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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).


Phase 2
18 Years
N/A
Not Enrolling
Both
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

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Trial Information

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).


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.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Disease-free survival

Outcome Description:

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.

Outcome Time Frame:

6 months

Safety Issue:

No

Principal Investigator

Judith Karp

Investigator Role:

Principal Investigator

Investigator Affiliation:

Johns Hopkins University

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-03158

NCT ID:

NCT00045396

Start Date:

June 2002

Completion Date:

Related Keywords:

  • 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
  • Congenital Abnormalities
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia

Name

Location

Johns Hopkins UniversityBaltimore, Maryland  21205