Brief Title
Tipifarnib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
Official Title
Phase I Trial of R115777 (NSC 702818) in Relapsed, Refractory or High Risk Myeloid Leukemia
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
Detailed Description
PRIMARY OBJECTIVES:
I. To define the maximum tolerated dose (MTD) of R115777 (tipifarnib) in patients with
relapsed, refractory, or high risk myeloid leukemias treated according to this regimen.
II. To assess the toxicity and preliminary assessment of efficacy of R115777 in patients with
relapsed, refractory, or high risk myeloid leukemias.
OUTLINE: This is a dose-escalation, multicenter study.
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
complete response (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.
Cohorts of 3-6 patients receive escalating doses of tipifarnib until the MTD is determined.
The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience
dose-limiting toxicity.
Patients are followed every 6 months for survival.
PROJECTED ACCRUAL: A total of 20-30 patients will be accrued for this study.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
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
Condition
Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome
Intervention
tipifarnib
Study Arms / Comparison Groups
Treatment (tipifarnib)
Description: 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.
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
30
Start Date
October 2004
Primary Completion Date
May 2011
Eligibility Criteria
Inclusion Criteria:
- 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
- There must be no plans for the patient to receive concurrent hormonal, biologic, or
radiation therapy
- Patients eligible, at the time of starting the drug, for curative therapeutic
approaches (such as allogeneic transplant) are not eligible for the trial; however,
patients who achieve CR or PR as a result of R115777 may go on to allogeneic
transplant
- Patients must be informed of the investigational nature of this study and must sign
and give written informed consent in accordance with institutional and federal
guidelines
- Prior to the first patient registration, the notification of institutional review
board approval for this study must be provided to the Data Coordinating Center at City
of Hope
- Antacids are allowed but must not be taken concurrently with R115777; (there must be
at least 2 hours between antacid intake and R115777 dosing)
- Pregnant or lactating women are excluded from this trial; all patients of
child-bearing potential, both male and female, must be advised to practice adequate
contraception; premenopausal women must have a negative pregnancy test prior to entry
on this study
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Mark Kirschbaum, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00101296
Organization ID
NCI-2012-03078
Secondary IDs
PHI-47
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
Mark Kirschbaum, Principal Investigator, City of Hope Medical Center
Verification Date
January 2013