Know Cancer

or
forgot password

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)


Phase 2
70 Years
N/A
Not Enrolling
Both
Leukemia

Thank you

Trial Information

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)


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Complete response

Outcome Time Frame:

6 months

Safety Issue:

No

Principal Investigator

Judith E. Karp, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

J07109 CDR0000584212

NCT ID:

NCT00602771

Start Date:

January 2008

Completion Date:

Related Keywords:

  • Leukemia
  • 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)
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid

Name

Location

University of Michigan Comprehensive Cancer CenterAnn Arbor, Michigan  48109-0752
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410
New York Weill Cornell Cancer Center at Cornell UniversityNew York, New York  10021
Blood and Marrow Transplant Group of GeorgiaAtlanta, Georgia  30342-1601