Tipifarnib in Treating Patients With Acute Myeloid Leukemia in Remission

Phase 3

Completed

Conditions: Myelodysplastic Syndrome With Excess Blasts
Adult Acute Myeloid Leukemia in Remission
Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11
Adult Acute Myeloid Leukemia With Minimal Differentiation
Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A
Adult Erythroleukemia
Adult Pure Erythroid Leukemia
Alkylating Agent-Related Acute Myeloid Leukemia
Recurrent Adult Acute Myeloid Leukemia
Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1

Interventions: Drug: Tipifarnib
Procedure: Clinical Observation

Registration Number: NCT00093470

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This randomized phase III trial studies tipifarnib in treating patients with acute myeloid leukemia (AML) in remission. Tipifarnib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. It is not yet known whether tipifarnib is more effective than observation alone in preventing the recurrence of AML.

Detailed Description: PRIMARY OBJECTIVES:

I. To compare R115777 (tipifarnib) maintenance therapy to observation only with respect to disease-free survival (DFS) in patients with AML in second or subsequent complete remission or in complete response (CR) following primary induction failure.

SECONDARY OBJECTIVES:

I. To compare overall survival of patients in both arms. II. To evaluate the long-term safety and toxicity of extended administration of R115777 in AML patients in remission.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive tipifarnib orally (PO) twice daily (BID) on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients undergo observation only.

After completion of study treatment, patients are followed up for 5 years.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 144

Inclusion Criteria

Patients eligible to enter this study must fall into one of these categories:
- Patients in first remission following primary induction failure
- Patients must have received at least two chemotherapy induction regimens
- Patients in second or subsequent remission
- Patients > 60 years old in first remission
Patients must be in complete remission (CR) or morphologic remission (MR) by blood counts and bone marrow studies to enter the study
- Confirmatory bone marrow must be performed =< 2 weeks prior to randomization
Patients must have morphologic proof (from bone marrow aspirate, smears or touch preps of marrow biopsy) that they had AML of one of the following types prior to achievement of CR/MR
- Acute myeloblastic leukemia, minimal differentiation (French-American-British [FAB] M0)
- Acute myeloblastic leukemia without differentiation (FAB M1)
- Acute myeloblastic leukemia with maturation (FAB M2)
- Acute myelomonocytic leukemia (FAB M4)
- Acute monocytic leukemia (FAB M5)
- Acute erythroleukemia (FAB M6)
- Acute megakaryocytic leukemia (FAB M7)
- Refractory anemia with excess blasts in transformation (RAEB-T)
- AML by World Health Organization (WHO) criteria
- Acute myeloid leukemia with multilineage dysplasia
Patients with acute promyelocytic leukemia (FAB M3) are not eligible
Patients must be registered within 60 days of completion of therapy for the current remission; patients are eligible if they meet any of the criteria below:
- Within 60 days of remission (CR or MR) by peripheral blood counts following induction therapy or
- Within 60 days of discharge from the hospital following induction therapy or
- Within 60 days of discharge from the hospital following post-remission therapy or
- Within 60 days of recovery of blood counts following last dose of chemotherapy
All of the patients below are eligible for study entry:
- Patients who have received consolidation therapy
- Patients who have not received any consolidation or post remission therapy
- Patients who have had an autologous stem cell transplant
Patients who have received an allogeneic transplant (bone marrow transplant [BMT] or peripheral stem cell transplant [PSCT]) in their current remission are ineligible; patients who have had an allogeneic transplant in a previous remission and are currently in remission after subsequent relapse are eligible
Patients with a history of extramedullary disease are eligible if they are in complete remission at the time of study entry and no longer requiring therapy for their extramedullary disease
Patients must not be pregnant or breast-feeding; all females of childbearing potential must have a blood test or urine study < 2 weeks prior to randomization to rule out pregnancy
Women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception
Patients must not be known to have an allergy to imidazole drugs, such as clotrimazole ketoconazole, miconazole, econazole, or terconazole; this does not include fluconazole, voriconazole, or itraconazole
Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2
Patients must not have active cardiac or pulmonary disease; but patient will be eligible if disease is medically controlled
Patients must not have active renal disease; creatinine must be =< 1.5 x upper limit of normal
Patients must not have active hepatic disease; total or direct bilirubin must be < 2 mg/dl
Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) must be =< 2.5 times the upper limit of normal
Absolute neutrophil count (ANC) >= 1000/mm^3
Platelet count >= 50,000/mm^3
Patients must not be taking a hepatic enzyme-inducing anti-convulsant; a patient will not be eligible for the study if the patient is currently taking one of these agents and cannot be switched to a non-hepatic enzyme-inducing anti-convulsant

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A (tipifarnib)	Tipifarnib	Patients receive tipifarnib PO BID on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Arm B (clinical observation)	Clinical Observation	Patients undergo observation only.

Primary Outcome Measures

Name	Time	Method
Disease-free Survival	Assessed monthly for the first 6 months then every 3 months or as clinically indicated, up to 5 years.	Disease-free survival (DFS) is defined as the time from randomization to relapse or death without relapse.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	Assessed monthly for the first 6 months then every 3 months or as clinically indicated, up to 5 years.	Overall survival (OS) is defined as the time from randomization to death from any cause.

Trial Locations

Locations (340): University of Alabama at Birmingham Cancer Center
🇺🇸
Birmingham, Alabama, United States
Providence Alaska Medical Center
🇺🇸
Anchorage, Alaska, United States
Mayo Clinic in Arizona
🇺🇸
Scottsdale, Arizona, United States
Kaiser Permanente-San Diego Mission
🇺🇸
San Diego, California, United States
The Medical Center of Aurora
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Aurora, Colorado, United States
Boulder Community Hospital
🇺🇸
Boulder, Colorado, United States
Penrose-Saint Francis Healthcare
🇺🇸
Colorado Springs, Colorado, United States
Porter Adventist Hospital
🇺🇸
Denver, Colorado, United States
Presbyterian - Saint Lukes Medical Center - Health One
🇺🇸
Denver, Colorado, United States
SCL Health Saint Joseph Hospital
🇺🇸
Denver, Colorado, United States
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University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, United States