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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00045396
First received: September 6, 2002
Last updated: January 8, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
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
Drug: tipifarnib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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).

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Disease-free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 44
Study Start Date: June 2002
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: tipifarnib
Given orally
Other Names:
  • R115777
  • Zarnestra

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00045396

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: NCT00045396     History of Changes
Other Study ID Numbers: NCI-2012-03158, J0252, U01CA070095, U01CA069854
Study First Received: September 6, 2002
Last Updated: January 8, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Leukemia
Syndrome
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Disease
Pathologic Processes
Tipifarnib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014