Study Comparing STR (Skeletal Targeted Radiotherapy) Plus Melphalan to Melphalan Alone, With Stem Cell Transplant in Multiple Myeloma
|First Submitted Date ICMJE||May 25, 2004|
|First Posted Date ICMJE||May 28, 2004|
|Last Update Posted Date||March 31, 2009|
|Start Date ICMJE||March 2004|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00083564 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Study Comparing STR (Skeletal Targeted Radiotherapy) Plus Melphalan to Melphalan Alone, With Stem Cell Transplant in Multiple Myeloma|
|Official Title ICMJE||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|
STR (Skeletal Targeted Radiotherapy, 166Ho-DOTMP) is an investigational radiopharmaceutical that delivers radiation directly to cancer cells in the bone and bone marrow. Conventional methods of delivering radiation therapy, such as total body irradiation, expose non-target tissues to radiation and cause serious side effects. In contrast, STR's targeted approach to delivering radiotherapy concentrates the radiation where it is needed, and minimizes exposure of normal tissues.
STR is composed of a bone-targeting molecule, DOTMP, in a stable complex with the radionuclide holmium-166. When injected into a patient's bloodstream, STR rapidly binds to bone mineral, delivering a brief, intense dose of radiation to destroy cancer cells in the bone and marrow. The high-energy and long path-length of holmium-166 beta particles provide optimal penetration and uniform irradiation of disease sites in the marrow and bone. STR that does not bind to bone is rapidly eliminated through the urinary tract. STR treatment is followed by autologous stem cell transplantation. The short half-life of holmium-166 allows treatment on an out-patient basis, and minimizes the time required between STR administration and transplantation.
The phase III study of STR is a multi-center, randomized, controlled study, designed to evaluate the safety and efficacy of STR in patients with primary refractory multiple myeloma. These are patients who have failed to achieve at least a partial response to conventional therapy and have been undergoing treatment for less than 18 months. The trial is expected to enroll approximately 240 evaluable patients, half on the experimental arm and half on the control arm. Patients on the experimental arm will receive STR at a dose of 750 mCi/m2 plus the chemotherapy drug melphalan at 200 mg/m2, followed by autologous stem cell transplantation. Patients on the control arm will receive melphalan only, followed by transplantation. Patients on both study arms will be evaluated for response to treatment six months after transplantation, using an immunofixation assay to detect myeloma protein in patient samples. Analysis of patient samples will be conducted at a central laboratory, and blinded results will be reviewed by an independent panel of experts. The study's primary endpoint is complete response, as determined by the complete disappearance of myeloma protein at six months post-transplant.
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.
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 autologous PBSCT.
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.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 3|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Condition ICMJE||Multiple Myeloma|
|Intervention ICMJE||Drug: STR(TM) (Skeletal Targeted Radiotherapy, Holmium-166-DOTMP)|
|Study Arms||Not Provided|
|Publications *||Giralt S, Bensinger W, Goodman M, Podoloff D, Eary J, Wendt R, Alexanian R, Weber D, Maloney D, Holmberg L, Rajandran J, Breitz H, Ghalie R, Champlin R. 166Ho-DOTMP plus melphalan followed by peripheral blood stem cell transplantation in patients with multiple myeloma: results of two phase 1/2 trials. Blood. 2003 Oct 1;102(7):2684-91. Epub 2003 May 1.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Terminated|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
A subject must meet all of the following criteria to be eligible for the study. These will be evaluated within four weeks prior to enrollment.
A subject meeting any of the following criteria is not eligible for participation in the study:
|Ages||18 Years to 70 Years (Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Canada, United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00083564|
|Other Study ID Numbers ICMJE||STR 0303|
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||Poniard Pharmaceuticals|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|PRS Account||Poniard Pharmaceuticals|
|Verification Date||March 2009|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP