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

NCT ID: NCT00407966

Last Updated: 2015-08-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-10-31
• Study Completion Date: 2009-11-30

Brief Summary

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.

Detailed 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.

Conditions

Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; 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); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (alvocidib, cytarabine, mitoxantrone hydrochloride)

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.

Group Type: EXPERIMENTAL

alvocidib

Intervention Type: DRUG

Given IV

cytarabine

Intervention Type: DRUG

Given IV

mitoxantrone hydrochloride

Intervention Type: DRUG

Given IV

Interventions

alvocidib

Given IV

Intervention Type: DRUG

cytarabine

Given IV

Intervention Type: DRUG

mitoxantrone hydrochloride

Given IV

Intervention Type: DRUG

Other Intervention Names

FLAVO; flavopiridol; HMR 1275; L-868275; ARA-C; arabinofuranosylcytosine; arabinosylcytosine; Cytosar-U; cytosine arabinoside; CL 232315; DHAD; DHAQ; Novantrone

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Judith Karp

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University/Sidney Kimmel Cancer Center

Locations

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Countries

United States

References

Karp JE, Garrett-Mayer E, Estey EH, Rudek MA, Smith BD, Greer JM, Drye DM, Mackey K, Dorcy KS, Gore SD, Levis MJ, McDevitt MA, Carraway HE, Pratz KW, Gladstone DE, Showel MM, Othus M, Doyle LA, Wright JJ, Pagel JM. Randomized phase II study of two schedules of flavopiridol given as timed sequential therapy with cytosine arabinoside and mitoxantrone for adults with newly diagnosed, poor-risk acute myelogenous leukemia. Haematologica. 2012 Nov;97(11):1736-42. doi: 10.3324/haematol.2012.062539. Epub 2012 Jun 24.

Reference Type: DERIVED

PMID: 22733022 (View on PubMed)

Other Identifiers

NCI-2012-02986

Identifier Type: REGISTRY

Identifier Source: secondary_id

U01CA070095

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA006973

Identifier Type: NIH

Identifier Source: secondary_id

View Link

J0669

Identifier Type: OTHER

Identifier Source: secondary_id

7845

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2012-02986

Identifier Type: -

Identifier Source: org_study_id