Leukemia
Conditions
Keywords
adult acute myeloid leukemia in remission, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), 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)
Brief summary
RATIONALE: Giving chemotherapy before an autologous stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood and/or bone marrow and stored. More chemotherapy and radiation therapy is given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and radiation therapy. Giving aldesleukin after transplant may help keep cancer cells from coming back after transplant. PURPOSE: This phase II trial is studying the side effects and how well giving busulfan and etoposide together with total-body irradiation followed by autologous stem cell transplant and aldesleukin works in treating patients with acute myeloid leukemia in first remission.
Detailed description
OBJECTIVES: * To evaluate the efficacy and toxicity of a preparative regimen comprising busulfan, etoposide, and fractionated total-body irradiation followed by autologous stem cell transplantation and aldesleukin after treatment with consolidation therapy comprising high-dose cytarabine with or without idarubicin in patients with acute myeloid leukemia in first remission. * To estimate the long-term disease-free survival of patients treated with this regimen. * To further evaluate the effect of prognostic factors (e.g., cytogenetics, WBC at presentation, and number of courses of induction therapy required to achieve remission) on the outcome of autologous stem cell transplantation and targeted busulfan dose. OUTLINE: * Consolidation therapy: Patients who received prior consolidation therapy are evaluated to determine the need for additional consolidation therapy. Patients who have not received prior consolidation therapy receive high-dose cytarabine IV over 3 hours every 12 hours on days 1-4 and idarubicin\* IV over 5-10 minutes on days 1-3. NOTE: \*Patients with good risk cytogenetics t(8;21), inv(16), or t(16;16) or patients who received \> 200 mg/m² of anthracycline do not receive idarubicin. * Stem cell collection: All patients receive filgrastim (G-CSF) IV or subcutaneously (SC) twice daily beginning 7 days after completion of high-dose cytarabine and continuing until peripheral blood stem cell (PBSC) collection is completed. Patients who do not have an adequate number of PBSCs collected also undergo bone marrow collection. * Preparative regimen: Patients receive busulfan IV over 2 hours on days -13 and -11 to -7 and etoposide IV on day -2. Patients also undergo fractionated total-body irradiation on days -6 to -3 for a total of 8-10 fractions. * Autologous stem cell transplantation: Patients undergo autologous stem cell transplantation using PBSCs (with or without bone marrow) on day 0. Patients receive G-CSF IV or SC daily beginning on day 5 and continuing until blood counts recover. * Interleukin therapy: Within 100 days post-transplantation, patients receive aldesleukin IV continuously on days 1-4 and 9-18. After completion of study treatment, patients are followed periodically.
Interventions
BIOLOGICALaldesleukin
BIOLOGICALfilgrastim
DRUGbusulfan
DRUGcytarabine
DRUGetoposide
DRUGidarubicin
PROCEDUREautologous hematopoietic stem cell transplantation
PROCEDUREbone marrow transplantation
PROCEDUREperipheral blood stem cell transplantation
RADIATIONtotal-body irradiation
Sponsors
National Cancer Institute (NCI)
City of Hope Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Diagnosis of acute myeloid leukemia (AML) * FAB types M0-2 and M4-M7 * No M3 disease * In first complete hematological remission as confirmed by marrow aspiration and biopsy * No cytogenetic abnormality in the remission marrow * In complete remission for less than 6 months * Patients who have been in complete remission for more than 6 months may be eligible upon approval of the principal investigator * No prior myeloproliferative disorder (e.g., chronic myeloid leukemia, myelofibrosis, essential thrombocytosis, or polycythemia vera) * No prior myelodysplasia or secondary leukemia PATIENT CHARACTERISTICS: * FEV\_1 \> 60% * DLCO \> 50% * Cardiac ejection fraction ≥ 50% * Creatinine clearance \> 60 mL/min * No severe chronic medical or psychological illness that, in the judgement of the principal investigator, would jeopardize the ability of the patient to tolerate aggressive chemotherapy * No HIV positivity * Not pregnant * Negative pregnancy test PRIOR CONCURRENT THERAPY: * Prior consolidation therapy allowed * No concurrent use the following medications during aldesleukin therapy : * Corticosteroids (including blood product pre-meds) * Pentoxifylline * IV or intrathecal methotrexate * IV immunoglobulin * Other cytokines or growth factors
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-Free Survival at 2-Year Post-Transplant | Estimate at 2 years post treatment | Kaplan-Meier estimates at 2-years post-transplant, with 95% confidence intervals based on logit limit transformation of Greenwood's variance. Outcome is death or relapse, censor is alive in continual complete remission at the date of last clinical disease assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease-Free Survival at 2-Year Post-Transplant by Cytogenetic Risk | Kaplan-Meier estimate 2 years post treatment | Kaplan-Meier estimates at 2-years post-transplant, with 95% confidence intervals based on logit limit transformation of Greenwood's variance. Outcome is death or relapse, censor is alive in continual complete remission at the date of last clinical disease assessment. |
Participant flow
Recruitment details
60 patients went on-study. 52 went on to autologous transplant. Seven completed consolidation therapy without moving on to transplant. One was given an allogeneic transplant.
