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)

NCT00045396 | Completed Phase 2

• 4 other identifiers: NCI-2012-03158J0252U01CA070095U01CA069854
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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

Conditions

Adult Acute Myeloid Leukemia in Remission; 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(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); de Novo Myelodysplastic Syndromes; Secondary Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (1)

• Disease-free survival

  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 Outcomes (1)

• 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

  Up to 48 weeks

Study Arms (1)

Treatment (tipifarnib)

EXPERIMENTAL

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.

Drug: tipifarnib

Interventions

tipifarnib DRUG

Given orally

Also known as: R115777, Zarnestra

Treatment (tipifarnib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21287-8936, United States

Location

MeSH Terms

Conditions

Congenital Abnormalities

Interventions

tipifarnib

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Judith Karp

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2002
• First Posted: January 27, 2003
• Study Start: June 1, 2002
• Primary Completion: October 1, 2007
• Last Updated: January 9, 2013

Record last verified: 2013-01

Locations

US (1)