Brief Title
Flavopiridol, Cytarabine, and Mitoxantrone in Treating Patients With Relapsed or Refractory Acute Leukemia
Official Title
Phase I Study of a Pharmacologically Derived Hybrid Bolus-Infusion Schedule of Flavopiridol (NSC 649890, IND 46,211) Given in Timed Sequential Combination With Cytosine Arabinoside (Ara-C) and Mitoxantrone for Adults With Relapsed and Refractory Acute Leukemias
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.
Detailed Description
OBJECTIVES: I. Determine the toxicities of escalating doses of flavopiridol administered by "hybrid" bolus-infusion schedule and given in timed sequence with cytarabine and mitoxantrone hydrochloride in patients with refractory or relapsed acute leukemia. II. Determine the incidence of clinical response in patients treated with this regimen. OUTLINE: This is a dose-escalation study of flavopiridol. 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. Treatment repeats every 35-63 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 1 of 3 or 2 of 6 patients experience dose-limiting toxicity. Serum and bone marrow samples are collected at baseline, during, and after completion of treatment for future studies. Flavopiridol levels are measured at baseline and on days 1-3 for pharmacokinetics.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Maximum tolerated dose determined by dose-limiting toxicities graded according to NCI-CTC version 3.0
Condition
Adult Acute Megakaryoblastic Leukemia (M7)
Intervention
alvocidib
Study Arms / Comparison Groups
Arm I
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
35
Start Date
April 2007
Primary Completion Date
January 2011
Eligibility Criteria
Inclusion Criteria: - 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 - No active, uncontrolled infection - No other life-threatening illness - No mental deficits and/or psychiatric history that would preclude study compliance - No active graft-vs-host disease - Recovered from all prior therapies - At least 24 hours since prior hydroxyurea, steroids, imatinib mesylate, arsenic trioxide, interferon, or leukapheresis for blast count control - At least 4 weeks since prior stem cell transplantation (autologous or allogeneic) - At least 4 days since prior growth factors - At least 3 weeks since prior chemotherapy, except for non-aplasia producing treatments (e.g., low-dose cyclophosphamide, hydroxyurea, interferon, imatinib mesylate, mercaptopurine, thalidomide, azacitidine, or decitabine) - No prior flavopiridol - No other concurrent chemotherapy, radiotherapy, or immunotherapy - No acute promyelocytic leukemia (M3) - No hyperleukocytosis with > 50,000 blasts/mm^3
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Judith Karp, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00470197
Organization ID
NCI-2009-00243
Secondary IDs
NCI-2009-00243
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
Judith Karp, Principal Investigator, Johns Hopkins University
Verification Date
September 2013