Comparing Three Different Combination Chemotherapy Regimens in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

NCT00634244 | Completed Phase 2 Results

• 3 other identifiers: NCI-2009-00520E1906U10CA021115
• Study Type: interventional
• Target: 92
• Locations: 2 countries
• Sites: 20

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.

Conditions

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

Keywords

Acute Myelogenous Leukemia (AML), Carboplatin, Topotecan, Flavopiridol, Mitoxantrone, Cytosine Arabinoside, Sirolimus, Etoposide

Outcome Measures

Primary Outcomes (1)

• The Rate of Complete Remission (CR+CRi)

  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).

  Assessed every 3 months for the first 2 years and then every 6 months until relapse or death up to 3 years from registration.

Secondary Outcomes (1)

• 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.

Study Arms (3)

Arm A (carboplatin and topotecan hydrochloride)

EXPERIMENTAL

Patients receive carboplatin and topotecan hydrochloride IV continuously over 24 hours on days 1-5.

Drug: carboplatin; Drug: topotecan hydrochloride

Arm B (alvocidib, mitoxantrone, cytarabine)

EXPERIMENTAL

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: alvocidib; Drug: mitoxantrone hydrochloride; Drug: cytarabine

Arm C (sirolimus, mitoxantrone, etoposide, cytarabine)

EXPERIMENTAL

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; Drug: cytarabine; Drug: sirolimus; Drug: etoposide

Interventions

alvocidib DRUG

Given IV

Also known as: FLAVO, flavopiridol, HMR 1275, L-868275

Arm B (alvocidib, mitoxantrone, cytarabine)

mitoxantrone hydrochloride DRUG

Given IV

Also known as: CL 232315, DHAD, DHAQ

Arm B (alvocidib, mitoxantrone, cytarabine); Arm C (sirolimus, mitoxantrone, etoposide, cytarabine)

carboplatin DRUG

Given IV

Also known as: Carboplat, CBDCA, JM-8, Paraplat, Paraplatin

Arm A (carboplatin and topotecan hydrochloride)

cytarabine DRUG

Given IV

Also known as: ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside

Arm B (alvocidib, mitoxantrone, cytarabine); Arm C (sirolimus, mitoxantrone, etoposide, cytarabine)

sirolimus DRUG

Given PO

Also known as: AY 22989, Rapamune, rapamycin, SLM

Arm C (sirolimus, mitoxantrone, etoposide, cytarabine)

etoposide DRUG

Given IV

Also known as: EPEG, VP-16, VP-16-213

Arm C (sirolimus, mitoxantrone, etoposide, cytarabine)

topotecan hydrochloride DRUG

Given IV

Also known as: hycamptamine, Hycamtin, SKF S-104864-A, TOPO

Arm A (carboplatin and topotecan hydrochloride)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Induction Therapy:
• Patients must have morphologic proof (from bone marrow aspirate, smears or touch preps of marrow biopsy) of acute myelogenous leukemia (AML) with \>= 10% blasts within two weeks prior to induction randomization
• NOTE: Patients must be registered to E3903 (Ancillary Laboratory Protocol for Collecting Diagnostic Material on Patients Considered for Eastern Cooperative Oncology Group \[ECOG\]-American College of Radiology Imaging Network \[ACRIN\] Treatment Trials for Leukemia or Related Hematologic Disorders) and must undergo eligibility testing for the study by multiparameter flow cytometry
• All immunodiagnoses are eligible for E1906, except acute promyelocytic leukemia (APL) (proven by the presence of promyelocytic leukemia (PML)/retinoic acid receptor (RAR) alpha); cases of APL can become eligible if the patient is ineligible for an ECOG-ACRIN APL trial or if all-trans retinoic acid or arsenic trioxide is not planned as part of the treatment regimen
• Patients must qualify for one of the following:
• Relapse =\< 6 months after first CR, dated from documentation of CR to documentation of relapse
• Relapse between 6-12 months after first CR
• Refractory to conventional initial induction chemotherapy (=\< 2 courses) or to first reinduction (=\< 1 course)
• Normal cardiac ejection fraction by pretreatment multi gated acquisition scan (MUGA) or echocardiogram within 4 weeks prior to randomization (resting ejection fraction \>= 50% or \>= 5% increase with exercise), shortening fraction by echocardiogram \>= 24%, or to within the normal range of values for the institution
• Prior treatment to doses of any of the following:
• \< 300 mg/m\^2 of doxorubicin
• \< 300 mg/m\^2 of daunorubicin
• \< 100 mg/m\^2 of idarubicin
• \< 100 mg/m\^2 of mitoxantrone
• Serum creatinine =\< 2.0 mg/dL

You may not qualify if:

• Induction therapy:
• Patients who have relapsed \> 1 year after achieving first CR or are in \>= second relapse
• Patients who have had a prior allogeneic OR autologous stem cell transplant
• History of recent myocardial infarction (within three months), uncontrolled congestive heart failure, or uncontrolled cardiac arrhythmia
• Prior treatment with carboplatin, topotecan, flavopiridol, or sirolimus
• Pregnant or breast feeding. Women of childbearing potential and sexually active males should use an accepted and effective method of contraception
• Intercurrent organ damage or medical problems that would prohibit therapy; no active or unresolved infection
• Current evidence of invasive fungal infection; such evidence includes positive blood or deep tissue cultures or stains
• Have another (i.e., prior) tumor which is currently active and likely to interfere with the patient's treatment for AML or which is likely to compromise the patient's morbidity or mortality substantially
• Consolidation therapy:
• Intercurrent organ damage or medical problems that will jeopardize the outcome of therapy
• For arms B and C, patients have exceeded the following anthracycline doses or their equivalents:
• \< 300 mg/m\^2 of doxorubicin
• \< 300 mg/m\^2 of daunorubicin
• \< 100 mg/m\^2 of idarubicin

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (20)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Siouxland Hematology Oncology Associates

Sioux City, Iowa, 51101, United States

Location

Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

The Jewish Hospital

Cincinnati, Ohio, 45236, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822-2001, United States

Location

Geisinger Medical Center-Cancer Center Hazleton

Hazleton, Pennsylvania, 18201, United States

Location

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

Lewistown Hospital

Lewistown, Pennsylvania, 17044, United States

Location

Geisinger Medical Group

State College, Pennsylvania, 16801, United States

Location

Mount Nittany Medical Center

State College, Pennsylvania, 16803, United States

Location

Geisinger Wyoming Valley

Wilkes-Barre, Pennsylvania, 18711, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Rambam Medical Center

Haifa, 31096, Israel

Location

MeSH Terms

Conditions

Leukemia, Megakaryoblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Congenital Abnormalities; Leukemia, Myelomonocytic, Acute; Leukemia, Erythroblastic, Acute

Interventions

alvocidib; Mitoxantrone; Carboplatin; Cytarabine; Sirolimus; Etoposide; Topotecan; trioctyl phosphine oxide

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Myeloproliferative Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds; Coordination Complexes; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Macrolides; Lactones; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Glycosides; Carbohydrates; Camptothecin; Alkaloids

Results Point of Contact

• Title: Study Statistician
• Organization: ECOG Statistical Office

617-632-3012

Study Officials

• Mark Litzow

  ECOG-ACRIN Cancer Research Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2008
• First Posted: March 12, 2008
• Study Start: October 1, 2008
• Primary Completion: September 1, 2014
• Study Completion: October 1, 2014
• Last Updated: July 7, 2015
• Results First Posted: July 7, 2015

Record last verified: 2015-04

Locations

IL (1); US (19)