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)

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

Conditions: Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; de Novo Myelodysplastic Syndromes; Adult Acute Myeloid Leukemia With Inv(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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With Del(5q)

Treatments: Drug: tipifarnib

Study type: Interventional

Funder types: NIH

Identifiers

NCT00045396

U01CA070095 (U.S. NIH Grant/Contract)

J0252

U01CA069854 (U.S. NIH Grant/Contract)

NCI-2012-03158

Details and patient eligibility

About

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

Full 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.

Enrollment: 44 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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44 participants in 1 patient group

Treatment (tipifarnib)

Experimental group

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.

Treatment:

Drug: tipifarnib