Acute Lymphoblastic Leukemia, Acute Myelogenous Leukemia, Healthy Donors, Myelodysplastic Syndrome, Related Donors Donating PBSC to a Family Member
Conditions
Brief summary
This research study tests a new medicine for mobilizing stem cells so they can be collected and used for allogeneic stem cell transplant for treatment of hematological malignancies. MGTA-145, the new medicine, will be given with plerixafor.
Detailed description
This is a Phase II, open-label, multicenter, prospective study of MGTA-145 + plerixafor mobilized HLA-matched sibling and matched unrelated donor allografts for myeloablative hematopoietic stem cell transplantation (HSCT) in recipients with hematological malignancies. Donors will undergo 1 or 2 days of mobilization and apheresis.
Interventions
BIOLOGICALMGTA-145
MGTA-145 will be be administered as an IV infusion
BIOLOGICALPlerixafor
240 µg/kg subcutaneously
Sponsors
National Marrow Donor Program
Ensoma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Donor Inclusion Criteria: * Donor medical suitability and eligibility will be determined following Institution or NMDP/Be The Match standards * Age 18-65 years old at the time of signing informed consent * 8/8 (HLA- A, B, C, and DRB1) HLA-matched sibling or volunteer unrelated donor * Fulfill Institution or NMDP/Be The Match criteria to serve as a mobilized blood cell donor * Serum creatinine \< 1.5 x institution upper limit of normal (ULN) or estimated creatinine clearance (CRCL) \> 50 mL/min using the Modification of Diet in Renal Disease Study (MDRD) equation or similar method Recipient Inclusion Criteria: * At least 18 years old at the time of signing informed consent * Has an available 8/8 (HLA- A, B, C, and DRB1) HLA-matched sibling or volunteer unrelated donor willing to donate peripheral blood stem cells (PBSC) for transplant * Fulfill additional individual Transplant Center Criteria for transplant beyond NMDP/Be The Match criteria * One of the following diagnoses: * Acute myelogenous leukemia (AML) in 1st remission or beyond with ≤ 5% marrow blasts and no circulating blasts. Documentation of bone marrow assessment will be accepted within 45 days prior to the date of consent. * Acute lymphoblastic leukemia (ALL) in 1st remission or beyond with ≤ 5% marrow blasts and no circulating blasts. Documentation of bone marrow assessment will be accepted within 45 days prior to the date of consent. * Patients with myelodysplasia (MDS) with no circulating blasts and with less than 10% blasts in the bone marrow (higher blast percentage allowed in MDS due to lack of differences in outcomes with \< 5% or 5-10% blasts in MDS). Documentation of bone marrow assessment will be accepted within 45 days prior to the date of consent. * Cardiac function: Left ventricular ejection fraction at least 45% based on most recent echocardiogram or MUGA results obtained via standard of care * Estimated creatinine clearance acceptable per local institutional guidelines * Pulmonary function: diffusing capacity of the lungs for carbon monoxide (DLCO) corrected for hemoglobin at least 50% and forced expiratory volume in first second (FEV1) predicted at least 50% based on most recent DLCO results obtained via standard of care * Liver function acceptable per local institutional guidelines * Karnofsky performance status (KPS) of 70% or greater * Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) score of 4 or less
Exclusion criteria
Donor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HSC Yield in Apheresis Product | Up to 2 days | Number of subjects with adequate number of hematopoietic stem cells (≥ 2.0 x 10\^6 CD34+ cells/kg) in one apheresis setting. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Day 100 | To determine the probability of overall survival after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor |
| HSC Yield in Apheresis Product | Up to 2 days | To determine the proportion of donors whose cells can be successfully mobilized and collected with a target CD34+ cell dose of at least 4.0 x 10\^6 CD34+ cells/kg actual recipient weight in one apheresis collection |
| Treatment-related Mortality | Day 100 | To determine the proportion of treatment-related mortality and disease relapse/progression after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor |
| Graft Durability | Day 28 | The proportion of participants with primary and secondary graft failure after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor |
| Graft-versus Host Disease (GVHD) | Day 100 | To determine the incidence of acute and chronic graft versus host disease (GVHD) after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor |
| Adverse Events Experienced by Donors | Baseline though day 180 | To ascertain the incidence of adverse events (AEs) before and during apheresis experienced by donors receiving MGTA-145 + plerixafor |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single Dose MGTA-145 Plus Plerixafor Followed by Apheresis MGTA-145 in combination with plerixafor followed by apheresis on one or two consecutive days
MGTA-145: MGTA-145 will be be administered as an IV infusion
Plerixafor: 240 µg/kg subcutaneously | 4 |
| Subjects Transplanted With Plerixafor + MGTA-145 Mobilized Product Transplant recipient after donors mobilized with single-dose MGTA-145 plus plerixafor | 3 |
| Total | 7 |
Baseline characteristics
| Characteristic | Single Dose MGTA-145 Plus Plerixafor Followed by Apheresis | Total | Subjects Transplanted With Plerixafor + MGTA-145 Mobilized Product |
|---|---|---|---|
| Age, Continuous | 44 years | 45 years | 61 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 7 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 3 Participants |
| Weight | 73.7 kg | 77 kg | 81 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 1 / 3 |
| other Total, other adverse events | 4 / 4 | 1 / 3 |
| serious Total, serious adverse events | 0 / 4 | 2 / 3 |
Outcome results
Primary
HSC Yield in Apheresis Product
Number of subjects with adequate number of hematopoietic stem cells (≥ 2.0 x 10\^6 CD34+ cells/kg) in one apheresis setting.
Time frame: Up to 2 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Dose MGTA-145 Plus Plerixafor Followed by Apheresis | HSC Yield in Apheresis Product | 2 Participants |
Secondary
Adverse Events Experienced by Donors
To ascertain the incidence of adverse events (AEs) before and during apheresis experienced by donors receiving MGTA-145 + plerixafor
Time frame: Baseline though day 180
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Dose MGTA-145 Plus Plerixafor Followed by Apheresis | Adverse Events Experienced by Donors | 4 Participants |
Secondary
Graft Durability
The proportion of participants with primary and secondary graft failure after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor
Time frame: Day 28
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Dose MGTA-145 Plus Plerixafor Followed by Apheresis | Graft Durability | 0 Participants |
Secondary
Graft-versus Host Disease (GVHD)
To determine the incidence of acute and chronic graft versus host disease (GVHD) after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor
Time frame: Day 100
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Dose MGTA-145 Plus Plerixafor Followed by Apheresis | Graft-versus Host Disease (GVHD) | 0 Participants |
Secondary
HSC Yield in Apheresis Product
To determine the proportion of donors whose cells can be successfully mobilized and collected with a target CD34+ cell dose of at least 4.0 x 10\^6 CD34+ cells/kg actual recipient weight in one apheresis collection
Time frame: Up to 2 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Dose MGTA-145 Plus Plerixafor Followed by Apheresis | HSC Yield in Apheresis Product | 2 Participants |
Secondary
Overall Survival
To determine the probability of overall survival after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor
Time frame: Day 100
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Dose MGTA-145 Plus Plerixafor Followed by Apheresis | Overall Survival | 2 Participants |
Secondary
Treatment-related Mortality
To determine the proportion of treatment-related mortality and disease relapse/progression after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor
Time frame: Day 100
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Dose MGTA-145 Plus Plerixafor Followed by Apheresis | Treatment-related Mortality | 0 Participants |