Flavopiridol, Cytarabine, and Mitoxantrone in Treating Patients With Acute Leukemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00016016
First received: May 6, 2001
Last updated: October 7, 2013
Last verified: October 2013
  Purpose

Phase II trial to study the effectiveness of combining flavopiridol and cytarabine with mitoxantrone in treating patients who have acute leukemia. Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.


Condition Intervention Phase
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Acute Myeloid Leukemia
Secondary Acute Myeloid Leukemia
Untreated Adult Acute Lymphoblastic Leukemia
Untreated Adult Acute Myeloid Leukemia
Drug: cytarabine
Drug: mitoxantrone hydrochloride
Drug: alvocidib
Other: pharmacological study
Other: laboratory procedure
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Flavopiridol (NSC 649890, IND 46,211) in Timed Sequential Combination With Cytosine Arabinoside (Ara-C) and Mitoxantrone for Adults With Poor-Risk Acute Leukemias

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Dose-limiting toxicity (DLT) as assessed by NCI CTC version 2.0 [ Time Frame: Up to 35 days ] [ Designated as safety issue: Yes ]
  • Complete remission (CR) [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 53
Study Start Date: February 2001
Primary Completion Date: November 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (flavopiridol, cytarabine, mitoxantrone)
Patients receive flavopiridol IV over 1 hour on days 1-3 and cytarabine IV continuously on days 6-9 followed by mitoxantrone IV over 30-150 minutes on day 9. Patients achieving a partial or complete response after the first course of therapy may receive an additional course of therapy beginning 35 ± 7 days after blood count recovery.
Drug: cytarabine
Given IV
Drug: mitoxantrone hydrochloride
Given IV
Drug: alvocidib
Given IV
Other: pharmacological study
Correlative studies
Other: laboratory procedure
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the toxicities of escalating doses of flavopiridol administered in a timed sequence with ara-C and mitoxantrone in adults with refractory or relapsed acute leukemias or high-risk myelodysplasias (MDS).

II. To determine if flavopiridol administered in a timed sequence with ara-C and Mitoxantrone will induce clinical responses in adults with refractory or relapsed acute leukemias or MDS.

III. To determine if flavopiridol is directly cytotoxic to leukemic blasts in vivo.

IV. To determine if flavopiridol can recruit and synchronize residual leukemic blasts to proliferate in vivo.

OUTLINE: This is a dose-escalation study of flavopiridol. (Phase I closed to accrual effective10/24/2003).

Patients receive flavopiridol IV over 1 hour on days 1-3 and cytarabine IV continuously on days 6-9 followed by mitoxantrone IV over 30-150 minutes on day 9. Patients achieving a partial or complete response after the first course of therapy may receive an additional course of therapy beginning 35 ± 7 days after blood count recovery.

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 at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. (Phase I closed to accrual effective 10/24/2003). Once the MTD is reached, additional patients are accrued to receive flavopiridol at the recommended phase II dose.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Established diagnoses of poor-risk hematologic malignancies will be considered eligible for this Phase I/II study
  • Pathological confirmation of the diagnosis of AML or ALL
  • ECOG performance status 0,1,2
  • Patients must be able to give informed consent
  • Female patients of childbearing age must have negative pregnancy test
  • AST and ALT =< 2.5 x normal
  • Alkaline phosphatase =< 2.5 x normal
  • Bilirubin =< 1.5 x normal
  • Serum creatinine =< 2.0 mg/dl
  • Left ventricular ejection fraction must >= 45% by MUGA or Echocardiogram
  • Acute Myelogenous Leukemia (AML)

    • AML arising from MDS
    • Secondary AML
    • Relapsed or refractory AML, including primary induction failure
  • Acute Lymphoblastic Leukemia (ALL)

    • Relapsed or refractory ALL, including primary induction failure
    • Patients who fail primary induction therapy or who relapse after achieving complete remission (CR) are eligible if they have undergone no more than 3 prior courses of induction/reinduction
  • There should be an interval of at least 4 weeks from any previous intensive chemotherapy before beginning flavopiridol, with the exceptions non-aplasia producing treatments (i.e. hydroxyurea, interferon, imatinib, 6MP, thalidomide); patients should have recovered completely from any treatment-related toxicities; patients may have received hematopoietic growth factors previously, but must be off all growth factors (including EPO, G-CSF, GM-CSF, IL-3, IL-11) for at least 4 days prior to beginning flavopiridol
  • Patients who have undergone stem cell transplantation (SCT), autologous or allogeneic, are eligible provided that they are >= 4 weeks from stem cell infusion, have no active GVHD, and meet other eligibility criteria

Exclusion Criteria:

  • Hyperleukocytosis with >= 50,000 leukemic blasts/mm^3
  • Active, uncontrolled infection
  • Disseminated intravascular coagulation
  • Active CNS leukemia
  • Concomitant chemotherapy, radiation therapy or immunotherapy
  • Intrinsic impaired cardiac function (MI within the preceding 3 months or history of severe coronary artery disease, cardiomyopathy, CHF > Class II)
  • History of congestive heart disease, or arrhythmia without regard to time, severity or resolution
  • Women who are pregnant or lactating will not be eligible for this trial, as the investigational agent may be harmful to the developing fetus or nursing infant
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00016016

Locations
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287-8936
Sponsors and Collaborators
Investigators
Principal Investigator: Judith Karp Johns Hopkins University
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00016016     History of Changes
Other Study ID Numbers: NCI-2012-03153, NCI-2012-03153, MSGCC-0052, NCI-3170, JHOC-J0254, J0254, 3170, U01CA070095, U01CA069854
Study First Received: May 6, 2001
Last Updated: October 7, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cytarabine
Flavopiridol
Mitoxantrone
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Growth Inhibitors

ClinicalTrials.gov processed this record on July 22, 2014