Back to resultsMGTA-145 + Plerixafor in the Mobilization of Hematopoietic Stem Cells for Autologous Transplantation in Multiple Myeloma
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
MGTA-145
Plerixafor
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of multiple myeloma (MM) per the International Myeloma Working Group (IMWG) criteria
- Eligible for autologous stem cell transplantation (ASCT) per institutional guidelines
- Within 1 year of start of therapy for multiple myeloma
- 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 (ANC) > 1500 x 10e6/L
- Platelet count > 100,000 x 10e6/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.
- Total bilirubin > 1.5x upper limit of normal (ULN) in the absence of a documented history of Gilbert's syndrome
- 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, ie, > 6 cycles of 28 days or > 8cycles of 21 days
- Pregnant or lactating
Sites / Locations
- Stanford University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
MGTA-145 and Plerixafor HSC Mobilization
Arm Description
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.
Outcomes
Primary Outcome Measures
Number of Participants For Whom 2.0 x 10e6 CD34+ HSC Cells/kg Could be Collected in 1 or 2 Apheresis Harvests
The study Primary Objective is to assess the efficacy of hematopoietic stem cells (HSC) mobilization with MGTA-145 in combination with plerixafor in patients with multiple myeloma (MM) in preparation for autologous stem cell transplantation (ASCT). The primary outcome was assessed as the number of participants for whom 2.0 x 10e6 CD34+ HSC cells/kg could be collected in 1 or 2 apheresis harvests, after mobilization with MGTA-145 and Plerixafor. The outcome is reported as the number of participants who achieved this level of HSC cells, a number without dispersion.
Secondary Outcome Measures
Other Measures of Hematopoietic Stem Cell (HSC) Yield in the Apheresis Product
The study Primary Objective is to assess the efficacy of hematopoietic stem cells (HSC) mobilization with MGTA-145 in combination with plerixafor in patients with multiple myeloma (MM) in preparation for autologous stem cell transplantation (ASCT). Other secondary outcomes were assessed as the number of participants for whom 2.0 or 4.0 x 10e6 CD34+ HSC cells/kg could be collected in the Day 1 apheresis harvest only, and for whom the total yield ≥ 4.0 or ≥ 6.0 x 106 CD34+ cells/kg. The outcome is reported as the number of participants who achieved these levels of HSC cells, a number without dispersion.
Time To Neutrophil Engraftment
Neutrophil engraftment after hematopoietic stem cells (HSC) transplant (infusion) is an important measure of the medical benefit of the mobilization and hematopoietic stem cells (HSC) infusion procedure. Time to neutrophil engraftment is defined as the number of days from the day of stem cell infusion to the 1st day of 3 consecutive days that absolute neutrophil count (ANC) is ≥ 0.5 x 10e9/L. Only the participants that proceeded to the HSC infusion are included in this outcome, with the outcome is expressed as the median number of days with full range.
Maintenance of Neutrophil Engraftment [Absolute Neutrophil Count (ANC) ≥ 0.5 x 10e9/L]
Maintenance of successful engraftment after initial engraftment is an important assessment of the value of the mobilization and hematopoietic stem cells (HSC) infusion procedure. For participants with successful neutrophil engraftment [absolute neutrophil count (ANC) ≥ 0.5 x 10e9/L], the outcome is reported as the number of participants that had maintained successful graft status [absolute neutrophil count (ANC) ≥ 0.5 x 10e9/L] at 30 days and 100 days after the infusion. The outcome is a number without dispersion.
Time To Platelet Engraftment ≥ 20 x 10e9/L
Platelet engraftment after hematopoietic stem cells (HSC) transplant (infusion) is an important measure of the medical benefit of the mobilization and hematopoietic stem cells (HSC) infusion procedure. Time to platelet engraftment ≥ 20 x 10e9/L is defined as the 1st day of 2 consecutive days that platelet count is ≥ 20 x 10e9/L, without transfusion in the prior 7 days. Only the participants that proceeded to the HSC infusion are included in this outcome, with the outcome is expressed as the median number of days with full range.
Time To Platelet Engraftment ≥ 50 x 10e9/L
Platelet engraftment after hematopoietic stem cells (HSC) transplant (infusion) is an important measure of the medical benefit of the mobilization and hematopoietic stem cells (HSC) infusion procedure. Time to platelet engraftment ≥ 50 x 10e9/L s defined as the 1st day that platelet count is ≥ 50 x 10e9/L, without transfusion in the prior 48 hours. Only the participants that proceeded to the HSC infusion are included in this outcome, with the outcome is expressed as the median number of days, with full range.
Infusion-related Toxicities
Infusion-related toxicities are adverse events considered at least possibly-related to the study treatments MGTA-145, assessed from Baseline to 7 days after mobilization. The outcome is reported as a listing of the preferred terms for the "at least possibly-related" adverse events, with outcome being the number of adverse events of that preferred term. The outcome is a listing of numbers without dispersion.
