A Phase 3 interventional study of Clinical Observation and Tipifarnib in Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, Adult Acute Megakaryoblastic Leukemia and Adult Acute Monocytic Leukemia, sponsored by National Cancer Institute (NCI). Completed at 341 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-14.
Sponsored by National Cancer Institute (NCI) · Phase 3, Interventional, and Treatment
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.
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.
172 studies on the registry are indexed under Leukemia, Megakaryoblastic, Acute; none are open to participants now.
This study's enrollment of 144 is above the median of 45 across 137 interventional studies indexed under Leukemia, Megakaryoblastic, Acute.
Browse Leukemia, Megakaryoblastic, Acute studies →National Cancer Institute (NCI) is the lead sponsor of 3,556 studies on the registry; 336 are open to participants now.
Of its 411 completed or terminated interventional studies of FDA-regulated products, 373 (91%) have results posted.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria:
Patients eligible to enter this study must fall into one of these categories:
Patients must be in complete remission (CR) or morphologic remission (MR) by blood counts and bone marrow studies to enter the study
Patients must have morphologic proof (from bone marrow aspirate, smears or touch preps of marrow ) that they had AML of one of the following types prior to achievement of CR/MR
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:
All of the patients below are eligible for study entry:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Allogeneic and autologous transplant
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients receive tipifarnib PO BID on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Tipifarnib
Patients undergo observation only.
Procedure: Clinical Observation
Undergo observation
Also known as: observation
Given PO
Also known as: R115777, Zarnestra
Disease-free Survival
Disease-free survival (DFS) is defined as the time from randomization to relapse or death without relapse.
Time frame: Assessed monthly for the first 6 months then every 3 months or as clinically indicated, up to 5 years.
Overall Survival
Overall survival (OS) is defined as the time from randomization to death from any cause.
Time frame: Assessed monthly for the first 6 months then every 3 months or as clinically indicated, up to 5 years.
This study was activated on August 18, 2004, suspended between August 8, 2007 and February 6, 2008 for toxicity and safety evaluation, and closed on December 7, 2009 with a total of 144 patients accrued.
| Milestone | Arm A (Tipifarnib) | Arm B (Clinical Observation) |
|---|---|---|
| Started | 73 | 71 |
| Treated | 72 | 71 |
| Patients with toxicity assessment | 72 | 69 |
| Completed | 0 | 71 |
| Not completed | 73 | 0 |
| Withdrew: Disease progression | 39 | 0 |
| Withdrew: Adverse event | 15 | 0 |
| Withdrew: Death | 2 | 0 |
| Withdrew: Withdrawal by subject | 8 | 0 |
| Withdrew: Alternative therapy | 2 | 0 |
| Withdrew: Other complicating disease | 3 | 0 |
| Withdrew: Physician decision | 2 | 0 |
| Withdrew: Never started treatment | 1 | 0 |
| Withdrew: Anc < 1000 on day 1 of cycle 1 | 1 | 0 |
Disease-free survival (DFS) is defined as the time from randomization to relapse or death without relapse.
| months | Arm A (Tipifarnib) | Arm B (Clinical Observation) |
|---|---|---|
| Disease-free Survival | 8.87 (5.85 to 13.34) | 5.26 (3.88 to 7.56) |
Overall survival (OS) is defined as the time from randomization to death from any cause.
| months | Arm A (Tipifarnib) | Arm B (Clinical Observation) |
|---|---|---|
| Overall Survival | 16.36 (12.26 to 25.20) | 9.27 (8.41 to 19.88) |
Collected over Assessed every 4 weeks while on treatment and for 30 days after the end of treatment. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Arm A (Tipifarnib) | — | 52/72 (72.2%) | 50/72 (69.4%) |
| Arm B (Clinical Observation) | — | 8/69 (11.6%) | 23/69 (33.3%) |
| Event | Arm A (Tipifarnib) | Arm B (Clinical Observation) |
|---|---|---|
| Platelet count decreasedInvestigations | 36/72 | 6/69 |
| White blood cell decreasedInvestigations | 29/72 | 2/69 |
| Neutrophil count decreasedInvestigations | 25/72 | 0/69 |
| AnemiaBlood and lymphatic system disorders | 9/72 | 2/69 |
| Febrile neutropeniaBlood and lymphatic system disorders | 2/72 | 0/69 |
| ConfusionPsychiatric disorders | 2/72 | 0/69 |
| Acute coronary syndromeCardiac disorders | 1/72 | 0/69 |
| FatigueGeneral disorders | 1/72 | 0/69 |
| DiarrheaGastrointestinal disorders | 1/72 | 0/69 |
| NauseaGastrointestinal disorders | 1/72 | 0/69 |
| Event | Arm A (Tipifarnib) | Arm B (Clinical Observation) |
|---|---|---|
| White blood cell decreasedInvestigations | 42/72 | 12/69 |
| AnemiaBlood and lymphatic system disorders | 40/72 | 13/69 |
| Platelet count decreasedInvestigations | 39/72 | 11/69 |
| FatigueGeneral disorders | 5/72 | 1/69 |
| Rash maculo-papularSkin and subcutaneous tissue disorders | 5/72 | 0/69 |
| Neutrophil count decreasedInvestigations | 4/72 | 0/69 |
| MyalgiaMusculoskeletal and connective tissue disorders | 4/72 | 0/69 |
All randomized patients
| Age, Continuous(years) | Arm A (Tipifarnib) | Arm B (Clinical Observation) | Total |
|---|---|---|---|
| Median | 70 (30 to 86) | 69 (28 to 80) | 69 (28 to 86) |
| Sex: Female, Male(Participants) | Arm A (Tipifarnib) | Arm B (Clinical Observation) | Total |
|---|---|---|---|
| Female | 37 | 34 | 71 |
| Male | 36 | 37 | 73 |
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This study is completed, as verified in Jun 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Tipifarnib
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