Brief Title
S0432 Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia
Official Title
Phase II Studies of Two Different Schedules and Two Different Doses of the Farnesyl Transferase Inhibitor R115777 (Tipifarnib, Zarnestra®, NSC-702818) for Previously Untreated Acute Myeloid Leukemia (AML) in Patients of Age 70 or Older
Brief Summary
This randomized phase II trial is studying 4 different tipifarnib regimens to compare how
well they work in treating older patients with acute myeloid leukemia. Tipifarnib may stop
the growth of cancer cells by blocking the enzymes necessary for their growth
Detailed Description
PRIMARY OBJECTIVES:
I. To test whether any or all of four different regimens of R115777 (tipifarnib) is
sufficiently effective therapy for previously untreated acute myeloid leukemia (AML) in
patients of age 70 or older to warrant Phase III investigation. Additionally, to allow
increased access for patients to an agent that appears promising in this patient population.
II. To estimate the frequency and severity of toxicities of these regimens in this group of
patients.
III. To investigate in a preliminary manner the relationship of cytogenetics with response to
R115777 (tipifarnib) and assess whether karyotype represents a potential prognostic factor
among older AML patients who are not candidates for chemotherapy and are treated with
R1157777.
IV. To collect specimens for future correlations (e.g. RAS and downstream targets) to be
identified at a later date.
OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 4 treatment
arms.
ARM I: Patients receive oral tipifarnib twice daily on days 1-21. ARM II: Patients receive
oral tipifarnib twice daily on days 1-7 and 15-21. ARM III: Patients receive tipifarnib as in
arm I, but at a lower dose. ARM IV: Patients receive tipifarnib as in arm II, but at a lower
dose.
In all arms, courses repeat every 28 days in the absence of unacceptable toxicity or disease
progression. Patients who achieve a complete remission (CR) receive up to 3 additional
courses beyond CR. Patients in CR who develop recurrent disease after the completion of
therapy are eligible to receive tipifarnib again.
Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually
for 3 years.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Total response rate, defined as the proportion of patients who achieve CR or PR
Condition
Adult Acute Megakaryoblastic Leukemia (M7)
Intervention
tipifarnib
Study Arms / Comparison Groups
Arm I
Description: Arm I: Patients receive oral tipifarnib twice daily on days 1-21. In all arms, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Patients who achieve a complete remission (CR) receive up to 3 additional courses beyond CR. Patients in CR who develop recurrent disease after the completion of therapy are eligible to receive tipifarnib again.
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
296
Start Date
September 2004
Primary Completion Date
June 2006
Eligibility Criteria
Inclusion Criteria:
- Patients must have a morphologically confirmed diagnosis of acute myeloid leukemia
(AML) with classification other than WHO Acute Promyelocytic Leukemia (FAB M3), based
on bone marrow aspiration and biopsy performed within 14 days prior to registration;
if a diagnostic biopsy has been performed within 28 days prior to registration, the
marrow blast percentage is >= 70%, and no potentially anti-leukemic therapy has been
given in the interim, then this bone marrow examination can be used for registration
purposes; Note: This protocol uses the WHO diagnostic criteria for AML, not the FAB
criteria; patients with WHO Acute Promyelocytic Leukemia (FAB M3) or blastic
transformation of chronic myelogenous leukemia are not eligible; patients must not be
candidates for or must have refused standard AML cytotoxic chemotherapy regimens
- Patients must not have received prior systemic chemotherapy for acute leukemia with
the exception of hydroxyurea; patients must have a WBC =< 30,000/cmm within 1 day
prior to registration; administration of hydroxyurea to control high WBC count prior
to, during and after registration is permitted; patients with a history of prior
myelodysplastic syndrome are eligible; however, prior treatment with AML induction
type chemotherapy or high dose chemotherapy with hematopoietic stem cell support is
not allowed; patients may have received hematopoietic growth factors, thalidomide,
arsenic trioxide, signal transduction inhibitors, azacitidine, and low dose cytarabine
for treatment of myelodysplastic syndrome; however, the dose of cytarabine must be <
100 mg/M2/day; other low intensity therapies for MDS will also be permitted and should
be discussed with the Study Coordinator; patients must be off prior therapy for MDS
(excluding growth factors) and all toxicities must have resolved; if indicated, a
single dose of intrathecal chemotherapy may also be given before or concurrent with
induction chemotherapy
- Patient must have a bilirubin =< 1.5 x Institutional Upper Limit of Normal (IULN),
unless the elevation is due primarily to elevated unconjugated hyperbilirubinemia
secondary to Gilbert's syndrome or hemolysis and not to liver dysfunction
- SGOT (AST) =< 2.5 x IULN, or SGPT (ALT) =< 2.5 x IULN, or both within 14 days prior to
registration
- Patients must have a serum creatinine =< 1.5 x IULN within 14 days prior to
registration
- Southwest Oncology Group patients must be registered on SWOG-9007, the cytogenetics
protocol; collection of pretreatment marrow specimens must be completed within 14 days
prior to registration; pretreatment specimens of bone marrow must be submitted to an
approved Southwest Oncology Group Cytogenetics Laboratory for cytogenetic analysis;
note that protocol SWOG-9007 also requires submission of remission and relapse
specimens
- ECOG and CALGB have similar cytogenetics studies; please check with your group to find
out about requirements for participation; CTSU sites will not be participating in
SWOG-9007 and will not be submitting specimens for this study
- All patients must have cytogenetics performed and - if not registered to SWOG-9007 - a
cytogenetics report submitted to the Cytogenetics Office at the Southwest Oncology
Group Data Operations Center
- Southwest Oncology Group patients must be offered participation in S9910, the leukemia
centralized reference laboratories and tissue repositories ancillary study; if consent
is given, collection of pretreatment blood and/or marrow specimens must be completed
within 14 days prior to registration; if the patient consents to participate in S9910,
pretreatment specimens of marrow and/or peripheral blood must be submitted to the
Southwest Oncology Group Myeloid Repository at the University of New Mexico for
cellular and molecular studies; S9910 also requests submission of remission and
relapse specimens
- ECOG and CALGB have similar reference laboratories and repository protocols; please
check with your group to find out about requirements for participation
- CTSU sites will not be participating in S9910 and will not be submitting specimens for
this study
- Patients of reproductive potential must have agreed to use an effective contraceptive
method
- Patients with a prior malignancy are eligible; however, the patient must have
completed all chemotherapy and radiotherapy at least 6 months prior to study
registration; there should be no plan to begin therapy for the prior malignancy at the
time of study registration; concurrent hormonal therapy is allowed
- Patients who are expected to require treatment with enzyme inducing antiepileptic
drugs (EIAED) are not eligible for this study
- If day 14 or 30 falls on a weekend or holiday, the limit may be extended to the next
working day; in calculating days of tests and measurements, the day a test or
measurement is done is considered Day 0; therefore, if a test is done on a Monday, the
Monday two weeks later would be considered Day 14; this allows for efficient patient
scheduling without exceeding the guidelines
- All 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
- At the time of patient registration, the treating institution's name and ID number
must be provided to the Data Operations Center in Seattle in order to ensure that the
current (within 365 days) date of institutional review board approval for this study
has been entered into the data base
Gender
All
Ages
70 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Harry Erba, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00093418
Organization ID
NCI-2012-03038
Secondary IDs
S0432
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
Harry Erba, Principal Investigator, Southwest Oncology Group
Verification Date
January 2013