Progression-free Survival (PFS)
Progression-free survival (PFS) is an important assessment of the value of the mobilization and hematopoietic stem cells (HSC) infusion procedure. For participants that received the HSC infusion, the outcome is reported as the number of participants who remained alive and were without tumor progression, at 100 days after the infusion. The outcome is a number without dispersion.
Transplant-related Mortality
Transplant-related mortality is an important assessment of the value of the mobilization and hematopoietic stem cells (HSC) infusion procedure. For participants that received the HSC infusion, the outcome is reported as the number of participants who had expired for any reason considered at least possibly related to the transplant / infusion procedure, within 100 days of the infusion. The outcome is a number without dispersion.
Non-relapse-related Mortality
For participants that received the HSC infusion, the outcome is reported as the number of participants who had expired for any reason except disease relapse/progression, within 100 days of the infusion. The outcome is a number without dispersion.
Overall Survival (OS)
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.
Overall survival (OS) is an important assessment of the value of the mobilization and hematopoietic stem cells (HSC) infusion procedure. For participants that received the HSC infusion, the outcome is reported as the number of participants who remained alive at 100 days after the infusion. The outcome is a number without dispersion.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04552743
Brief Title
MGTA-145 + Plerixafor in the Mobilization of Hematopoietic Stem Cells for Autologous Transplantation in Multiple Myeloma
Official Title
Phase II Study of MGTA-145 in Combination With Plerixafor in the Mobilization of Hematopoietic Stem Cells for Autologous Transplantation in Patients With Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
October 5, 2020 (Actual)
Primary Completion Date
July 22, 2021 (Actual)
Study Completion Date
June 30, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Surbhi Sidana, MD
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study evaluates a new drug MGTA-145 in combination with plerixafor (Mozobil) to mobilize stem cells into the peripheral blood for collection by apheresis. The stem cells will be used for autologous stem cell transplant for treatment of multiple myeloma.
Detailed Description
PRIMARY OBJECTIVE
1. To assess the efficacy of MGTA-145 in combination with plerixafor in mobilizing adequate number of hematopoietic stem cells (> 2 x 10e6 CD34+ cells/kg) in patients with multiple myeloma (MM) in preparation for autologous stem cell transplantation (ASCT).
SECONDARY OBJECTIVES
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MGTA-145 and Plerixafor HSC Mobilization
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
MGTA-145
Other Intervention Name(s)
GRO beta
Intervention Description
A chemokine receptor type 2 (CXCR2) agonist protein, administered via intravenous (IV) infusion over 3 to 10 minutes.
Intervention Type
Drug
Intervention Name(s)
Plerixafor
Other Intervention Name(s)
Mozobil, AMD 3100, LM-3100
Intervention Description
An azamacrocycle CXCR4 chemokine receptor antagonist, administered at 0.24 mg/kg subcutaneously, reduced to 0.16 mg/kg in patients with renal dysfunction (per package insert).
Primary Outcome Measure Information:
Title
Number of Participants For Whom 2.0 x 10e6 CD34+ HSC Cells/kg Could be Collected in 1 or 2 Apheresis Harvests
Description
The study Primary Objective is to assess the efficacy of hematopoietic stem cells (HSC) mobilization with MGTA-145 in combination with plerixafor in patients with multiple myeloma (MM) in preparation for autologous stem cell transplantation (ASCT). The primary outcome was assessed as the number of participants for whom 2.0 x 10e6 CD34+ HSC cells/kg could be collected in 1 or 2 apheresis harvests, after mobilization with MGTA-145 and Plerixafor. The outcome is reported as the number of participants who achieved this level of HSC cells, a number without dispersion.
Time Frame
2 days
Secondary Outcome Measure Information:
Title
Other Measures of Hematopoietic Stem Cell (HSC) Yield in the Apheresis Product
Description
The study Primary Objective is to assess the efficacy of hematopoietic stem cells (HSC) mobilization with MGTA-145 in combination with plerixafor in patients with multiple myeloma (MM) in preparation for autologous stem cell transplantation (ASCT). Other secondary outcomes were assessed as the number of participants for whom 2.0 or 4.0 x 10e6 CD34+ HSC cells/kg could be collected in the Day 1 apheresis harvest only, and for whom the total yield ≥ 4.0 or ≥ 6.0 x 106 CD34+ cells/kg. The outcome is reported as the number of participants who achieved these levels of HSC cells, a number without dispersion.
