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Tipifarnib and Etoposide in Treating Older Patients With Newly Diagnosed, Previously Untreated Acute Myeloid Leukemia

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ClinicalTrials.gov Identifier: NCT00602771
Recruitment Status : Completed
First Posted : January 28, 2008
Results First Posted : May 26, 2014
Last Update Posted : October 9, 2014
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Description
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Brief Summary:
This randomized phase II trial is studying the side effects and how well giving tipifarnib together with etoposide works in treating older patients with newly diagnosed, previously untreated acute myeloid leukemia. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving tipifarnib together with etoposide may kill more cancer cells.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome Adult Acute Megakaryoblastic Leukemia (M7) Adult Acute Minimally Differentiated Myeloid Leukemia (M0) Adult Acute Monoblastic Leukemia (M5a) 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) Secondary Acute Myeloid Leukemia Untreated Adult Acute Myeloid Leukemia Drug: tipifarnib Drug: etoposide Phase 2

Detailed Description:

OBJECTIVES:

I. To compare the efficacy and toxicity of two schedules of tipifarnib plus etoposide as induction therapy in older patients with newly diagnosed, previously untreated acute myeloid leukemia.

II. To study mechanisms of leukemia cell resistance to tipifarnib in combination with etoposide.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive 600 mg of oral tipifarnib twice daily on days 1-14 and 100 mg of oral etoposide once daily on days 1-3 and 8-10.

ARM II: Patients receive 400 mg of oral tipifarnib twice daily on days 1-14 and 200 mg of oral etoposide once daily on days 1-3 and 8-10. (closed to accrual as of November 2008)

Treatment in both arms repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 30 days and then every 90 days thereafter.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of Tipifarnib (R115777, ZARNESTRA, NSC #702818) in Combination With Oral Etoposide (VP-16) in Elderly Adults With Newly Diagnosed, Previously Untreated Acute Myelogenous Leukemia (AML)
Study Start Date : January 2008
Actual Primary Completion Date : October 2011
Actual Study Completion Date : October 2011

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm I
Patients receive 600 mg of oral tipifarnib twice daily on days 1-14 and 100 mg of oral etoposide once daily on days 1-3 and 8-10.
 Drug: tipifarnib
Given orally
Other Names:
  • R115777
  • Zarnestra

Drug: etoposide
Given orally
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Experimental: Arm II (closed to accrual as of November 2008)
Patients receive 400 mg of oral tipifarnib twice daily on days 1-14 and 200 mg of oral etoposide once daily on days 1-3 and 8-10.
 Drug: tipifarnib
Given orally
Other Names:
  • R115777
  • Zarnestra

Drug: etoposide
Given orally
Other Names:
  • EPEG
  • VP-16
  • VP-16-213


Outcome Measures
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Primary Outcome Measures :
  1. Complete Response [ Time Frame: 6 months ]
    Bone marrow showing less than 5% myeloblasts with normal maturation of all cell lines, an ANC of at least 1000/mcL and a platelet count of 100,000 mcL, absence of blast in peripheral blood, absence of identifiable leukemic cells in the bone marrow, clearance of disease-associated cytogenetic abnormalities, and clearance of any previously existing extramedullary disease. A CR must be confirmed 4 to 6 weeks after the initial documentation. If possible, at least one bone marrow biopsy should be performed to confirm the CR.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   70 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Criteria:

  • Pathologically confirmed newly diagnosed acute myeloid leukemia (AML)
  • Subtypes M0, M1, M2, M4-7 disease
  • No newly diagnosed acute promyelocytic leukemia (M3)
  • Any of the following diseases:
  • De novo disease
  • Secondary AML
  • Myelodysplasia (MDS)-related AML (MDS/AML)
  • Treatment-related AML
  • Previously untreated disease
  • Patients who have received prior hydroxyurea alone or non-cytotoxic therapies for MDS (e.g., thalidomide, interferon, cytokines, 5-azacytidine, or revlimid) will be eligible for this study
  • Must be considered ineligible for traditional antileukemia chemotherapy
  • No hyperleukocytosis with ≥ 30,000 blasts/uL or rapidly rising blast count with projected doubling time of =< 2 days
  • Patients may receive hydroxyurea to lower blast count to < 30,000 blasts/uL up to 24 hours before beginning tipifarnib and etoposide
  • No active CNS leukemia
  • No prior tipifarnib or etoposide
  • No concurrent radiotherapy, immunotherapy, or other chemotherapy
  • No concurrent enzyme-inducing anticonvulsants (e.g., phenytoin, fosphenytoin, phenobarbital, primidone, carbamazepine, or oxcarbazepine)
  • Patients may be changed to non-enzyme-inducing anticonvulsants and stabilized before starting study treatment

Inclusion Criteria:

  • ECOG performance status 0-2
  • Serum creatinine =< 2.0 mg/dL
  • SGOT and SGPT =< 3 times upper limit of normal
  • Bilirubin =< 2 mg/dL

Exclusion Criteria:

  • Active, uncontrolled infection
  • Patients with infection under active treatment and controlled with antimicrobials are eligible
  • Presence of other life-threatening illnesses
  • Patients with mental deficits and/or psychiatric history that preclude them from giving informed consent or from following protocol
  • Allergies to imidazoles (e.g., clotrimazole, ketoconazole, miconazole, or econazole)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00602771


Locations
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United States, Georgia
Blood and Marrow Transplant Group of Georgia
Atlanta, Georgia, United States, 30342
United States, Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States, 21287
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New York
Weill Medical College of Cornell University
New York, New York, United States, 10065
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Judith Karp Johns Hopkins University/Sidney Kimmel Cancer Center
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00602771    
Other Study ID Numbers: NCI-2009-00278
NCI-2009-00278 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000584212
J07109 ( Other Identifier: Johns Hopkins University/Sidney Kimmel Cancer Center )
8077 ( Other Identifier: CTEP )
N01CM62204 ( U.S. NIH Grant/Contract )
P30CA006973 ( U.S. NIH Grant/Contract )
U01CA070095 ( U.S. NIH Grant/Contract )
First Posted: January 28, 2008    Key Record Dates
Results First Posted: May 26, 2014
Last Update Posted: October 9, 2014
Last Verified: June 2014
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia, Monocytic, Acute
Leukemia, Myelomonocytic, Acute
Leukemia, Megakaryoblastic, Acute
Leukemia, Erythroblastic, Acute
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
 Hematologic Diseases
Myeloproliferative Disorders
Etoposide
Etoposide phosphate
Tipifarnib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action