MGTA-145 + Plerixafor in the Mobilization of Hematopoietic Stem Cells for Autologous Transplantation in Multiple Myeloma
Study Details
Study Description
Brief Summary
This research study tests a new medicine for mobilizing stem cells so they can be collected and used for autologous stem cell transplant for treatment of multiple myeloma. MGTA-145, the new medicine, will be given with plerixafor.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
PRIMARY OBJECTIVE(S)
-
To assess the efficacy of MGTA-145 in combination with plerixafor in mobilizing adequate number of hematopoietic stem cells (> 2 x 106 CD34+ cells/kg) in patients with multiple myeloma (MM) in preparation for autologous stem cell transplantation (ASCT). SECONDARY OBJECTIVE(S)
-
To assess the efficacy of MGTA-145 and plerixafor in mobilizing different Hematopoietic stem cells (HSCs) target goals in patients with MM in preparation for ASCT.
-
To assess the safety and tolerability of MGTA-145 and plerixafor for mobilizing HSCs in patients with MM.
-
To assess the engraftment rate and time to engraftment following ASCT after HSC mobilization with MGTA-145 and plerixafor in patients with MM undergoing upfront ASCT.
-
To assess rate of ongoing engraftment at day 30 and 100 after stem cell infusion in patients with MM who are mobilized with MGTA-145 and plerixafor undergoing upfront ASCT.
-
To assess transplant and disease-related outcomes after mobilization of HSCs with MGTA- 145 and plerixafor in patients with MM undergoing upfront ASCT.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: MGTA-145 and Plerixafor HSC Mobilization Patients after screening will undergo baseline evaluation during the premobilization phase up to 30 days before mobilization. Patients will undergo sequential administration of plerixafor 0.24 mg/kg subcutaneously followed 2 hours later by MGTA-145 at 0.03 mg/kg intravenously (3 to10 minute infusion). This will be followed by apheresis. A second day of mobilization and apheresis will be pursued in patients who have not collected 6.0 x 106 CD34+ cells/kg in one session. |
Drug: MGTA-145
MGTA-145 investigational agent will be provided by Magenta Therapeutics. MGTA-145 will be administered as an IV infusion over 3 to10 minutes, as clinically indicated.
Drug: Plerixafor
Plerixafor (0.24 mg/kg) will be administered subcutaneously. Plerixafor dose will be reduced to 0.16 mg/kg in patients with renal dysfunction per package insert
Other Names:
|
Outcome Measures
Primary Outcome Measures
- HSC yield in apheresis product [2 days of stem cell mobilization and apheresis]
The primary outcome is collection of 2.0 x 106 CD34 cells/kg in one or two days of apheresis after mobilization with MGTA-145 and plerixafor. CD34 yield of collected HSCs expressed as CD34+ cells/kg of patient body weight.
Secondary Outcome Measures
- Infusion related toxicities with MGTA-145 [7 days after mobilization]
Adverse events will be collected based on NCI CTCAE version 5 with mobilization of HSCs with MGTA-145 and plerixafor.
- Neutrophil engraftment [48 hours]
Only patients proceeding with upfront transplant will be assessed. Time to primary engraftment is defined as time in days from the day of stem cell infusion to the first day of engraftment. Neutrophil engraftment is defined as the first day of Absolute neutrophil count (ANC) ≥0.5 x 109/L for 3 days following stem cell infusion. This is assessed by absolute neutrophil counts obtained as part of complete blood count (CBC) with differential. It is standard practice to follow patients regularly in the inpatient unit/outpatient transplant unit until they achieve engraftment.
- Platelet engraftment [48 hours]
Only patients proceeding with upfront transplant will be assessed. Time to primary engraftment is defined as time in days from the day of stem cell infusion to the first day of engraftment. • Platelet engraftment is defined as the first day of platelet count more than or equal to 20 x 109/L without transfusion in the last 7 days and with platelet count ≥20 x 109/L on 2 separate, subsequent days. This is assessed by platelets counts obtained as part of CBC with differential. It is standard practice to follow patients regularly in the transplant inpatient unit/outpatient transplant until they achieve engraftment.
- Transplant related mortality [100 days]
Only patients proceeding with upfront transplant will be assessed. Transplant related mortality is described as death from any cause within the first 100 days of HSC infusion.
- Non-relapse related mortality [100 days]
Only patients proceeding with upfront transplant will be assessed. Transplant related non-relapse mortality is described as death from any cause except disease relapse/progression within the first 100 days of HSC infusion.
- Progression Free Survival (PFS) [100 days after transplant]
Only patients proceeding with upfront transplant will be assessed. Duration from start of the ASCT to disease progression or death (regardless of cause of death), whichever comes first. Progression will be assessed using day 100 post-transplant response and PFS rates will be reported at day 100 in patients undergoing upfront transplant.
- Overall Survival (OS) [100 days after transplant]
Only patients proceeding with upfront transplant will be assessed. Overall survival is defined as duration from start of the ASCT to death (regardless of cause of death). This will be assessed from start of transplant and OS rates will be reported at day100 following transplant in patients undergoing upfront transplant.
- Response Assessment [100 days]
Response before mobilization will be assessed in all patients. Response/progression following transplant will be assessed in patients undergoing upfront transplant. Myeloma response before stem cell mobilization and at day 100 will be assessed per the International Myeloma Working Group Uniform Response Criteria.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Diagnosis of multiple myeloma per the International Myeloma Working Group (IMWG) criteria
-
Eligible for ASCT per institutional guidelines
-
Within one year of start of myeloma therapy
-
Cardiac and pulmonary status sufficient to undergo apheresis and transplantation per institutional transplant guidelines.
-
Calculated creatinine clearance > 30 mL/min according to the Modification of Diet in Renal Disease (MDRD) formula.
-
Absolute neutrophil count > 1500 x106/L and platelets > 100,000 x106/L
-
Ability to understand and the willingness to sign a written informed consent document.
-
Agreement to use an approved form of contraception for male patients or female patients of childbearing potential.
Exclusion Criteria:
-
History of prior stem cell transplant for multiple myeloma or other indications
-
Planned tandem stem cell transplant
-
Prior history of failure to collect HSCs.
-
Liver function tests: Total bilirubin >1.5x upper limit of normal (ULN) in the absence of a documented history of Gilbert's syndrome and/or aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 3x ULN.
-
Known allergy to MGTA-145 or plerixafor.
-
Lifetime exposure to lenalidomide or another immunomodulatory drug greater than 6 cumulative months of treatment i.e more than six 28-day cycles or more than eight 21-day cycles.
-
Pregnant or lactating women.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Stanford University | Stanford | California | United States | 94304 |
Sponsors and Collaborators
- Stanford University
Investigators
- Principal Investigator: Surbhi Sidana, MD, Stanford University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IRB-57056
- BMT362