Multiple Myeloma
Conditions
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 1. 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. 2. To assess the safety and tolerability of MGTA-145 and plerixafor for mobilizing HSCs in patients with MM. 3. 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. 4. 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. 5. To assess transplant and disease-related outcomes after mobilization of HSCs with MGTA-145 and plerixafor in patients with MM undergoing upfront ASCT.
Interventions
DRUGPlerixafor
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).
DRUGMGTA-145
A chemokine receptor type 2 (CXCR2) agonist protein, administered via intravenous (IV) infusion over 3 to 10 minutes.
Sponsors
Surbhi Sidana, MD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants For Whom 2.0 x 10e6 CD34+ HSC Cells/kg Could be Collected in 1 or 2 Apheresis Harvests | 2 days | 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
| Measure | Time frame | Description |
|---|---|---|
| Time To Neutrophil Engraftment | 15 days | 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] | 100 days | 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 | 33 days | 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 | 44 days | 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. |
| Other Measures of Hematopoietic Stem Cell (HSC) Yield in the Apheresis Product | 2 days | 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. |
| Progression-free Survival (PFS) | 100 days after infusion procedure | 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 | 100 days after infusion procedure | 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 | 100 days after infusion procedure | 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) | 100 days after infusion procedure | 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. |
| Infusion-related Toxicities | 7 days after mobilization procedure | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
MGTA-145: A chemokine receptor type 2 (CXCR2) agonist protein, administered via intravenous (IV) infusion over 3 to 10 minutes.
Plerixafor: 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). | 25 |
| Total | 25 |
Baseline characteristics
| Characteristic | MGTA-145 and Plerixafor HSC Mobilization |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants |
| Age, Continuous | 62.2 years STANDARD_DEVIATION 7.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Region of Enrollment United States | 25 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 25 |
| other Total, other adverse events | 25 / 25 |
| serious Total, serious adverse events | 0 / 25 |
Outcome results
Primary
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.
Time frame: 2 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MGTA-145 and Plerixafor HSC Mobilization | Number of Participants For Whom 2.0 x 10e6 CD34+ HSC Cells/kg Could be Collected in 1 or 2 Apheresis Harvests | 22 Participants |
Secondary
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.
Time frame: 7 days after mobilization procedure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MGTA-145 and Plerixafor HSC Mobilization | Infusion-related Toxicities | Pain | 11 adverse events |
| MGTA-145 and Plerixafor HSC Mobilization | Infusion-related Toxicities | Aspartate/alanine aminotransferase increase | 1 adverse events |
| MGTA-145 and Plerixafor HSC Mobilization | Infusion-related Toxicities | Nausea | 2 adverse events |
| MGTA-145 and Plerixafor HSC Mobilization | Infusion-related Toxicities | Headache | 1 adverse events |
| MGTA-145 and Plerixafor HSC Mobilization | Infusion-related Toxicities | Hyperhidrosis | 1 adverse events |
| MGTA-145 and Plerixafor HSC Mobilization | Infusion-related Toxicities | Low platelet count | 2 adverse events |
| MGTA-145 and Plerixafor HSC Mobilization | Infusion-related Toxicities | Vomiting | 1 adverse events |
| MGTA-145 and Plerixafor HSC Mobilization | Infusion-related Toxicities | Poor Graft Function (beyond 7 days post-mobilization) | 1 adverse events |
Secondary
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 frame: 100 days
Population: This outcome is limited to participants that proceeded to the hematopoietic stem cell (HSC) infusion procedure, and with successful neutrophil engraftment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MGTA-145 and Plerixafor HSC Mobilization | Maintenance of Neutrophil Engraftment [Absolute Neutrophil Count (ANC) ≥ 0.5 x 10e9/L] | ANC ≥ 0.5 x 10e9/L at 30 days | 19 Participants |
| MGTA-145 and Plerixafor HSC Mobilization | Maintenance of Neutrophil Engraftment [Absolute Neutrophil Count (ANC) ≥ 0.5 x 10e9/L] | ANC ≥ 0.5 x 10e9/L at 100 days | 19 Participants |
Secondary
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.
Time frame: 100 days after infusion procedure
Population: This outcome is limited to participants that proceeded to the hematopoietic stem cell (HSC) infusion procedure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MGTA-145 and Plerixafor HSC Mobilization | Non-relapse-related Mortality | 0 Participants |
Secondary
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 frame: 2 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MGTA-145 and Plerixafor HSC Mobilization | Other Measures of Hematopoietic Stem Cell (HSC) Yield in the Apheresis Product | ≥ 2.0 x 10e6 CD34+ cells/kg on Day 1 | 17 Participants |
| MGTA-145 and Plerixafor HSC Mobilization | Other Measures of Hematopoietic Stem Cell (HSC) Yield in the Apheresis Product | ≥ 4.0 x 10e6 CD34+ cells/kg on Day 1 | 9 Participants |
| MGTA-145 and Plerixafor HSC Mobilization | Other Measures of Hematopoietic Stem Cell (HSC) Yield in the Apheresis Product | Total ≥ 4.0 x 10e6 CD34+ cells/kg | 17 Participants |
| MGTA-145 and Plerixafor HSC Mobilization | Other Measures of Hematopoietic Stem Cell (HSC) Yield in the Apheresis Product | Total ≥ 6.0 x 10e6 CD34+ cells/kg | 10 Participants |
Secondary
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.
Time frame: 100 days after infusion procedure
Population: This outcome is limited to participants that proceeded to the hematopoietic stem cell (HSC) infusion procedure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MGTA-145 and Plerixafor HSC Mobilization | Overall Survival (OS) | 19 Participants |
Secondary
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.
Time frame: 100 days after infusion procedure
Population: This outcome is limited to participants that proceeded to the hematopoietic stem cell (HSC) infusion procedure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MGTA-145 and Plerixafor HSC Mobilization | Progression-free Survival (PFS) | 18 Participants |
Secondary
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.
Time frame: 15 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MGTA-145 and Plerixafor HSC Mobilization | Time To Neutrophil Engraftment | 12 days |
Secondary
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 frame: 33 days
Population: This outcome is limited to participants that proceeded to the hematopoietic stem cell (HSC) infusion procedure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MGTA-145 and Plerixafor HSC Mobilization | Time To Platelet Engraftment ≥ 20 x 10e9/L | 18 days |
Secondary
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.
Time frame: 44 days
Population: This outcome is limited to participants that proceeded to the hematopoietic stem cell (HSC) infusion procedure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MGTA-145 and Plerixafor HSC Mobilization | Time To Platelet Engraftment ≥ 50 x 10e9/L | 20 days |
Secondary
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.
Time frame: 100 days after infusion procedure
Population: This outcome is limited to participants that proceeded to the hematopoietic stem cell (HSC) infusion procedure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MGTA-145 and Plerixafor HSC Mobilization | Transplant-related Mortality | 0 Participants |