- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00329030
Rituxan/BEAM vs Bexxar/BEAM in Autologous Hematopoietic Stem Cell Transplant for Non-Hodgkin's Lymphoma (BMTCTN0401)
Phase III Rituxan/BEAM vs. Bexxar/BEAM With Autologous Hematopoietic Stem Cell Transplantation (ASCT) for Persistent or Relapsed Chemotherapy Sensitive Diffuse Large B-cell Non-Hodgkin's Lymphoma (BMTCTN0401)
Study Overview
Status
Intervention / Treatment
Detailed Description
BACKGROUND:
Bexxar (Tositumomab and Iodine I 131 Tositumomab) is a radioimmunoconjugate with demonstrated anti-lymphoma effects. This drug is indicated for the treatment of patients with CD20 positive, relapsed or refractory, low grade, follicular, or transformed non-Hodgkin's lymphoma, including patients with Rituximab-refractory non-Hodgkin's lymphoma. Bexxar has been used in several Phase I and II transplant trials either alone or in combination with high-dose chemotherapy for the treatment of relapsed non-Hodgkin's lymphoma. The Phase I and II trials combining Bexxar with BEAM and autologous hematopoietic stem cell transplantation demonstrated promising early results with 80% event-free survival in relapsed chemosensitive diffuse large B-cell non-Hodgkin's lymphoma patients. The administration of Rituxan to the mobilization and conditioning regimen is now the standard of care at most transplant centers. Therefore, the primary endpoint of this study will be to compare progression-free survival after autologous hematopoietic stem cell transplantation for chemotherapy-sensitive diffuse large B-cell lymphoma using Rituxan/BEAM versus Bexxar/BEAM for pre-transplant conditioning.
DESIGN NARRATIVE:
All patients will receive induction or salvage chemotherapy as indicated by their clinical circumstance to achieve at least a partial response (as defined in the protocol). There must be 20% or less bone marrow involvement after their most recent salvage therapy.
Mobilization therapy may be employed per institutional guidelines, but all patients must receive one dose of rituxan (375 mg/m^2) at least within 4 weeks of actual stem cell apheresis. Patients must have an adequate autograft (target of at least 2.0 X 10^6 CD34+ cells/kg; minimum of more than 1.5 X 106 CD34+ cells/kg) to be eligible for the protocol. Eligible patients will be randomized to receive either: 1) Rituxan plus BEAM, with Rituxan 375 mg/m^2 IV Days -19 and -12, Carmustine (BCNU) 300 mg/m^2 Day -6, Etoposide 100 mg/m^2 Days -5 to -2, Cytarabine 100 mg/m^2 Days -5 to -2, and Melphalan 140 mg/m^2 Day -1 followed by ASCT; or, 2) Bexxar/BEAM with the dosimetric dose of 5 mCi Bexxar on Day -19 and the therapeutic dose calculated to administer 75 cGy total body dose (TBD) on Day -12. Patients will then receive BCNU 300 mg/m^2 Day -6, Etoposide 100 mg/m^2 Days -5 to -2, Cytarabine 100 mg/m^2 Days -5 to -2, and Melphalan 140 mg/m^2 Day -1 followed by ASCT.
Patients will be followed for 2 years post-transplant. Survival data, hematopoiesis data, incidence of infection, mucositis assessment data, immune reconstitution data, and toxicity data will be recorded and reported periodically to the BMT CTN Data Coordinating Center (DCC).