Participants by arm
| Arm | Count |
|---|---|
| HD ARA-C With Idarubicin, or Without Idarubicin if Previously Treated With an Anthracycline. HD ARA-C with Idarubicin Consolidation, Busulfan/FTBI/VP16/PSC/BMT
aldesleukin
filgrastim
busulfan
cytarabine
etoposide
idarubicin
autologous hematopoietic stem cell transplantation
peripheral blood stem cell transplantation
total-body irradiation | 52 |
| Total | 52 |
Baseline characteristics
| Characteristic | HD ARA-C With Idarubicin, or Without Idarubicin if Previously Treated With an Anthracycline. |
|---|---|
| Age, Categorical <=18 years | 2 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 50 Participants |
| Age, Continuous | 42.3 years |
| Race/Ethnicity, Customized Race/Ethnicity American Indian or Alaska Native, not of Hispanic Origin | 1 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Asian or Pacific Islander, not of Hispanic Origin | 3 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Black, not of Hispanic Origin | 2 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Hispanic | 6 Participants |
| Race/Ethnicity, Customized Race/Ethnicity White, not of Hispanic Origin | 40 Participants |
| Region of Enrollment United States | 52 participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 37 / 60 |
| other Total, other adverse events | 47 / 60 |
| serious Total, serious adverse events | 6 / 60 |
Outcome results
Primary
Disease-Free Survival at 2-Year Post-Transplant
Kaplan-Meier estimates at 2-years post-transplant, with 95% confidence intervals based on logit limit transformation of Greenwood's variance. Outcome is death or relapse, censor is alive in continual complete remission at the date of last clinical disease assessment.
Time frame: Estimate at 2 years post treatment
Population: Transplanted patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HD ARA-C Intermediate Cytogenetics | Disease-Free Survival at 2-Year Post-Transplant | 0.65 Proportion of pts alive in remission |
Secondary
Disease-Free Survival at 2-Year Post-Transplant by Cytogenetic Risk
Kaplan-Meier estimates at 2-years post-transplant, with 95% confidence intervals based on logit limit transformation of Greenwood's variance. Outcome is death or relapse, censor is alive in continual complete remission at the date of last clinical disease assessment.
Time frame: Kaplan-Meier estimate 2 years post treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HD ARA-C Intermediate Cytogenetics | Disease-Free Survival at 2-Year Post-Transplant by Cytogenetic Risk | 0.33 Proportion of pts alive in remission |
| Intermediate Risk Cytogenetics | Disease-Free Survival at 2-Year Post-Transplant by Cytogenetic Risk | 0.75 Proportion of pts alive in remission |
| Favorable Risk Cytogenetics | Disease-Free Survival at 2-Year Post-Transplant by Cytogenetic Risk | 0.75 Proportion of pts alive in remission |
| Unknown Risk: Rejected Cytogenetics Study | Disease-Free Survival at 2-Year Post-Transplant by Cytogenetic Risk | 0.73 Proportion of pts alive in remission |
Comparison: Null hypothesis: All four groups are drawn from the same distribution. Alternative hypothesis: At least one of the groups has measurably different survival from the others.p-value: 0.43Log Rank