Flavopiridol, Cytarabine, and Mitoxantrone in Treating Patients With Relapsed or Refractory Acute Leukemia

NCT00470197 | Completed Phase 1

• 6 other identifiers: NCI-2009-00243J06133CDR00005434437889U01CA070095U01CA062491
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

Brief Summary

Drugs used in chemotherapy, such as flavopiridol, 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 a new schedule of more than one drug (combination chemotherapy) may kill more cancer cells. This phase I trial is studying the side effects, best dose, and best schedule for flavopiridol when given together with cytarabine and mitoxantrone in treating patients with relapsed or refractory acute 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); Malignant Neoplasm; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose determined by dose-limiting toxicities graded according to NCI-CTC version 3.0

  Up to 63 days

Study Arms (1)

Arm I

EXPERIMENTAL

Patients receive flavopiridol IV over 30 minutes on days 1, 2, and 3. Patients receive cytarabine IV continuously over 72 hours beginning on day 6 and mitoxantrone hydrochloride IV over 60-120 minutes on day 9.

Drug: alvocidib; Drug: cytarabine; Drug: mitoxantrone hydrochloride; Other: pharmacological study

Interventions

alvocidib DRUG

Given IV

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

Arm I

cytarabine DRUG

Given IV

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

Arm I

mitoxantrone hydrochloride DRUG

Given IV

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

Arm I

pharmacological study OTHER

Correlative study

Also known as: pharmacological studies

Arm I

Eligibility Criteria

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

You may qualify if:

• Pathologically confirmed acute myeloid leukemia or acute lymphoblastic leukemia:
• Relapsed \>= 1 time OR refractory disease:
• Patients who fail primary induction therapy or who relapse after achieving complete remission are eligible if they have received =\< 3 prior courses of induction/reinduction therapy
• Relapsed \>= 1 time OR refractory disease
• Patients who fail primary induction therapy or who relapse after achieving complete remission are eligible if they have received =\< 3 prior courses of induction/reinduction therapy
• No active CNS leukemia
• ECOG performance status 0-2
• AST and ALT =\< 5 times upper limit normal (ULN)
• Alkaline phosphatase =\< 5 times ULN
• Bilirubin =\< 2.0 mg/dL
• Creatinine =\< 2.0 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• LVEF \>= 45% by MUGA or ECHO

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Johns Hopkins University

Baltimore, Maryland, 21287-8936, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• Karp JE, Smith BD, Resar LS, Greer JM, Blackford A, Zhao M, Moton-Nelson D, Alino K, Levis MJ, Gore SD, Joseph B, Carraway H, McDevitt MA, Bagain L, Mackey K, Briel J, Doyle LA, Wright JJ, Rudek MA. Phase 1 and pharmacokinetic study of bolus-infusion flavopiridol followed by cytosine arabinoside and mitoxantrone for acute leukemias. Blood. 2011 Mar 24;117(12):3302-10. doi: 10.1182/blood-2010-09-310862. Epub 2011 Jan 14.

  PMID: 21239698 DERIVED

MeSH Terms

Conditions

Leukemia, Megakaryoblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Congenital Abnormalities; Leukemia, Myelomonocytic, Acute; Leukemia, Erythroblastic, Acute; Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

alvocidib; Cytarabine; Mitoxantrone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds

Study Officials

• Judith Karp

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2007
• First Posted: May 7, 2007
• Study Start: April 1, 2007
• Primary Completion: January 1, 2011
• Last Updated: September 30, 2013

Record last verified: 2013-09

Locations

US (2)