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

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00602771
First received: January 19, 2008
Last updated: January 25, 2012
Last verified: January 2012
History of Changes
  Purpose

RATIONALE: 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.

PURPOSE: 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.


Condition Intervention Phase
Leukemia
 Drug: etoposide
Drug: tipifarnib
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of Tipifarnib (R115777, ZARNESTRA, NSC #702818, IND #58,359) in Combination With Oral Etoposide (VP-16) in Elderly Adults With Newly Diagnosed, Previously Untreated Acute Myelogenous Leukemia (AML)

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Complete response [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Enrollment: 89
Study Start Date: January 2008
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: etoposide
Given orally once daily on days 1-3 and 8-10
Other Name: vp16
Drug: tipifarnib
Given orally twice daily on days 1-14
Other Name: Zarnestra
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: etoposide
Given orally once daily on days 1-3 and 8-10
Other Name: vp16
Drug: tipifarnib
Given orally twice daily on days 1-14
Other Name: Zarnestra

Detailed Description:

OBJECTIVES:

  • 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.
  • 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 (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.

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.

  Eligibility

Ages Eligible for Study:   70 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

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)

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00602771

Locations
United States, Georgia
Blood and Marrow Transplant Group of Georgia
Atlanta, Georgia, United States, 30342
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0942
United States, New York
New York Weill Cornell Cancer Center at Cornell University
New York, New York, United States, 10021
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
National Cancer Institute (NCI)
Investigators
Study Chair: Judith E. Karp, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

No publications provided by Sidney Kimmel Comprehensive Cancer Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00602771     History of Changes
Other Study ID Numbers: J07109 CDR0000584212, U01CA070095, P30CA006973, JHOC-J07109, JHOC-MD017
Study First Received: January 19, 2008
Last Updated: January 25, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
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 acute monocytic leukemia (M5b)
adult acute megakaryoblastic leukemia (M7)
secondary acute myeloid leukemia
adult acute myeloblastic leukemia without maturation (M1)
 adult acute myeloblastic leukemia with maturation (M2)
adult acute monoblastic leukemia (M5a)
adult erythroleukemia (M6a)
adult pure erythroid leukemia (M6b)
untreated adult acute myeloid leukemia
adult acute minimally differentiated myeloid leukemia (M0)
adult acute myeloid leukemia with inv(16)(p13;q22)

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Etoposide
 Etoposide phosphate
Tipifarnib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 18, 2013