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

NCT00109538 | Terminated Phase 3 DMC

• 1 other identifier: P02978
• Study Type: interventional
• Target: 47
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic; Myelodysplasia; Myelomonocytic

Keywords

Lonafarnib

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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

Study Arms (2)

Lonafarnib

EXPERIMENTAL

Lonafarnib 200 mg twice daily, oral, continuously

Drug: Lonafarnib

Placebo

PLACEBO COMPARATOR

Placebo, BID, oral

Other: Placebo

Interventions

Lonafarnib DRUG

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

Also known as: SCH 66336

Lonafarnib

Placebo OTHER

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic; Anemia, Refractory, with Excess of Blasts

Interventions

lonafarnib

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Anemia, Refractory; Anemia

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2005
• First Posted: April 29, 2005
• Study Start: May 1, 2005
• Primary Completion: August 1, 2008
• Study Completion: August 1, 2008
• Last Updated: May 1, 2015

Record last verified: 2015-04