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Connecticut
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New Haven, Connecticut, United States, 06520
- Yale University School Of Medicine
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Florida
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Gainesville, Florida, United States, 32610
- University of Florida College of Medicine (Shands)
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Miami, Florida, United States, 33136
- University of Miami
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Tampa, Florida, United States, 33624
- H. Lee Moffitt Cancer Center
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Georgia
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Atlanta, Georgia, United States, 30322
- Emory University
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Idaho
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Boise, Idaho, United States, 83712
- St. Lukes Mountain States Tumor Institute
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Illinois
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Maywood, Illinois, United States, 60153
- Loyola University Medical Center
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Iowa
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Iowa City, Iowa, United States, 52242
- University of Iowa Hospitals and Clinics
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Maryland
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Baltimore, Maryland, United States, 21231
- Johns Hopkins/SKCCC
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Baltimore, Maryland, United States, 21228
- University of Maryland Medical Systems/Greenbaum Cancer Center
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Massachusetts
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Boston, Massachusetts, United States, 02111
- Tufts-New England Medical Center
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Michigan
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Ann Arbor, Michigan, United States, 48109
- University of Michigan Medical Center
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Minnesota
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Minneapolis, Minnesota, United States, 55455
- University of Minnesota
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Missouri
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Saint Louis, Missouri, United States, 63110
- Washington University/Barnes Jewish Hospital
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Nebraska
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Omaha, Nebraska, United States, 68198
- University of Nebraska
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New Jersey
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Hackensack, New Jersey, United States, 07601
- Hackensack University Medical Center
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New York
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New York, New York, United States, 10021
- Memorial Sloan-Kettering Cancer Center
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New York, New York, United States, 10065
- Weill Cornell Medical College, The New York Presbyterian Hospital
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Rochester, New York, United States, 14642
- University of Rochester Medical Center
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North Carolina
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Chapel Hill, North Carolina, United States, 27599
- University of North Carolina Hospital at Chapel Hill
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Durham, North Carolina, United States, 27705
- Duke University Medical Center
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Ohio
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Cleveland, Ohio, United States, 44106
- University Hospitals of Cleveland/Case Western
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Oregon
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Portland, Oregon, United States, 97213
- Providence Portland Medical Center
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Portland, Oregon, United States, 97225
- Columbia River Oncology Program
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- University of Pennsylvania Cancer Center
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South Carolina
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Charleston, South Carolina, United States, 29425
- Medical University of South Carolina
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Greenville, South Carolina, United States, 29615
- Cancer Centers of the Carolinas
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Tennessee
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Nashville, Tennessee, United States, 37232
- Vanderbilt University Medical Center
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Texas
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Dallas, Texas, United States, 75246
- Baylor University Medical Center
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San Antonio, Texas, United States, 78229
- Texas Transplant Institute
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Utah
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Salt Lake City, Utah, United States, 84132
- University of Utah Medical School, BMT
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Salt Lake City, Utah, United States, 84143
- Intermountain BMT Program
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Virginia
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Richmond, Virginia, United States, 23298
- Virginia Commonwealth University/MCV Hospital
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Washington
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Seattle, Washington, United States, 98109
- Fred Hutchinson Cancer Research Center
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Wisconsin
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Madison, Wisconsin, United States, 53792
- University of Wisconsin Hospital and Clinics
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Milwaukee, Wisconsin, United States, 53211
- Medical College Of Wisconsin
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Diagnosis of persistent or recurrent REAL classification diffuse large B-cell lymphoma, composite lymphoma with more than 50% diffuse large B-cell lymphoma, mediastinal B-cell lymphoma
- Demonstration of CD20+ on at least one histologic specimen
- 18-80 years old at time of first registration
- Three or fewer prior regimens of chemotherapy over the entire course of their disease treatment (including one induction chemotherapy and no more than 2 salvage chemotherapies); monoclonal antibody therapy and involved field radiation therapy will not be counted as prior therapies
- Disease status of primary induction failure, first relapse, or second complete remission; all patients must have chemosensitive disease as demonstrated by response to induction or salvage chemotherapy with at least a partial response (as defined in the protocol)
- No more than a 20% bone marrow involvement
- Patients with adequate organ function as measured by:
- Cardiac: American Heart Association Class I: Patients with cardiac disease but without resulting limitation of physical activity; ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain; additionally, patients greater than 60 years of age must have a left ventricular ejection fraction at rest of at least 40% demonstrated by Multi-Gated Acquisition Scan (MUGA)
- Hepatic: Bilirubin less than 2.0 mg/dL (except for isolated hyperbilirubinemia attributed to Gilbert syndrome) and alanine transaminase (ALT) and aspartate transaminase (AST) less than 3x the upper limit of normal
- Renal: Creatinine less than 2.0 mg/dL or creatinine clearance (calculated creatinine clearance is permitted) more than 40 mL/min; no hydronephrosis on CT scan prior to mobilization
- Pulmonary: Carbon Monoxide Diffusing Capacity (DLCO), Volume forcibly exhaled in one second (FEV1), forced vital capacity (FVC) at least 45% of predicted (corrected for hemoglobin)
- Autologous graft with a minimum of at least 1.5 X 10^6 CD34+ cells/kg (target greater than 2.0 X 10^6 CD34+ cells/kg. Peripheral blood stem cells (PBSC) are preferred; however, if PBSC mobilization fails, cells can be obtained by institutional practices (in cases where bone marrow will be used for transplantation, the required CD34+ dose does not apply and institutional practice for total nucleated cell dose should be used).
- Initiate conditioning therapy within 3 months of mobilization
- Signed informed consent
Exclusion Criteria:
- Karnofsky performance score less than 70%
- Transformed follicular lymphoma
- Uncontrolled bacterial, viral, or fungal infection (currently taking medication and with progression or no clinical improvement)
- Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ; cancer treated with curative intent less than 5 years previously will not be allowed unless approved by the Medical Monitor or Protocol Chair; cancer treated with curative intent less than 5 years previously will be allowed
- Pregnant (positive β-HCG) or breastfeeding; this patient population is excluded due to the lack of data on the use of Bexxar in patients who are pregnant or breastfeeding
- Seropositivity for HIV; this patient population is excluded due to the lack of data on the use of Bexxar in HIV positive patients and because the treatment regimens are too immunosuppressive for this patient population
- Fertile men or women unwilling to use contraceptive techniques from the time of initiation of mobilization until six-months post-transplant
- Prior autologous or allogeneic hematopoietic stem cell transplantation (HSCT)
- Patients with evidence of myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) or abnormal cytogenetic analysis indicative of MDS on the pre-transplant bone marrow examination
- Patients with a prior severe reaction to Rituxan or Filgrastim (G-CSF). Patients with severe reactions to G-CSF that receive pre-medication for control of the reaction are not excluded from study.
