitment details
Between April 2009 and June 2010, 60 patients were enrolled in the study at 14 different Italian institutions.
Participants by arm
| Arm | Count |
|---|---|
| Study Group Patients will receive one course of low-dose Clofarabine in combination with Temsirolimus (CloTor regimen) for remission induction. Those who achieve morphologic complete remission (CR) and morphologic complete remission with incomplete blood count recovery (CRi) will receive maintenance treatment with Temsirolimus monthly for 12 months, or until relapse. Those who achieve a partial remission (PR) will receive one additional course of CloTor and, if a CR/CRi is obtained, maintenance treatment with Temsirolimus as above. Patients not achieving CR or CRi after one or two induction courses will be discontinued from the study. | 53 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Unmet eligibility criteria | 6 |
Baseline characteristics
| Characteristic | Study Group |
|---|---|
| Age, Customized | 69 Years |
| Region of Enrollment Italy | 53 participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 15 / 53 |
Outcome results
Primary
Complete Response Rate
Time frame: At 2 years from study entry
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study Group | Complete Response Rate | 4 participants |
Secondary
Duration of Response
Participants who responded to treatment
Time frame: At 2 years from study entry
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | Duration of Response | 3.5 months | Standard Deviation 12 |
Secondary
Duration of Survival
Time frame: At 2 years from study entry
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Study Group | Duration of Survival | 10.9 months |
Secondary
Number of Serious Adverse Events Within 2 Years
Time frame: At 2 years from study entry
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study Group | Number of Serious Adverse Events Within 2 Years | 22 serious adverse events |