Alvocidib, Cytarabine, and Mitoxantrone in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

NCT00795002 | Completed Phase 2 Results

• 6 other identifiers: NCI-2009-00298CDR0000625222J08568237P30CA006973U01CA070095
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 2

Brief Summary

This randomized phase II trial is studying two different schedules of alvocidib to compare how well they work when given together with cytarabine and mitoxantrone in treating patients with newly diagnosed acute myeloid leukemia. Drugs used in chemotherapy, such as alvocidib, cytarabine, and mitoxantrone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It is not yet known which schedule of alvocidib is more effective when given together with cytarabine and mitoxantrone in treating patients with acute myeloid leukemia.

Conditions

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; 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 Del(5q); 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); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Complete Response

  Bone marrow showing less than 5% leukemic blasts with normal maturation of all cell lines, an ANC of at least 1000/uL and a platelet count of 100,000/uL, absence of blast in peripheral blood, absence of identifiable leukemic cells in the bone marrow, clearance of disease-associated cytogenetic abnormalities, and clearance of any previously existing extramedullary disease. Repeat marrow confirmation 4-6 weeks following the marrow documenting CR is not required due to the need for continued treatment in CR.

  1 year

Secondary Outcomes (2)

• Number of Participants Experiencing Death From Any Cause Within 60 Days of Starting FLAM

  60 days

• Disease-free Survival

  up to 2 years

Study Arms (2)

Arm I

EXPERIMENTAL

Patients receive alvocidib IV over 1 hour on days 1-3, cytarabine IV continuously over 72 hours on days 6-8, and mitoxantrone hydrochloride IV over 60-120 minutes on day 9.

Drug: alvocidib; Drug: mitoxantrone hydrochloride; Drug: cytarabine; Other: pharmacological study; Other: laboratory biomarker analysis

Arm II

EXPERIMENTAL

Patients receive alvocidib IV over 30 minutes followed by alvocidib IV over 4 hours on days 1-3. Patients also receive cytarabine and mitoxantrone hydrochloride as in arm I.

Drug: alvocidib; Drug: mitoxantrone hydrochloride; Drug: cytarabine; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

alvocidib DRUG

Given IV

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

Arm I; Arm II

mitoxantrone hydrochloride DRUG

Given IV

Also known as: CL 232315, DHAD, DHAQ, Novantrone

Arm I; Arm II

cytarabine DRUG

Given IV

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

Arm I; Arm II

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Arm I; Arm II

laboratory biomarker analysis OTHER

Correlative studies

Arm I; Arm II

Eligibility Criteria

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

You may qualify if:

• Pathologically confirmed newly diagnosed acute myeloid leukemia (AML) meeting the following criteria:
• Subtypes M0, M1, M2, M4-7
• No acute promyelocytic leukemia (M3)
• At least 50 years of age OR \>= 18 years of age with \>= 1 of the following poor-risk disease features:
• Antecedent hematologic disorder, including myelodysplastic syndromes (MDS)-related AML or prior myeloproliferative disorder (MPD)
• Treatment-related AML, AML with trilineage dysplasia
• Myeloid sarcoma, myeloid proliferations related to Down Syndrome, or blastic plasmacytoid dendritic cell neoplasm
• AML with trilineage dysplasia
• AML with adverse cytogenetics (defined as -5/-5q; -7/-7q; abnormal 3q, 9q, 11q, 20q, 21q, or 17p; t\[6;9\]; t\[9;22\]; trisomy 8; trisomy 13, complex karyotypes \[\>= 3 unrelated abnormalities\]),
• No hyperleukocytosis with \>= 50,000 blasts/uL (leukapheresis or hydroxyurea allowed for cytoreduction immediately prior to the first dose of alvocidib)
• No active CNS leukemia
• ECOG performance status 0-2
• Serum creatinine =\< 2.0 mg/dL
• ALT/AST =\< 5 times upper limit of normal
• Bilirubin =\< 2.0 mg/dL

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

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

Interventions

alvocidib; Mitoxantrone; Cytarabine

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; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Judith Karp, MD
• Organization: The Sidney Kimmel Comprehensive Cancer Center

jkarp2@jhmi.edu

410-502-7726

Study Officials

• Judith Karp

  Johns Hopkins University/Sidney Kimmel Cancer Center

  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: November 20, 2008
• First Posted: November 21, 2008
• Study Start: November 1, 2008
• Primary Completion: November 1, 2010
• Study Completion: September 1, 2012
• Last Updated: August 7, 2018
• Results First Posted: December 5, 2013

Record last verified: 2018-08

Locations

US (2)