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

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

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.

Study Overview

• Status: Terminated
• Conditions: Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic; Myelodysplasia; Myelomonocytic
• Intervention / Treatment: Drug: Lonafarnib; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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.	Any 8-consecutive week period after randomization

Secondary Outcome Measures

Outcome Measure	Time Frame
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.	Any 8-consecutive week period after randomization

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: April 28, 2005
• First Submitted That Met QC Criteria: April 28, 2005
• First Posted (Estimate): April 29, 2005

Study Record Updates

• Last Update Posted (Estimate): May 1, 2015
• Last Update Submitted That Met QC Criteria: April 9, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Lonafarnib
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Myeloid; Syndrome; Myelodysplastic Syndromes; Leukemia; Preleukemia; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Lonafarnib
• Other Study ID Numbers: P02978