Comparing Three Different Combination Chemotherapy Regimens in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
- Conditions
- Adult Acute Myeloblastic Leukemia Without Maturation (M1)Adult Acute Myeloid Leukemia With 11q23 (MLL) AbnormalitiesAdult Acute Myeloid Leukemia With Inv(16)(p13;q22)Adult Acute Myelomonocytic Leukemia (M4)Adult Acute Myeloblastic Leukemia With Maturation (M2)Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)Adult Acute Monoblastic Leukemia (M5a)Adult Acute Monocytic Leukemia (M5b)Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)Recurrent Adult Acute Myeloid Leukemia
- Interventions
- Registration Number
- NCT00634244
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This randomized phase II trial is comparing three different combination chemotherapy regimens to see how well they work in treating patients with relapsed or refractory acute myeloid leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating patients with relapsed or refractory acute myeloid leukemia.
- Detailed Description
PRIMARY OBJECTIVES:
I. To determine the complete remission (CR) + cytogenic complete remission (CRc) + morphologic complete remission with incomplete blood count recovery (CRi) rate of carboplatin and topotecan; flavopiridol, mitoxantrone and cytosine arabinoside and sirolimus, mitoxantrone, etoposide and cytosine arabinoside in adult patients with refractory or relapsed acute myeloid leukemia (AML).
NOTE: Since the CRc patients are required to be either CR or CRi, we only report the rate of CR+CRi in the results section.
II. To determine the rate of treatment failure of these regimens. III. To determine the incidence and severity of toxicities of these regimens. IV. To analyze the predictive value of blast cell properties that have been suggested to determine response. (Correlative laboratory studies) V. To determine whether pretreatment levels of B-cell chronic lymphocytic leukemia (CLL)/lymphoma 2 (Bcl-2) or, alternatively, whether a therapy-induced change in topoisomerase I levels correlates with response to this regimen. (Correlative laboratory studies) VI. To assess the impact of clonal evolution by comparing cytogenetic abnormalities at the time of relapse with those at initial diagnosis and correlating these abnormalities and changes with response to the treatment regimens in this protocol. (Cytogenetic and fluorescent in situ hybridization \[FISH\] studies) VII. Panel FISH studies for common AML rearrangements will be performed on relapse AML specimens to determine the presence of these recurrent AML abnormalities and to evaluate for subtle additional abnormalities consistent with clonal evolution in these relapse specimens. (Cytogenetic and FISH studies)
OUTLINE: Patients are randomized to 1 of 3 treatment arms.
INDUCTION THERAPY:
ARM A: Patients receive carboplatin and topotecan hydrochloride intravenously (IV) continuously over 24 hours on days 1-5.
ARM B: Patients receive alvocidib IV over 4.5 hours once daily (QD) on days 1-3, cytarabine IV continuously over 72 hours on days 6-8, and mitoxantrone hydrochloride IV over 1-2 hours on day 9.
ARM C: Patients receive sirolimus orally (PO) QD on days 2-9, mitoxantrone hydrochloride IV over 15 minutes QD, etoposide IV over 1 hour QD, and cytarabine IV over 3 hours QD on days 4-8 or 5-9. (Closed to accrual)
After completion of induction therapy, patients in all arms undergo bone marrow aspirate and biopsy. Patients with persistent leukemia (i.e., leukemic blasts \>= 10%) are removed from study and are offered alternative therapy at the discretion of the investigator. Patients who achieve CR proceed to consolidation therapy or receive alternative therapy at the discretion of the investigator.
