Tipifarnib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

NCT00101296 | Completed Phase 1

• 4 other identifiers: NCI-2012-03078PHI-47U01CA062505CDR0000404151
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. This phase I trial is studying the side effects and best dose of tipifarnib in treating patients with relapsed or refractory acute myeloid leukemia

Conditions

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (5)

• MTD defined as the highest dose level in which six patients have been evaluated for toxicity with no more than one patient experiencing dose limiting toxicity (DLT) assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0

  The toxicities observed at each dose level will be summarized in terms of type, severity, time of onset, duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.

  28 days

• Objective tumor response

  Will be summarized at each dose level, and the number and percent responding combined across dose levels.

  Up to 6.5 years

• Survival

  Will be summarized with Kaplan-Meier plots.

  From registration to time of death due to any cause, assessed up to 6.5 years

• Time to treatment failure

  Will be summarized with Kaplan-Meier plots.

  From registration to the first observation of disease progression, death due to any cause, or early discontinuation of treatment, assessed up to 6.5 years

• Duration of response

  Will be summarized with Kaplan-Meier plots.

  Up to 6.5 years

Study Arms (1)

Treatment (tipifarnib)

EXPERIMENTAL

Patients receive oral tipifarnib twice daily on days 1-7 and 15-21. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Patients achieving a CR receive 2 additional courses beyond CR. Patients experiencing relapse after previously achieving CR may receive additional tipifarnib at the current dose level for newly registered patients.

Drug: tipifarnib; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

tipifarnib DRUG

Given orally

Also known as: R115777, Zarnestra

Treatment (tipifarnib)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (tipifarnib)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (tipifarnib)

Eligibility Criteria

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

You may qualify if:

• Adult patients with acute myeloid leukemia (AML), excluding the M3 subtype (acute promyelocytic leukemia), that are not likely to respond to conventional therapy, including:
• Relapsed or refractory AML after one to three prior induction regimens (not counting consolidation therapies while in CR, such as autologous transplant),
• Newly diagnosed AML in patients up to age-70 with poor risk features (unfavorable cytogenetics or findings suggestive of prior myelodysplasia) not fit for standard induction therapy, and
• Newly diagnosed AML patients age 70 - 75 not fit for standard therapy (without history of prior myelodysplastic syndrome \[MDS\])
• Bone marrow and peripheral blood studies must be available for confirmation of diagnosis; cytogenetics, flow cytometry, and molecular studies (such as fms-related tyrosine kinase 3 \[Flt-3\] status) will be obtained as per standard practice
• Patients with active central nervous system (CNS) leukemia are NOT eligible
• Performance status of 60% or greater by the Karnofsky scale
• If induction chemotherapy has been attempted, a minimum of 4 weeks must have elapsed since the completion of prior chemotherapy in order to be eligible for this study; hydroxyurea for control of blasts is not counted as chemotherapy, and may be given up until 24 hours before starting R115777
• Patients may have had prior autologous transplant; they must be at least 100 days post transplant, and have had recovery of their counts with ANC \> 1000 and platelets greater than 100K at some point post transplant, and be without active CMV or fungal disease
• Patients may have received prior radiation therapy as part of a transplant conditioning regimen; radiotherapy must have been completed at least 100 days prior to starting on R115777
• There are no minimum hematological parameter requirements prior to the first two cycles of R115777, as patients with AML and MDS are understood to have low ANC and platelet counts when the disease is active; however, patients with WBC greater than 30,000 will receive hydroxyurea to reduce WBC to below 30,000 at which point they may begin treatment with R115777
• A pretreatment calculated creatinine clearance (absolute value) of \>= 60 ml/minute or serum creatinine of \< 1.5 x upper limit of normal is required
• Serum bilirubin =\< 2.0 mg/dl
• SGOT and SGPT =\< 2.5 times the institutional upper limits of normal
• Any condition causing inability to swallow pills given by mouth will render patients ineligible for the trial

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

City of Hope

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Leukemia, Erythroblastic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Congenital Abnormalities; Leukemia, Myelomonocytic, Acute

Interventions

tipifarnib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Mark Kirschbaum

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2005
• First Posted: January 10, 2005
• Study Start: October 1, 2004
• Primary Completion: May 1, 2011
• Last Updated: February 4, 2013

Record last verified: 2013-01

Locations

US (1)