Study of Lonafarnib Versus Placebo in Subjects With Either Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) (Study P02978AM3)(TERMINATED)

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00109538
First received: April 28, 2005
Last updated: October 24, 2013
Last verified: October 2013
  Purpose

The purpose of this study is to assess the benefit of lonafarnib (versus placebo) in patients with myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML). Benefit will be measured by achievement of platelet transfusion independence for at least 8-consecutive weeks, and without simultaneous worsening of hemoglobin and/or need for red blood cell (RBC) transfusion. Additional endpoints will be hematologic response (which includes complete remission, partial remission, hematologic improvement), number of RBC transfusions, bleeding events, infections and safety.


Condition Intervention Phase
Myelodysplastic Syndromes
Leukemia, Myelomonocytic, Chronic
Myelodysplasia
Myelomonocytic
Drug: Lonafarnib
Other: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Pivotal Randomized Study of Lonafarnib Versus Placebo in the Treatment of Subjects With Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) Who Are Platelet Transfusion Dependent With or Without Anemia

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Proportion of subjects who achieved platelet transfusion independence for any 8-consecutive week period after randomization without worsening of RBC transfusion requirements or hemoglobin (untransfused) during the same 8-consecutive-week period. [ Time Frame: Any 8-consecutive week period after randomization ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Hematologic response rate (CR, PR, HI), number of RBC transfusion events during a 4-week period, active bleeding events (number and severity), number of CTCAE Grade 3 and 4 infections and days of acute intervention, and safety. [ Time Frame: Any 8-consecutive week period after randomization ] [ Designated as safety issue: Yes ]

Enrollment: 47
Study Start Date: May 2005
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lonafarnib
Lonafarnib 200 mg twice daily, oral, continuously
Drug: Lonafarnib
200 mg twice daily (BID, ie, approximately 12 hours apart with food), oral, continuously, or until unacceptable toxicity or transformation to AML, or disease progression, or other discontinuation criteria
Other Name: SCH 66336
Placebo Comparator: Placebo
Placebo, BID, oral
Other: Placebo
BID, oral, continuously, or until unacceptable toxicity or transformation to AML, or disease progression, or other discontinuation criteria

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed MDS (RA, RARS, RAEB, RAEB-T) or CMML according to FAB classification.
  • Platelet transfusion dependence (requiring 1 to 8 platelet transfusion events every 4 week period (Day 84 to Day 57, Day 56 to Day 29, and Day 28 to Day 1) over an 8-week retrospective and 4-week prospective screening period).
  • The individual number of platelet transfusion events during the three 4-weekly periods (Day 84 to Day -57; Day -56 to Day 29; Day -28 to Day -1) must not differ by greater more than 2 from the average number of platelet transfusion events during the 12 week screening period.
  • If the subject is RBC transfusion dependent, the number of RBC transfusion events during the three 4-weekly periods (Days -84 to -57; Day -56 to Day 29 and Day -28 to Day -1) must not differ by more than 2 from the average number of RBC transfusion events during this 12 week screening period.

ECOG PS 0-2.

Exclusion Criteria:

  • Subjects with chemotherapy/radiotherapy-associated secondary MDS.
  • <12 Weeks (prior to Day-1 Randomization) from any investigational drug use, any chemotherapy, radiotherapy, immunotherapy and any other treatment or MDS/CMML other than best supportive care.
  • Hx of bone-marrow or peripheral stem-cell transplantation or treatment with donor lymphocyte infusion.
  • Hx of AML.
  • Known hx of immune thrombocytopenic purpura.
  • Marked baseline prolongation of QTc interval, CTCAE Grade >=1.
  • Use of ketokonazole within 72 hours prior to study drug administration.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00109538     History of Changes
Other Study ID Numbers: P02978
Study First Received: April 28, 2005
Last Updated: October 24, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
Lonafarnib

Additional relevant MeSH terms:
Leukemia
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Leukemia, Myeloid
Myelodysplastic-Myeloproliferative Diseases
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions

ClinicalTrials.gov processed this record on October 20, 2014