- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00016016
Flavopiridol, Cytarabine, and Mitoxantrone in Treating Patients With Acute Leukemia
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
Study Overview
Status
Conditions
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Maryland
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Baltimore, Maryland, United States, 21287-8936
- Johns Hopkins University
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
Given IV
Correlative studies
Given IV
Given IV
Correlative studies
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Dose-limiting toxicity (DLT) as assessed by NCI CTC version 2.0
Time Frame: Up to 35 days
|
Up to 35 days
|
Complete remission (CR)
Time Frame: Up to 6 years
|
Up to 6 years
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Disease Attributes
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Recurrence
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Leukemia, Lymphoid
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Peripheral Nervous System Agents
- Antiviral Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Growth Substances
- Growth Inhibitors
- Protein Kinase Inhibitors
- Cytarabine
- Mitoxantrone
- Alvocidib
Other Study ID Numbers
- NCI-2012-03153 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- U01CA070095 (U.S. NIH Grant/Contract)
- U01CA069854 (U.S. NIH Grant/Contract)
- 3170 (Other Identifier: CTEP)
- MSGCC-0052
- NCI-3170
- JHOC-J0254
- J0254 (Other Identifier: Johns Hopkins University)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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