Clinical trial NCT04762875: MGTA-145 + Plerixafor in the Mobilization of HSCs for Allogeneic Transplant in Hematologic Malignancies
Official title: A Phase II Study Evaluating the Safety and Efficacy of MGTA-145 in Combination With Plerixafor for the Mobilization and Transplantation of HLA-Matched Donor Hematopoietic Stem Cells in Recipients With Hematological Malignancies
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Related Donors Donating PBSC to a Family Member
Healthy Donors
Acute Myelogenous Leukemia
Acute Lymphoblastic Leukemia
Myelodysplastic Syndrome
Lead sponsor: Ensoma
Sponsor class: INDUSTRY
Collaborators: name: National Marrow Donor Program
First posted: 2021-02-21
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 Exclusion Criteria:

* Donor unwilling or unable to give informed consent, or unable to comply with the protocol including required follow-up and testing
* Donor already enrolled on another investigational agent study
* Pregnant or breastfeeding females, sexually active female and male donors not willing or able to use adequate contraception, or males who do not agree to refrain from donating sperm, from the time of consent through 3 months after treatment with MGTA-145 + plerixafor

Recipient Exclusion Criteria:

* Subject unwilling or unable to give informed consent, or unable to comply with the protocol including required follow-up and testing
* Subject whose donor does not meet the eligibility criteria and is a screen fail
* Subjects with a prior allogeneic transplant
* Subjects with active, uncontrolled infection at the time of the transplant preparative regimen
* Pregnant or breastfeeding females, sexually active female or male subjects not willing or able to use adequate contraception, or males who do not agree to refrain from donating sperm, from the time of consent through 3 months after PBSC infusion
* Subjects with clinical evidence of active Central Nervous System (CNS) tumor involvement as evidenced by documented disease on examination of spinal fluid or MRI within 45 days of start of conditioning
* A condition, which, in the opinion of the clinical investigator, would interfere with the evaluation of primary and secondary endpoints
* Planned treatment with a new investigational agent from the time of transplant through 30 days post-transplant

Primary outcomes:
measure: HSC Yield in Apheresis Product
timeFrame: Up to 2 days
Secondary outcomes:
measure: HSC Yield in Apheresis Product
timeFrame: Up to 2 days
measure: Adverse Events Experienced by Donors
timeFrame: Baseline though day 180
measure: Graft Durability
timeFrame: Day 28
measure: Graft-versus Host Disease (GVHD)
timeFrame: Day 100
measure: Treatment-related Mortality
timeFrame: Day 100
measure: Overall Survival
timeFrame: Day 100
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Stanford
country: United States
facility: Stanford Health Care
state: California
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Columbus
country: United States
facility: Ohio State Medical Center, James Cancer Center
state: Ohio
city: Houston
country: United States
facility: M.D. Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Be The Match Collection Center Seattle
state: Washington
Study officials:
affiliation: National Marrow Donor Program
name: Steven Devine, MD
role: STUDY_CHAIR
References: