Brief Title
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)
Official Title
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).
Brief Summary
Tipifarnib may stop the growth of cancer cells by blocking the enzymes necessary for their
growth. Phase II trial to study the effectiveness of tipifarnib in treating patients who have
acute myeloid leukemia or myelodysplastic syndrome in first complete remission
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 Phase
Phase 2
Study Type
Interventional
Primary Outcome
Disease-free survival
Secondary Outcome
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
Condition
Adult Acute Myeloid Leukemia in Remission
Intervention
tipifarnib
Study Arms / Comparison Groups
Treatment (tipifarnib)
Description: 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.
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
44
Start Date
June 2002
Primary Completion Date
October 2007
Eligibility Criteria
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
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
NCT00045396
Organization ID
NCI-2012-03158
Secondary IDs
J0252
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
Judith Karp, Principal Investigator, Johns Hopkins University
Verification Date
January 2013