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

Myelodysplastic Syndromes Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00109538
• Other study ID #: P02978
• Status: Terminated
• Phase: Phase 3
• First received: April 28, 2005
• Last updated: April 9, 2015
• Start date: May 2005
• Est. completion date: August 2008

Study information

• Verified date: April 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 47
• Est. completion date: August 2008
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myelomonocytic, Acute
• Leukemia, Myelomonocytic, Chronic
• Myelodysplasia
• Myelodysplastic Syndromes
• Myelomonocytic
• Preleukemia
• Syndrome

Intervention

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:
• Placebo
BID, oral, continuously, or until unacceptable toxicity or transformation to AML, or disease progression, or other discontinuation criteria

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes