Comparing Three Different Combination Chemotherapy Regimens in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
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|ClinicalTrials.gov Identifier: NCT00634244|
Recruitment Status : Completed
First Posted : March 12, 2008
Results First Posted : July 7, 2015
Last Update Posted : July 7, 2015
|Condition or disease||Intervention/treatment||Phase|
|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 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 Myelomonocytic Leukemia (M4) Adult Erythroleukemia (M6a) Adult Pure Erythroid Leukemia (M6b) Recurrent Adult Acute Myeloid Leukemia||Drug: alvocidib Drug: mitoxantrone hydrochloride Drug: carboplatin Drug: cytarabine Drug: sirolimus Drug: etoposide Drug: topotecan hydrochloride||Phase 2|
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||92 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Randomized Trial of Carboplatin and Topotecan; Flavopiridol, Mitoxantrone and Cytosine Arabinoside; and Sirolimus, Mitoxantrone, Etoposide and Cytosine Arabinoside for the Treatment of Adults With Primary Refractory or Initial Relapse of Acute Myelogenous Leukemia (AML)|
|Study Start Date :||October 2008|
|Actual Primary Completion Date :||September 2014|
|Actual Study Completion Date :||October 2014|
Experimental: Arm A (carboplatin and topotecan hydrochloride)
Patients receive carboplatin and topotecan hydrochloride IV continuously over 24 hours on days 1-5.
Drug: topotecan hydrochloride
Experimental: Arm B (alvocidib, mitoxantrone, 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.
Drug: mitoxantrone hydrochloride
Experimental: Arm C (sirolimus, mitoxantrone, etoposide, 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)
Drug: mitoxantrone hydrochloride
- The Rate of Complete Remission (CR+CRi) [ Time Frame: 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).
- The Rate of Treatment Failure [ Time Frame: 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00634244
|United States, Alabama|
|University of Alabama at Birmingham|
|Birmingham, Alabama, United States, 35294|
|United States, Arizona|
|Mayo Clinic in Arizona|
|Scottsdale, Arizona, United States, 85259|
|United States, Florida|
|Mayo Clinic in Florida|
|Jacksonville, Florida, United States, 32224-9980|
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|United States, Iowa|
|Siouxland Hematology Oncology Associates|
|Sioux City, Iowa, United States, 51101|
|United States, Maryland|
|Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center|
|Baltimore, Maryland, United States, 21287|
|United States, Massachusetts|
|Tufts Medical Center|
|Boston, Massachusetts, United States, 02111|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|United States, Ohio|
|The Jewish Hospital|
|Cincinnati, Ohio, United States, 45236|
|United States, Pennsylvania|
|Geisinger Medical Center|
|Danville, Pennsylvania, United States, 17822-2001|
|Geisinger Medical Center-Cancer Center Hazleton|
|Hazleton, Pennsylvania, United States, 18201|
|Penn State Milton S Hershey Medical Center|
|Hershey, Pennsylvania, United States, 17033-0850|
|Lewistown, Pennsylvania, United States, 17044|
|Geisinger Medical Group|
|State College, Pennsylvania, United States, 16801|
|Mount Nittany Medical Center|
|State College, Pennsylvania, United States, 16803|
|Geisinger Wyoming Valley|
|Wilkes-Barre, Pennsylvania, United States, 18711|
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232|
|United States, Wisconsin|
|University of Wisconsin Hospital and Clinics|
|Madison, Wisconsin, United States, 53792|
|Froedtert and the Medical College of Wisconsin|
|Milwaukee, Wisconsin, United States, 53226|
|Rambam Medical Center|
|Haifa, Israel, 31096|
|Principal Investigator:||Mark Litzow||ECOG-ACRIN Cancer Research Group|