Ignite Creation Date:
2024-05-05 @ 11:35 AM
Last Modification Date:
2024-10-26 @ 9:10 AM
Study NCT ID:
NCT00083564
Status:
TERMINATED
Last Update Posted:
2009-03-31
First Post:
2004-05-25
Brief Title:
Study Comparing STR Skeletal Targeted Radiotherapy Plus Melphalan to Melphalan Alone With Stem Cell Transplant in Multiple Myeloma
Sponsor:
Poniard Pharmaceuticals
Organization:
Poniard Pharmaceuticals
Study Overview
Official Title:
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
Status:
TERMINATED
Status Verified Date:
2009-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
For business reasons
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 STRs 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 patients 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 mCim2 plus the chemotherapy drug melphalan at 200 mgm2 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 studys primary endpoint is complete response as determined by the complete disappearance of myeloma protein at six months post-transplant
STR is composed of a bone-targeting molecule DOTMP in a stable complex with the radionuclide holmium-166 When injected into a patients 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 mCim2 plus the chemotherapy drug melphalan at 200 mgm2 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 studys primary endpoint is complete response as determined by the complete disappearance of myeloma protein at six months post-transplant
Detailed Description:
PRIMARY OBJECTIVE
1To 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 mCim2 166Ho-DOTMP plus 200 mgm2 melphalan followed by autologous PBSCT to treatment with 200 mgm2 melphalan alone followed by autologous PBSCT
SECONDARY OBJECTIVES
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 CRVGPRPR 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 58 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 mCim2 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 mgm2 melphalan IV
Subjects randomized to Arm B will receive 200 mgm2 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
1To 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 mCim2 166Ho-DOTMP plus 200 mgm2 melphalan followed by autologous PBSCT to treatment with 200 mgm2 melphalan alone followed by autologous PBSCT
SECONDARY OBJECTIVES
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 CRVGPRPR 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 58 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 mCim2 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 mgm2 melphalan IV
Subjects randomized to Arm B will receive 200 mgm2 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None