Bortezomib, Melphalan, and Total-Body Irradiation Before Stem Cell Transplant in Treating Patients With Multiple Myeloma
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|ClinicalTrials.gov Identifier: NCT01936090|
Recruitment Status : Active, not recruiting
First Posted : September 5, 2013
Last Update Posted : April 19, 2018
|Condition or disease||Intervention/treatment||Phase|
|DS Stage I Plasma Cell Myeloma DS Stage II Plasma Cell Myeloma DS Stage III Plasma Cell Myeloma Refractory Plasma Cell Myeloma||Drug: Bortezomib Radiation: Total-Body Irradiation Drug: Melphalan Procedure: Autologous Bone Marrow Transplantation Procedure: Autologous Hematopoietic Stem Cell Transplantation Procedure: Peripheral Blood Stem Cell Transplantation Other: Laboratory Biomarker Analysis||Phase 1|
I. To determine the maximum tolerated dose (MTD) of bortezomib that can be added to high dose melphalan and low dose total body irradiation as part of conditioning chemotherapy for myeloma. (Phase I) II. To determine the efficacy of the bortezomib added to high dose melphalan and low dose total-body irradiation (TBI) in patients with myeloma undergoing stem cell transplantation, as defined by achievement of complete response (CR). (Phase II)
I. To examine the toxicities associated with addition of bortezomib to high dose melphalan and TBI in patients with multiple myeloma (MM).
II. To determine the progression free rate at 1 and 2 years.
I. To determine the proportion of patients achieving a minimal residual disease (MRD) negative status.
II. To assess the HevyLite assay prior to and during treatment.
OUTLINE: This is a phase I, dose-escalation study of bortezomib followed by a phase II study.
CONDITIONING REGIMEN: Patients receive bortezomib intravenously (IV) on days -5 and -2, TBI twice daily (BID) on days -5 and -2, and melphalan IV over 1 hour on days -4 and -3.
TRANSPLANT: Patients undergo autologous bone marrow or peripheral blood stem cell transplant on day 0.
After completion of study treatment, patients are followed up at 100 days and then every 90 days for up to 3 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||11 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Bortezomib, Melphalan and Low Dose TBI Conditioning for Patients Undergoing Autologous Stem Cell Transplantation for Multiple Myeloma|
|Actual Study Start Date :||August 2013|
|Actual Primary Completion Date :||February 2, 2016|
|Estimated Study Completion Date :||October 2018|
U.S. FDA Resources
Experimental: Treatment (bortezomib, TBI, melphalan, stem cell transplant)
Conditioning regimen: Patients receive bortezomib IV on days -5 and -2, TBI BID on days -5 and -2, and melphalan IV over 1 hour on days -4 and -3.
Transplant: Patients undergo autologous bone marrow or peripheral blood stem cell transplant on day 0.
Given IVRadiation: Total-Body Irradiation
Other Names:Drug: Melphalan
Other Name: AlkeranProcedure: Autologous Bone Marrow Transplantation
Undergo autologous bone marrow transplant
Other Names:Procedure: Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous peripheral blood stem cell transplant
Other Name: Autologous Stem Cell TransplantationProcedure: Peripheral Blood Stem Cell Transplantation
Undergo autologous peripheral blood stem cell transplant
Other Names:Other: Laboratory Biomarker Analysis
- MTD defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (phase I) [ Time Frame: Day 36 ]
- The number and severity of all adverse events (phase I) [ Time Frame: Up to 3 years ]Will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion.
- Proportion of complete responses (CR) defined as a CR noted as the objective status on two consecutive evaluations (phase II) [ Time Frame: Up to 3 years ]Will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion. 95% confidence intervals for the true success proportion will be calculated.
- CR rate at day 100 estimated by the total number of patients who achieve a complete CR by day 100 post-transplant divided by the total number of evaluable patients [ Time Frame: At day 100 ]Exact binomial 95% confidence intervals for the true CR rate at day 100 will be calculated.
- Time to progression [ Time Frame: Time from registration to the earliest date with documentation of disease progression, assessed at 1 year ]Will be estimated using the method of Kaplan-Meier.
- Time to progression [ Time Frame: Time from registration to the earliest date with documentation of disease progression, assessed at 2 years ]Will be estimated using the method of Kaplan-Meier.
- Maximum grade for each type of adverse event [ Time Frame: Up to 3 years ]Will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.
- Proportion of patients who achieve MRD negative status estimated by the number of patients who are MRD negative divided by the total number of evaluable patients who achieve a CR [ Time Frame: Up to 3 years ]Exact binomial 95% confidence intervals for the true MRD negative rate will be calculated.
- Abnormal ratio and suppressed uninvolved immunoglobulin assessed by HevyLite assay [ Time Frame: Up to 3 years ]The correlation of these categories with whether MRD is present (yes vs. no) will be evaluated using Fisher's exact test. In addition, the relationship between these categories and time to progression will be evaluated using Kaplan-Meier methods and log-rank statistics.
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): NCT01936090
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Shaji Kumar||Mayo Clinic|