Carfilzomib + High Dose Melphalan as Preparative Regimen for Autologous Hematopoietic Stem Cell Transplantation
This study is for patients that have multiple myeloma that has come back or relapsed and their condition indicates a procedure called an Autologous Hematopoietic Stem Cell Transplantation (AHSCT). AHSCT is a procedure when stem cells from bone marrow or blood are removed before high-dose chemotherapy. Afterwards, the removed stem cells are put back into the patient's body to form a new population of blood cells.
The high-dose chemotherapy administered before the AHSCT is called "Conditioning Therapy." The FDA has approved the use of the drug melphalan as a conditioning therapy. This research study will look at whether adding the study drug called carfilzomib will improve participant outcomes. Carfilzomib is considered investigational and is not approved by the FDA for the treatment of relapsed multiple myeloma.
This study is divided into two phases.
Phase I: Dose Escalation Phase:
The main purpose of Part I of this study is to examine the safety of the study drug, carfilzomib, and determine the safest amount of the study drug that can be given to subjects who have multiple myeloma. Subjects on this study will receive different dose levels of the study drug. If you are one of the first three subjects to receive the study drug, it will be at what is called the 'starting dose' for the study which is the lowest dose that is expected to be tolerated based on prior research. After the first set of participants receive the study drug, the study doctor will review their health to see how they are tolerating the treatment. This will decide if the study drug dosage will be increased or decreased for the next set of subjects who join the study. It is anticipated that 12- 18 participants will enroll in the Phase I portion of this study.
Phase II: Safety Confirmation Phase:
Once the study doctor has discovered the highest possible dose of study drug that subjects can tolerate, up to 28 more subjects may be enrolled at that dose level. The main purpose of the Phase II portion of the study is look at how effective the combination of carfilzomib and melphalan when given before your stem cell transplantation is in treating multiple myeloma. This expansion phase will also include evaluation of two single agent carfilzomib maintenance therapy regimens for patients without disease progression at day 100.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase 1/2A Study Carfilzomib + High Dose Melphalan as Preparative Regimen for Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma|
- To determine the Maximum Tolerated Dose (MTD) of carfilzomib plus melphalan as conditioning for AHSCT in patients with relapsed Multiple Myeloma(MM) [Phase I portion of study] [ Time Frame: Up to 4 1/2 months ] [ Designated as safety issue: Yes ]
- Very Good Partial Response (VGPR) Rate. [ Time Frame: Up to 17 months ] [ Designated as safety issue: No ]
VGPR defined as any one of the following:
≥ 90% reduction of serum M-protein; ≥ 90% reduction in 24-hour urinary M-protein or decrease to < 100 mg per 24 hour; ≥ 50% decrease in the difference between involved and uninvolved FLC levels or a 50% decrease in level of involved FLC with 50% decrease in ratio; ≥ 50% reduction in bone marrow plasma cells; ≥ 50% reduction in the size of soft tissue plasmacytomas.
- Complete Response (CR) Rate. [ Time Frame: Up to 17 months ] [ Designated as safety issue: No ]CR defined as the following: Negative immunofixation of the serum and urine. If only the measurable non-bone marrow parameter was FLC, normalization of FLC ratio. < 5% plasma cells in bone marrow. And, disappearance of any soft tissue plasmacytomas.
- Median time for neutrophil and platelet engraftment. [ Time Frame: Up to 1 month. ] [ Designated as safety issue: Yes ]Neutrophil engraftment is defined as the first of three consecutive days with absolute neutrophil count >500/mm3. Platelet engraftment is defined as the first of 3 consecutive days of platelets > 20,000/mm3 without platelet transfusion in the prior 7 days.
- Frequency and nature of grades 3 and 4 non-hematologic adverse events during the transplant component. [ Time Frame: Up to 4 1/2 months ] [ Designated as safety issue: Yes ]Grading of AE's is performed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
- To investigate the pharmacodynamic effects of carfilzomib + high dose melphalan in terms of changes in expression of fanconi anemia/BRCA DNA repair genes and DNA fragmentation [ Time Frame: 4 1/2 months ] [ Designated as safety issue: No ]
|Study Start Date:||May 2012|
|Estimated Study Completion Date:||February 2018|
|Estimated Primary Completion Date:||November 2016 (Final data collection date for primary outcome measure)|
Experimental: Carfilzomib + high dose melphalan
Subjects will receive the appropriate dose of carfilzomib (according to assigned cohort in phase 1 and at the determined MTD in phase 2) on days -3 and -2. Carfilzomib will be infused over 30 minutes. Prophylaxis of chemotherapy induced nausea and vomiting will follow institutional guidelines and SOPs.Drug: Melphalan
Subjects will receive 200 mg/m2 of intravenous melphalan on Day -2. Administered as an intravenous push or a fast infusion according to institutional standard operating procedure (SOP). Prophylaxis of chemotherapy induced nausea and vomiting will follow institutional guidelines and SOPs.
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01690143
|United States, Alabama|
|Birmingham, Alabama, United States, 35294|
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, South Carolina|
|Medical University of South Carolina Hollings Cancer Center|
|Charleston, South Carolina, United States, 29425|
|United States, Wisconsin|
|Medical College of Wisconsin|
|Milwaukee, Wisconsin, United States, 53226|
|Principal Investigator:||Luciano Costa, MD||University of Alabama at Birmingham|