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

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

Conditions: Adult Acute Megakaryoblastic Leukemia (M7); Adult Erythroleukemia (M6a); Adult Acute Basophilic Leukemia; Untreated Adult Acute Myeloid Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Pure Erythroid Leukemia (M6b); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Eosinophilic Leukemia; Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Myeloblastic Leukemia With Maturation (M2); Secondary Acute Myeloid Leukemia; Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monocytic Leukemia (M5b)

Treatments: Drug: cytarabine; Drug: mitoxantrone hydrochloride; Drug: alvocidib

Study type: Interventional

Funder types: NIH

Identifiers

NCT00407966

U01CA070095 (U.S. NIH Grant/Contract)

J0669 (Other Identifier)

P30CA006973 (U.S. NIH Grant/Contract)

NCI-2012-02986 (Registry Identifier)

7845 (Other Identifier)

Details and patient eligibility

About

This phase II trial is studying the side effects and how well giving alvocidib together with cytarabine and mitoxantrone works 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. Giving more than one drug (combination chemotherapy) may kill more cancer cells.

Full description

PRIMARY OBJECTIVES:

I. To determine the efficacy and toxicities of flavopiridol (alvocidib) followed by ara-C and mitoxantrone in adults with newly diagnosed acute myelogenous leukemia (AML) with poor-risk features.

II. To determine the disease free and overall survival of patients exhibiting a response to treatment with flavopiridol followed by ara-C and mitoxantrone.

OUTLINE:

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 1-2 hours on day 9. Beginning 35-63 days after completion of course 1, patients achieving complete or partial remission may receive a second course of treatment as above.

Patients age 50 and over with "core binding factor" acute myeloid leukemia (AML) (e.g., t[8;21], inv[16], or t[16;16]) achieving a complete remission after course 1 of treatment may receive 3-4 courses of consolidation therapy comprising high-dose cytarabine at the discretion of the investigator.

After completion of study treatment, patients are followed periodically.

Enrollment: 45 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adults with established, pathologically confirmed diagnoses of newly diagnosed, poor-risk Acute Myeloid Leukemia(AML) including de novo and secondary Acute Myeloid Leukemias but excluding newly diagnosed acute progranulocytic leukemia (APL, M3) will be considered eligible for study

• ECOG performance status 0-2

• Patient must be able to give informed consent

• Serum creatinine =< 2.0

• ALT, AST =< 5 x upper limit of normal

• Bilirubin =< 2.0 mg/dl

• Left ventricular ejection fraction >= 45%

• Newly diagnosed AML, subtypes M0,1,2,4-7 but excluding M3 (APL) with poor-risk features, including:

  • Age > 50 years, or age > 18 years with one or more of the following criteria:

    • Antecedent hematologic disorder including myelodysplasia (MDS)-related AML (MDS/AML) and prior myeloproliferative disorder (MPD)
    • Treatment-related AML
    • AML with trilineage dysplasia (AML-TLD)
    • 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)

Exclusion criteria

• Patients who have received hydroxyurea alone or have received non-cytotoxic therapies previously for MDS or MPD (e.g., thalidomide or lenalidomide, interferon, cytokines, low-dose 5-azacytidine, low-dose cytoxan) will be eligible for this trial
• Any previous treatment with flavopiridol
• Concomitant chemotherapy, radiation therapy, or immunotherapy
• Hyperleukocytosis with >= 50,000 blasts/uL; leukapheresis or hydroxyurea may be used immediately prior to study drug administration for cytoreduction; must be stopped 24 hours before first dose of Flavopiridol
• Acute Progranulocytic Leukemia (APL, M3)
• Active CNS leukemia
• Active, uncontrolled infection; patients with infection under active treatment and controlled with antibiotics are eligible
• Presence of other life-threatening illness
• Patients with mental deficits and/or psychiatric history that preclude them form giving informed consent or from following protocol
• Pregnant and nursing patients are excluded

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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45 participants in 1 patient group

Treatment (alvocidib, cytarabine, mitoxantrone hydrochloride)

Experimental group

Description:

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 1-2 hours on day 9. Beginning 35-63 days after completion of course 1, patients achieving complete or partial remission may receive a second course of treatment as above. Patients age 50 and over with "core binding factor" acute myeloid leukemia (AML) (e.g., t\[8;21\], inv\[16\], or t\[16;16\]) achieving a complete remission after course 1 of treatment may receive 3-4 courses of consolidation therapy comprising high-dose cytarabine at the discretion of the investigator.

Treatment:

Drug: mitoxantrone hydrochloride

Drug: cytarabine

Drug: alvocidib