MGTA-145 + Plerixafor in the Mobilization of Hematopoietic Stem Cells for Autologous Transplantation in Multiple Myeloma

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: MGTA-145
* Drug: Plerixafor


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MGTA-145 and Plerixafor HSC Mobilization<br>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<br>* A chemokine receptor type 2 (CXCR2) agonist protein, administered via intravenous (IV) infusion over 3 to 10 minutes.<br>* Other names: GRO beta;Drug: Plerixafor<br>* 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).<br>* Other names: LM-3100;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 2 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 2 days | 
| 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. | 15 days | 
| 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. | 100 days | 
| 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. | 33 days | 
| 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. | 44 days | 
| 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. | 7 days after mobilization procedure | 
| 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. | 100 days after infusion procedure | 
| 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. | 100 days after infusion procedure | 
| 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. | 100 days after infusion procedure | 
| 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. | 100 days after infusion procedure |