A Randomized Multicenter Study to Compare the Safety and Efficacy of 166Ho-DOTMP Plus Melphalan to Melphalan Alone as Conditioning for Autologous Peripheral Blood Stem Cell Transplant in Subjects With Primary Refractory Multiple Myeloma
1.To determine the efficacy of STR (166Ho-DOTMP). The primary endpoint of this study is to
compare the CR rate at 6 months post-transplant (in the absence of further therapy) in
subjects with primary refractory multiple myeloma after treatment with 750 mCi/m2
166Ho-DOTMP plus 200 mg/m2 melphalan followed by autologous PBSCT to treatment with 200
mg/m2 melphalan alone followed by autologous PBSCT.
1. To compare the treatment groups with respect to survival and progression-free survival.
2. To compare treatment groups with respect to overall response rate (CR+VGPR+PR), best
response within 6 months, and duration of response.
3. To compare the safety profile of the treatment groups.
4. To assess the biodistribution and estimated radiation absorbed dose to kidney in the
first 20 subjects.
METHODOLOGY: Informed consent for participation in the study will be obtained, eligibility
determined, and the subject registered. All subjects will receive a tracer dose of 30 mCi
166Ho-DOTMP to determine skeletal uptake and biodistribution of 166Ho-DOTMP therapy.
Subjects may receive a therapy dose only if 1) the tracer dose shows no aberrant
distribution, and 2) if the skeletal residence time is at least 5.8 hours (equivalent to F x
Te > 4 hr). Subjects with adequate skeletal uptake and no aberrant distribution will be
stratified based on the length of time since first induction therapy, and on response to
prior therapy, and will undergo randomization to determine whether they will receive 166Ho
DOTMP plus melphalan (Arm A) or melphalan alone (Arm B) as the conditioning regimen prior to
Subjects randomized to Arm A will be treated with 750 mCi/m2 166Ho DOTMP intravenously 4 to
12 days after the tracer dose, with a total dosage not to exceed 1500 mCi. Five to 9 days
after the 166Ho-DOTMP therapy dose, subjects will receive 200 mg/m2 melphalan IV.
Subjects randomized to Arm B will receive 200 mg/m2 melphalan at least 10 days and no more
than 3 weeks after the tracer dose.
For all patients, cryopreserved hematopoietic stem cells will be infused 24 to 48 hours
after melphalan. Subjects will be followed for safety assessments for 10 years or until
death. Efficacy will be evaluated for up to 3 years in responding subjects, and disease
relapse or progression and survival will be documented until Year 10.
An analysis to estimate radiation dose to the kidney will be performed in the first 20
patients. Additionally, after 6 months of follow-up have been completed on the first 20
subjects in each arm, an analysis of the CR rate will be conducted to rule out lack of
efficacy of 166Ho-DOTMP. A planned interim analysis to determine the efficacy of the
treatment will be performed when 60 patients on each arm have completed 6 months of
follow-up. Enrollment on trial will continue while these interim analyses are performed.
NUMBER OF SUBJECTS: Two hundred and forty subjects who meet the eligibility criteria and
receive study treatment will be followed on this protocol.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
United States: Food and Drug Administration
|University of Alabama||Birmingham, Alabama|
|MD Anderson Cancer Center||Houston, Texas 77030-4096|
|Fred Hutchinson Cancer Research Center||Seattle, Washington 98109|
|Medical College of Wisconsin||Milwaukee, Wisconsin 53226|
|University of Kansas Medical Center||Kansas City, Kansas 66160-7353|
|University of Nebraska Medical Center||Omaha, Nebraska 68198-3330|
|Winship Cancer Institute of Emory University||Atlanta, Georgia 30322|
|Montefiore Medical Center||Bronx, New York 10467-2490|
|Baylor University Medical Center||Dallas, Texas 75246|
|Vanderbilt University Medical Center||Nashville, Tennessee 37232-2516|
|Miami Valley Hospital||Dayton, Ohio 45409|
|Rocky Mountain Cancer Centers||Thornton, Colorado 80260|
|University of Pennsylvania||Philadelphia, Pennsylvania 19104|
|Duke University Medical Center||Durham, North Carolina 27710|
|Case Western Reserve University||Cleveland, Ohio 44106|
|University of Miami||Miami, Florida 33136|
|Virginia Commonwealth University||Richmond, Virginia|
|Chao Family Comprehensive Cancer Center, University of California, Irvine||Orange, California 92868|
|University of Iowa Hospital and Clinics||Iowa City, Iowa 52242|
|Wayne State University, Barbara Ann Karmanos Cancer Institute||Detroit, Michigan 48201|