- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00045396
A Phase II Study Of The Farnesyltransferase Inhibitor ZANESTRA (R115777, NSC #702818, IND #58,359) In Complete Remission Following Induction And/Or Consolidation Chemotherapy In Adults With Poor-Risk Acute Myelogenous Leukemia (AML) And High-Risk Myelodysplasia (MDS)
A Phase II Study of the Farnesyltransferase Inhibitor ZARNESTRA (Tipifarnib, R115777, NSC #702818, IND #58,359) in Complete Remission Following Induction and/or Consolidation Chemotherapy in Adults With Poor-Risk Acute Myelogenous Leukemia (AML) and High-Risk Myelodysplasia (MDS).
Study Overview
Status
Conditions
- Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
- Adult Acute Myeloid Leukemia With Del(5q)
- 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 Myeloid Leukemia in Remission
- Secondary Myelodysplastic Syndromes
- Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
- de Novo Myelodysplastic Syndromes
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the duration of disease-free survival (DFS) and overall survival (OS) when ZARNESTRA is administered after intensive induction and consolidation chemotherapy to adults with poor risk acute myelogenous leukemia (AML) or high-risk myelodysplasia (MDS) in first complete remission (CR).
SECONDARY OBJECTIVES:
I. To determine the tolerability and toxicities of ZARNESTRA when administered in a chronic dosing schedule over a 48 week period to adults in first CR following intensive cytotoxic chemotherapies.
OUTLINE: This is a multicenter study.
Patients receive oral tipifarnib twice daily on days 1-14. Treatment repeats every 21 days for up to 16 courses in the absence of disease progression or unacceptable toxicity.
PROJECTED ACCRUAL: A total of 14-44 patients will be accrued for this study within 11-15 months.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
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:
- Pathological Confirmation of the Diagnosis of AML, MDS
- PMNs >= 1,000/ul
- Platelets >= 30,000/ul
- Hematocrit >= 27% and/or Hemoglobin >= 9 gm/dl unsupported
- ECOG Performance Status 0-2
- Patients must be able to give informed consent
- Female patients of childbearing age must have negative pregnancy test
- AST, ALT and Alkaline Phosphatase =<2.5 x normal
- Bilirubin =< 1.5 x normal
- Serum Creatinine =< 2.0 mg/dl or Creatinine Clearance >= 40 ml/min
- Left Ventricular Ejection Fraction >= 25%
Patients with poor-risk AML or high-risk MDS who have completed both induction and consolidation chemotherapy; poor risk AML is defined by one or more of the following characteristics:
- Antecedent Hematologic Disorder
- AML Arising from MDS
- Therapy-related AML
- Age >= 60 (in absence of favorable cytogenetics)
- Adverse Cytogenetics (i.e., -5/5q, -7/7q, +8, 20q-, 11q23 abnormalities, complex karyotype; other abnormalities may be considered at discression of study chair)
- Hyperleukocytosis at diagnosis (Blasts >= 30,000/mm^3 at diagnosis in absence of favorable cytogenetics)
High Risk MDS is defined by one or more of the following characteristics:
- RAEB and RAEB-t, with IPSS Score >= 1.5 (adverse cytogenetics, > 10% marrow blasts, cytopenias in at least 2 lineages): See Appendix E (Greenberg, et al. Blood 89:2079-2088,1997)36
- CMML with > 5% marrow blasts
- Therapy-related MDS
Exclusion Criteria:
- Any previous treatment with ZARNESTRA
- Ongoing participation in any Phase II or III clinical trial where DFS and OS are primary endpoints (unless patient is withdrawn from that trial)
- Acute promyelocytic (FAB M3) subtype
- Presence of (8;21) translocation or inversion 16 genotype as sole abnormality
- Eligible for curative allogeneic stem cell transplantation
- Known allergy to imidazole drugs (e.g., ketoconazole, miconazole)
- Presence of Residual AML (> 5% marrow blasts) or MDS, as Determined by Morphology, Flow Cytometry, and/or Cytogenetics
- Active, Uncontrolled Infection
- Disseminated Intravascular Coagulation
- Active CNS Leukemia
- Concomitant Chemotherapy, Radiation Therapy or Immunotherapy
- 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 (tipifarnib)
Patients receive oral tipifarnib twice daily on days 1-14.
Treatment repeats every 21 days for up to 16 courses in the absence of disease progression or unacceptable toxicity.
|
Given orally
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disease-free survival
Time Frame: 6 months
|
The trial is a success if greater than 45% of patients survive to 6 months.
Comparing this to the null hypothesis of 25% survival, we have 84% power to detect this difference using an exact 2-sided binominal test of proportions for alpha of 0.10.
This assumes no censoring occurs before 6 months.
|
6 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Tolerability and toxicities of ZARNESTRA when administrated in a chronic dosing schedule over a 48-week period to adults in first CR following intensive cytotoxic chemotherapy
Time Frame: Up to 48 weeks
|
Up to 48 weeks
|
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
Other Study ID Numbers
- NCI-2012-03158
- U01CA070095 (U.S. NIH Grant/Contract)
- U01CA069854 (U.S. NIH Grant/Contract)
- J0252
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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