Nonmyeloablative Allogeneic Stem Cell Transplant Followed by Bortezomib in High-risk Multiple Myeloma Patients
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|ClinicalTrials.gov Identifier: NCT02308280|
Recruitment Status : Active, not recruiting
First Posted : December 4, 2014
Last Update Posted : October 18, 2018
Multiple myeloma is a morbid disease associated with a poor outcome, particularly those with high-risk cytogenetics. While standard therapies have modestly improved survival in these high-risk patients, myeloma remains incurable. To date, the only potential curative treatment remains allogeneic hematopoietic stem cell transplantation. However, the high incidences of toxicities including chronic GVHD and disease progression are currently the two most important obstacles to this therapy. Better approaches to maintain and improve benefits of allogeneic transplant, while decreasing toxicity, are urgently needed.
The investigators hypothesize that Bortezomib administration after non myeloablative allogeneic hematopoietic stem cell transplantation in high-risk myeloma patients might improved the outcome of these patients by decreasing myeloma relapse and the severity of chronic GVHD while preserving the graft-versus-myeloma effect. Our goal is to improve the poor clinical outcome of high-risk myeloma patients.
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma High-Risk Cancer||Drug: Bortezomib following nonmyeloablative allogeneic transplant||Phase 2|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II, Open-label Study of Bortezomib Following Nonmyeloablative Allogeneic Stem Cell Transplant in Patients With High-risk Multiple Myeloma|
|Study Start Date :||November 2014|
|Estimated Primary Completion Date :||November 2019|
|Estimated Study Completion Date :||November 2022|
Experimental: Bortezomib post-transplantation
Non myeloablative allogeneic transplantation followed by Bortezomib for 1 year after a Bortezomib-based induction and autologous stem cell transplantation.
Bortezomib: 1,3 mg/m2 subcutaneously every 2 weeks for 26 injections.
Drug: Bortezomib following nonmyeloablative allogeneic transplant
Bortezomib 1,3 mg/m2 subcutaneously every 2 weeks for 1 year (26 injections) starting on day +120 from a non myeloablative sibling or 10/10 unrelated allogeneic transplantation
Other Name: Velcade
- Progression-free survival [ Time Frame: At 2 years after allogeneic transplantation ]Progression-free survival is defined as the duration from start of the treatment to disease progression or death (regardless of cause of death), whichever comes first. A 2- sided confidence interval for this proportion will be computed. Minimal residual disease results from negativity to positivity using flow cytometry will not be used to define progression.
- Incidence of ≥ grade III non hematologic toxicity (including ≥ grade II peripheral neuropathy) and incidence of ≥ grade IV hematologic toxicity [ Time Frame: At each medical visit up to 5 years from allogeneic transplantation ]Non hematologic toxicity and hematologic toxicity will be graded according to CTCAE v.4.0.
- Cumulative incidence of grade I-IV and grade II-IV acute GVHD [ Time Frame: At day 100 days, 6 months and 1 year after allogeneic transplantation ]Acute GVHD will be graded according to modified Glucksberg criteria
- Cumulative incidences of chronic GVHD [ Time Frame: At 1 and 2 years after allogeneic transplantation ]Chronic GVHD will be evaluated according to NIH criteria
- Maximum grades of acute and chronic GVHD [ Time Frame: At each medical visit up to 5 years from allogeneic transplantation ]Acute and chronic GVHD evaluation will based on modified Glucksberg and NIH criteria, respectively
- Response rates and quality of responses [ Time Frame: Before allogeneic transplantation, before bortezomib, 1 year after bortezomib, then every 8 to 12 weeks up to 5 years from allogeneic transplantation ]Response categories will be assessed based on the IMWG criteria
- Nonrelapse mortality [ Time Frame: At 100 days and 2 years ]Nonrelapse mortality is defined as time to deaths without relapse or recurrence. Deaths from any cause without prior progression are events.
- Overall survival [ Time Frame: At 2 years ]Overall survival is defined as time to death, irrespective of the cause.
- Incidence of relapse [ Time Frame: At 2 years ]Relapse is defined as progression of the disease previously treated, based on the IMWG criteria.
- Minimal residual disease on bone marrow using multiparametric flow cytometry [ Time Frame: Before the allogeneic transplantation, before Bortezomib administration (day +120), at 3, 6, 9, 12, 15, 18, 21 and 24 months from day +120 of the allogeneic transplantation ]From ≥ 5 million events, specimens with less than 50 aberrant phenotype plasma cells will be considered as MRD negative
- Quality of life after allogeneic transplantation [ Time Frame: Evaluated before allogeneic transplantation, at 100 days from transplantation, before Bortezomib administration, then every 3 months up to 5 years from allogeneic transplantation ]Quality of life will be assessed prospectively by the EORTC QLQ-MY20, EORTC QLQ-C30 (version 3) and FACT-BMT (version 4) questionnaires
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02308280
|Montreal, Quebec, Canada, H1T 2M4|
|Principal Investigator:||Richard LeBlanc, M.D.||Hôpital Maisonneuve-Rosemont, affiliated to University of Montreal|