CONSOLIDATION THERAPY: Beginning within 2-6 weeks after documentation of CR, patients may receive up to 2 additional courses of the same treatment they received during induction therapy. Courses repeat every 4-10 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed periodically for up to 3 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 92
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm C (sirolimus, mitoxantrone, etoposide, cytarabine) mitoxantrone hydrochloride Patients receive sirolimus PO QD on days 2-9, mitoxantrone hydrochloride IV over 15 minutes QD, etoposide IV over 1 hour QD, and cytarabine IV over 3 hours QD on days 4-8 or 5-9. (Closed to accrual) Arm A (carboplatin and topotecan hydrochloride) topotecan hydrochloride Patients receive carboplatin and topotecan hydrochloride IV continuously over 24 hours on days 1-5. Arm B (alvocidib, mitoxantrone, cytarabine) mitoxantrone hydrochloride Patients receive alvocidib IV over 4.5 hours QD on days 1-3, cytarabine IV continuously over 72 hours on days 6-8, and mitoxantrone hydrochloride IV over 1-2 hours on day 9. Arm A (carboplatin and topotecan hydrochloride) carboplatin Patients receive carboplatin and topotecan hydrochloride IV continuously over 24 hours on days 1-5. Arm B (alvocidib, mitoxantrone, cytarabine) cytarabine Patients receive alvocidib IV over 4.5 hours QD on days 1-3, cytarabine IV continuously over 72 hours on days 6-8, and mitoxantrone hydrochloride IV over 1-2 hours on day 9. Arm C (sirolimus, mitoxantrone, etoposide, cytarabine) etoposide Patients receive sirolimus PO QD on days 2-9, mitoxantrone hydrochloride IV over 15 minutes QD, etoposide IV over 1 hour QD, and cytarabine IV over 3 hours QD on days 4-8 or 5-9. (Closed to accrual) Arm C (sirolimus, mitoxantrone, etoposide, cytarabine) cytarabine Patients receive sirolimus PO QD on days 2-9, mitoxantrone hydrochloride IV over 15 minutes QD, etoposide IV over 1 hour QD, and cytarabine IV over 3 hours QD on days 4-8 or 5-9. (Closed to accrual) Arm C (sirolimus, mitoxantrone, etoposide, cytarabine) sirolimus Patients receive sirolimus PO QD on days 2-9, mitoxantrone hydrochloride IV over 15 minutes QD, etoposide IV over 1 hour QD, and cytarabine IV over 3 hours QD on days 4-8 or 5-9. (Closed to accrual) Arm B (alvocidib, mitoxantrone, cytarabine) alvocidib Patients receive alvocidib IV over 4.5 hours QD on days 1-3, cytarabine IV continuously over 72 hours on days 6-8, and mitoxantrone hydrochloride IV over 1-2 hours on day 9.
- Primary Outcome Measures
Name Time Method The Rate of Complete Remission (CR+CRi) Assessed every 3 months for the first 2 years and then every 6 months until relapse or death up to 3 years from registration. CR requires: 1. peripheral blood counts: neutrophil count ≥ 1.0 x 10\^9/L, platelet count ≥ 100 x 10\^9/L, reduced hemoglobin concentration or hematocrit has no bearing on remission status, and leukemic blasts must not be present in the peripheral blood. 2. bone marrow aspirate and biopsy: maturation of all cell lines must be present, ≤ 5% blasts, auer rods must not be detectable. 3. extramedullary leukemia, such as central nervous system (CNS) or soft tissue involvement, must not be present. CRi requires that all criteria for complete remission be satisfied except patients can have residual neutropenia (\<1 x 10\^9/L) or thrombocytopenia (\<100 x 10\^9/L).
- Secondary Outcome Measures
Name Time Method The Rate of Treatment Failure Assessed every 3 months for the first 2 years and then every 6 months until relapse or death up to 3 years from registration. The definition of treatment failure will include:
* ≥ 5% leukemic blasts at the time of pre-consolidation marrow
* Death during/following induction chemotherapy (pre-consolidation)
* Persisting marrow hypoplasia and pancytopenia for ≥ 2 months after chemotherapy
* CNS or extramedullary disease at the time of pre-consolidation
* Leukemia persistence after completion of induction treatment. Leukemia persistence is defined as greater than 10% residual blasts on marrow biopsy done 5-7 days after completion of induction chemotherapy
Trial Locations
- Locations (20)
Northwestern University
🇺🇸Chicago, Illinois, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Mayo Clinic in Florida
🇺🇸Jacksonville, Florida, United States
The Jewish Hospital
🇺🇸Cincinnati, Ohio, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Lewistown Hospital
🇺🇸Lewistown, Pennsylvania, United States
University of Wisconsin Hospital and Clinics
🇺🇸Madison, Wisconsin, United States
Rambam Medical Center
🇮🇱Haifa, Israel
Froedtert and the Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Mayo Clinic in Arizona
🇺🇸Scottsdale, Arizona, United States
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States
Siouxland Hematology Oncology Associates
🇺🇸Sioux City, Iowa, United States
Penn State Milton S Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Geisinger Medical Group
🇺🇸State College, Pennsylvania, United States
Mount Nittany Medical Center
🇺🇸State College, Pennsylvania, United States
Geisinger Medical Center-Cancer Center Hazleton
🇺🇸Hazleton, Pennsylvania, United States
Geisinger Wyoming Valley
🇺🇸Wilkes-Barre, Pennsylvania, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States