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

Sponsored by:	Schering-Plough
Information provided by:	Schering-Plough
ClinicalTrials.gov Identifier:	NCT00109538

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 III

MedlinePlus related topics: Blood Transfusion and Donation Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Lonafarnib

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
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

Further study details as provided by Schering-Plough:

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 ]

Estimated Enrollment:	200
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
Lonafarnib: Experimental 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
Placebo: Placebo Comparator 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

No Contacts or Locations Provided

More Information

Responsible Party:	Schering-Plough ( Susan Arbuck, MD - Vice President, Global Clinical Research, Oncology )
Study ID Numbers:	P02978
Study First Received:	April 28, 2005
Last Updated:	October 29, 2008
ClinicalTrials.gov Identifier:	NCT00109538
Health Authority:	United States: Food and Drug Administration

Keywords provided by Schering-Plough:

Lonafarnib

Study placed in the following topic categories:

Myelodysplastic syndromes
Neural Tube Defects
Precancerous Conditions
Chronic myelomonocytic leukemia
Nervous System Malformations
Hematologic Diseases
Leukemia, Myelomonocytic, Chronic
Myelodysplasia
Myelodysplastic Syndromes
Anemia

Myeloproliferative Disorders
Leukemia, Myeloid
Leukemia, Myelomonocytic, Acute
Myelodysplastic myeloproliferative disease
Leukemia
Preleukemia
Neural tube defect, folate-sensitive
Congenital Abnormalities
Myelodysplastic-Myeloproliferative Diseases
Bone Marrow Diseases

Additional relevant MeSH terms:

Neoplasms
Pathologic Processes
Disease

Neoplasms by Histologic Type
Syndrome
Nervous System Diseases

ClinicalTrials.gov processed this record on January 15, 2009