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
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