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)

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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