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Phase I Study of the Farnesyl Transferase Inhibitor R115777 (NSC #702818) in Patients With Myelodysplastic Syndrome

Phase 1
18 Years
Not Enrolling
Chronic Myelomonocytic Leukemia, de Novo Myelodysplastic Syndromes, Previously Treated Myelodysplastic Syndromes, Refractory Anemia, Refractory Anemia With Excess Blasts, Refractory Anemia With Excess Blasts in Transformation, Refractory Anemia With Ringed Sideroblasts, Refractory Cytopenia With Multilineage Dysplasia

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Trial Information

Phase I Study of the Farnesyl Transferase Inhibitor R115777 (NSC #702818) in Patients With Myelodysplastic Syndrome


I. To determine the toxicity profile and antitumor activity of the farnesyltransferase
(FTase) inhibitor R115777 (tipifarnib) in patients with myelodysplastic syndrome (MDS)
treated on a one week on/one week off schedule.

II. To determine the effect on R115777 on a one week on/one week off schedule on FTase
activity, prenylation of RAS and other substrates and on downstream effects.

OUTLINE: This is a dose-escalation study.

Patients receive tipifarnib orally (PO) twice daily (BID) on weeks 1, 3, 5, and 7. Treatment
repeats every 8 weeks for up to 2 courses in the absence of disease progression or
unacceptable toxicity.

Inclusion Criteria:

- Patients must have histologically MDS (including French-American-British [FAB] types
refractory anemia [RA], refractory anemia with ringed sideroblasts [RARS], refractory
anemia with excess blasts [RAEB], refractory anemia with excess blasts in
transformation [RAEBT], or chronic myelomonocytic leukemia [CMMoL]); for the purpose
of the study, all patients will be classified by World Health Organization (WHO)

- By these criteria, FAB RA are split into:

- Pure dyserythropoietic refractory anemia (PRA)

- Refractory cytopenia with multilineage dysplasia (RCMD)

- FAB RARS is split into:

- Pure sideroblastic anemia (PSA)

- Refractory sideroblastic cytopenia with multilineage dysplasia (RSCMD)

- FAB RAEB is split into:

- RAEB I (< 10% BM blasts)

- RAEB II (10-20% BM blasts)

- Patients with CMMoL, and RAEBT by FAB classification will be included in the

- Prognosis will be assessed by International Prognostic Scoring System (IPSS) criteria

- =< 2 prior therapies

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2

- Life expectancy of greater than 12 weeks

- Bilirubin =< 1.5mg %

- Creatinine =< 1.5mg %

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control) prior to study entry and for the
duration of study participation; should a woman become pregnant or suspect she is
pregnant while participating in this study, she should inform her treating physician

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks (3 months for
UCN01) prior to entering the study or those who have not recovered from adverse
events due to agents administered more than 4 weeks earlier

- Patients may not be receiving any other investigational agents

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to R115777 (such as imidazoles)

- Patients eligible for bone marrow transplant (=< 60 years old), with a compatible
sibling, no contraindications for transplant

- Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Pregnant women are excluded from this study; breastfeeding should be discontinued if
the mother is treated with R115777.

- Growth factors other than filgrastim (G-CSF) are excluded; patients should be off
excluded growth factors for 2 weeks

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

MTD defined as the next lower dose level at which 2 patients experience dose limiting toxicity (DLT) defined as grade 3 or 4 toxicity according to the Cancer Therapy Evaluation Program Common Toxicity Criteria

Outcome Description:

The final analysis will report all toxicities by grade, dose, cycle, and by cumulative dose.

Outcome Time Frame:

Up to 8.5 years

Safety Issue:


Principal Investigator

Razelle Kurzrock

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

June 2002

Completion Date:

Related Keywords:

  • Chronic Myelomonocytic Leukemia
  • de Novo Myelodysplastic Syndromes
  • Previously Treated Myelodysplastic Syndromes
  • Refractory Anemia
  • Refractory Anemia With Excess Blasts
  • Refractory Anemia With Excess Blasts in Transformation
  • Refractory Anemia With Ringed Sideroblasts
  • Refractory Cytopenia With Multilineage Dysplasia
  • Anemia
  • Anemia, Refractory
  • Anemia, Refractory, with Excess of Blasts
  • Leukemia
  • Leukemia, Myelomonocytic, Chronic
  • Myelodysplastic Syndromes
  • Preleukemia
  • Leukemia, Myelomonocytic, Acute
  • Anemia, Aplastic



M D Anderson Cancer Center Houston, Texas  77030