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

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 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

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