- Patients who have received prior radioimmunotherapy
- Patients with known hypersensitivity to murine proteins
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: Rituxan/BEAM
Autologous transplantation using rituxan/BEAM
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Rituxan 375 mg/m2 (Day -19 and Day -12); BCNU 300 mg/m2 (Day -6); Etoposide (VP-16) 100 mg/m2 twice a day (Days -5 to -2); Cytarabine 100 mg/m2 twice a day (Days -5 to -2); Melphalan 140 mg/m2 (Day -1); Followed by autologous transplantation
Other Names:
|
EXPERIMENTAL: Bexxar/BEAM
Autologous transplantation using Bexxar/BEAM
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Bexxar dosimetric dose 5 mCi (Day -19); Bexxar therapy dose 75 cGy TBD (Day -12); BCNU 300 mg/m2 (Day -6); Etoposide (VP-16) 100 mg/m2 twice a day (Days -5 to -2); Cytarabine 100 mg/m2 twice a day (Days -5 to -2); Melphalan 140 mg/m2 (Day -1); Followed by autologous transplantation
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free Survival (PFS)
Time Frame: 1 and 2 years
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Patients are considered a failure for this endpoint if they die, relapse/progress, or receive anti-lymphoma therapy, other than post-transplant consolidative localized radiation (maximum 3 sites) to sites of prior bulk disease pre-transplant (> 3cm).
The time to this event is the time from randomization until death, relapse/progression, receipt of anti-lymphoma therapy, or last follow up, whichever comes first.
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1 and 2 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival
Time Frame: 1 and 2 years
|
The event is death from any cause.
The time to this event is the time from randomization to death or last follow-up.
Surviving patients are censored at the time of last observation
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1 and 2 years
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Incidence of Relapse/Progression
Time Frame: 1 and 2 years
|
The time to this event is measured from randomization.
Deaths without relapse/progression are considered as a competing risk.
Surviving patients with no history of relapse/progression are censored at time of last follow-up.
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1 and 2 years
|
Complete Response (CR) and Partial Response (PR) Proportion
Time Frame: Day 100 and 2 years
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Day 100 and 2 years
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Platelet Recovery to 20,000 Cells/μL
Time Frame: 100 and 180 days
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100 and 180 days
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Hematologic Function
Time Frame: 100 days, 1 year
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Hematologic function will be defined as ANC > 1,500 neutrophils/μL, hemoglobin > 10 g/dL without transfusion support, and platelet count > 100,000/μL without transfusion support.
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100 days, 1 year
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Incidence of Infection
Time Frame: 1 year
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1 year
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Mucositis Severity
Time Frame: Day 21
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Mucositis severity will be scored per the modified Oral Mucositis Assessment Scale (OMAS) scoring system on a scale of 0 - 4, where 0 equals normal mucosa and 4 equals severe mucosa.
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Day 21
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Immune Reconstitution
Time Frame: 1 year
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Tests to be performed on peripheral blood include CD2, CD3, CD4, CD8, CD19, CD3+/CD25+, CD45 RA/RO, CD56+/CD3-.
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1 year
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Immune Reconstitution of Quantitative Immunoglobulins
Time Frame: 1 year
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Tests to be performed on peripheral blood for quantitative immunoglobulins include IgM, IgG and IgA.
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1 year
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Treatment-related Mortality (TRM)
Time Frame: 1 and 2 years
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TRM is defined as death occurring in a patient from causes other than relapse or progression
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1 and 2 years
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Neutrophil Recovery
Time Frame: Day 28 and Day 60
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Time to neutrophil recovery will be the first of two consecutive days of > 500 neutrophils/μL following the expected nadir.
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Day 28 and Day 60
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Collaborators and Investigators
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Large B-Cell, Diffuse
- Lymphoma
- Lymphoma, B-Cell
- Lymphoma, Non-Hodgkin
- Lymphoma, Large-Cell, Immunoblastic
- Plasmablastic Lymphoma
- Physiological Effects of Drugs
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Rituximab
- Tositumomab I-131
Other Study ID Numbers
- BMTCTN0401
- U01HL069294-05 (NIH)
- BMT CTN 0401 (OTHER: Blood and Marrow Transplant Clinicial Trials Network)
- 384 (OTHER: BMT CTN)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- ICF
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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