Time Frame
2 days
Title
Time To Neutrophil Engraftment
Description
Neutrophil engraftment after hematopoietic stem cells (HSC) transplant (infusion) is an important measure of the medical benefit of the mobilization and hematopoietic stem cells (HSC) infusion procedure. Time to neutrophil engraftment is defined as the number of days from the day of stem cell infusion to the 1st day of 3 consecutive days that absolute neutrophil count (ANC) is ≥ 0.5 x 10e9/L. Only the participants that proceeded to the HSC infusion are included in this outcome, with the outcome is expressed as the median number of days with full range.
Time Frame
15 days
Title
Maintenance of Neutrophil Engraftment [Absolute Neutrophil Count (ANC) ≥ 0.5 x 10e9/L]
Description
Maintenance of successful engraftment after initial engraftment is an important assessment of the value of the mobilization and hematopoietic stem cells (HSC) infusion procedure. For participants with successful neutrophil engraftment [absolute neutrophil count (ANC) ≥ 0.5 x 10e9/L], the outcome is reported as the number of participants that had maintained successful graft status [absolute neutrophil count (ANC) ≥ 0.5 x 10e9/L] at 30 days and 100 days after the infusion. The outcome is a number without dispersion.
Time Frame
100 days
Title
Time To Platelet Engraftment ≥ 20 x 10e9/L
Description
Platelet engraftment after hematopoietic stem cells (HSC) transplant (infusion) is an important measure of the medical benefit of the mobilization and hematopoietic stem cells (HSC) infusion procedure. Time to platelet engraftment ≥ 20 x 10e9/L is defined as the 1st day of 2 consecutive days that platelet count is ≥ 20 x 10e9/L, without transfusion in the prior 7 days. Only the participants that proceeded to the HSC infusion are included in this outcome, with the outcome is expressed as the median number of days with full range.
Time Frame
33 days
Title
Time To Platelet Engraftment ≥ 50 x 10e9/L
Description
Platelet engraftment after hematopoietic stem cells (HSC) transplant (infusion) is an important measure of the medical benefit of the mobilization and hematopoietic stem cells (HSC) infusion procedure. Time to platelet engraftment ≥ 50 x 10e9/L s defined as the 1st day that platelet count is ≥ 50 x 10e9/L, without transfusion in the prior 48 hours. Only the participants that proceeded to the HSC infusion are included in this outcome, with the outcome is expressed as the median number of days, with full range.
Time Frame
44 days
Title
Infusion-related Toxicities
Description
Infusion-related toxicities are adverse events considered at least possibly-related to the study treatments MGTA-145, assessed from Baseline to 7 days after mobilization. The outcome is reported as a listing of the preferred terms for the "at least possibly-related" adverse events, with outcome being the number of adverse events of that preferred term. The outcome is a listing of numbers without dispersion.
Time Frame
7 days after mobilization procedure
Title
Progression-free Survival (PFS)
Description
Progression-free survival (PFS) is an important assessment of the value of the mobilization and hematopoietic stem cells (HSC) infusion procedure. For participants that received the HSC infusion, the outcome is reported as the number of participants who remained alive and were without tumor progression, at 100 days after the infusion. The outcome is a number without dispersion.
Time Frame
100 days after infusion procedure
Title
Transplant-related Mortality
Description
Transplant-related mortality is an important assessment of the value of the mobilization and hematopoietic stem cells (HSC) infusion procedure. For participants that received the HSC infusion, the outcome is reported as the number of participants who had expired for any reason considered at least possibly related to the transplant / infusion procedure, within 100 days of the infusion. The outcome is a number without dispersion.
Time Frame
100 days after infusion procedure
Title
Non-relapse-related Mortality
Description
For participants that received the HSC infusion, the outcome is reported as the number of participants who had expired for any reason except disease relapse/progression, within 100 days of the infusion. The outcome is a number without dispersion.
Time Frame
100 days after infusion procedure
Title
Overall Survival (OS)
Description
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.
Overall survival (OS) is an important assessment of the value of the mobilization and hematopoietic stem cells (HSC) infusion procedure. For participants that received the HSC infusion, the outcome is reported as the number of participants who remained alive at 100 days after the infusion. The outcome is a number without dispersion.
Time Frame
100 days after infusion procedure
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of multiple myeloma (MM) per the International Myeloma Working Group (IMWG) criteria
Eligible for autologous stem cell transplantation (ASCT) per institutional guidelines
Within 1 year of start of therapy for multiple myeloma
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 (ANC) > 1500 x 10e6/L
Platelet count > 100,000 x 10e6/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.
Total bilirubin > 1.5x upper limit of normal (ULN) in the absence of a documented history of Gilbert's syndrome
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, ie, > 6 cycles of 28 days or > 8cycles of 21 days
Pregnant or lactating
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Surbhi Sidana, MD
Organizational Affiliation
Stanford Medicine at Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94304
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
MGTA-145 + Plerixafor in the Mobilization of Hematopoietic Stem Cells for Autologous Transplantation in Multiple Myeloma
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