Study of ProTmune for Allogeneic HCT in Adult Patients With Hematologic Malignancies

Study Overview
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Brief Summary
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This study is a Phase 1, non-randomized, open-label/Phase 2 randomized, blinded study of ProTmune (ex vivo programmed mobilized peripheral blood cells) versus non-programmed mobilized peripheral blood cells for allogeneic hematopoietic cell transplantation (HCT) in adult subjects aged 18 years and older with hematologic malignancies. A total of 88 study subjects were treated in the trial at approximately 15 centers in the US.

Official Title
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A Phase 1, Non-Randomized, Open-Label/Phase 2, Randomized, Blinded Study of ProTmune™ (ex Vivo Programmed Mobilized Peripheral Blood Cells) Versus Non-Programmed Mobilized Peripheral Blood Cells for Allogeneic Hematopoietic Cell Transplantation in Adult Subjects With Hematologic Malignancies

Conditions
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Hematologic Malignancies, Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndromes, Chronic Myelogenous Leukemia, Acute Graft-versus-host Disease

Intervention / Treatment
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* Biological: ProTmune
* Biological: Control Arm


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male and female patients aged 18 years and older, inclusive; Patients must have a hematologic malignancy for which allogeneic hematopoietic peripheral blood cell transplantation is deemed clinically appropriate. Eligible diseases and stages include the following: Acute myeloid leukemia Acute lymphoblastic leukemia, including T lymphoblastic lymphoma with a history of marrow involvement Myelodysplastic Syndrome Chronic myelogenous leukemia Availability of a suitable 8/8 HLA-A, -B, -C, and -DRB1-matched unrelated mPB donor; mBP donor collection that meets protocol specifications; Adequate performance status, defined as Karnofsky score greater than or equal to 70%; For female patients of childbearing potential, all of the following criteria must be met: They are not pregnant (i.e., female patients must have a negative serum pregnancy test at screening); They are not breastfeeding; They do not plan to become pregnant during the study; and They are using an effective method of contraception from screening to the end of the study, unless their sexual partner is surgically sterile. For male patients, agreement to use condoms with spermicide during sexual intercourse from screening to the end of study; and Willingness and ability to sign an IRB/IEC-approved ICF before performance of any study-specific procedures or tests and to comply with protocol visits, and study procedures. Key Exclusion Criteria: Phase 1 only: Known bone marrow fibrosis; Phase 2 only: Bone marrow fibrosis grade 3 (severe) or greater; Positive serology for human immunodeficiency virus (HIV) or human T-cell lymphotropic virus (HTLV) at any time prior to enrollment; Currently uncontrolled bacterial, viral, or fungal infection (progression of clinical symptoms despite therapy); Prior autologous or allogeneic HCT; Active malignancy, other than the one for which the allogeneic mPB transplant is being performed, within 12 months of enrollment, excluding superficial basal cell and carcinoma in situ cervical cancer; Pulmonary disease, renal dysfunction, hepatic disease, cardiac disease, neurologic disease; Participation in another clinical trial involving an investigational product within 30 days prior to screening; or Any condition or therapy, which, in the opinion of the Investigator, might pose a risk to the patient or make participation in the study not in the best interest of the patient.

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ProTmune<br>Conditioning regimen consisting of one of the following five preparative regimens: fludarabine and busulfan (FluBu4); busulfan (Bu) and cyclophosphamide (Cy); Cy and >or=12 Gy total body irradiation (TBI); TBI and etoposide; or fludarabine and melphalan (FluMel 140). Subjects will receive mPB cells from an available 8/8 HLA-A, -B, -C, and -DRB1-matched unrelated peripheral blood cell donor that were programmed ex vivo with ProTmune. | Biological: ProTmune<br>* Ex-vivo, programmed mobilized peripheral blood (mPB) cells<br>|
| Active Comparator: Control Arm<br>Conditioning regimen consisting of one of the following five preparative regimens: fludarabine and busulfan (FluBu4); busulfan (Bu) and cyclophosphamide (Cy); Cy and >or=12 Gy total body irradiation (TBI); TBI and etoposide; or fludarabine and melphalan (FluMel 140). Subjects will receive unmanipulated mPB cells from an available 8/8 HLA-A, -B, -C, and -DRB1-matched unrelated peripheral blood cell donor. | Biological: Control Arm<br>* Untreated mobilized peripheral blood (mPB) cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Cumulative Incidence of Grade II to IV aGvHD Through Day +100 Based on Investigator Assessment | Acute GvHD (aGvHD) is assessed by assigning the clinical stage for the target organs (skin, liver, and gut) along with assigning an overall grade based on the minimum degree of organ involvement required to confer that grade. Grade II is defined as Stage 1 skin, Stage 1 liver, or Stage 1 GI; Grade III is defined as any Stage 1-3 skin, and Stage 2-3 liver, or Stage 2-4 GI; Grade IV is defined as Stage 4 skin, or Stage 4 liver and any Stage GI. A higher overall grade indicates a more severe outcome. The cumulative incidence of CIBMTR Grade II to IV aGVHD through approximately 100 days following HCT is measured by the percentage of participants who experienced grade II to IV aGVHD. The cumulative incidence and the associated 95% confidence interval are estimated using a competing risk analysis with death and relapse without grade II-IV aGvHD as a competing risk. | 100 days post-HCT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year GvHD-free, Relapse-free Survival (GRFS) | 1-year GvHD-free, relapse-free survival (GRFS) is a composite endpoint in which events included Grade III to IV aGvHD, cGvHD requiring systemic immunosuppressive therapy, relapse, or death from any cause. GRFS is defined as the time from HCT to the earlier of the dates of the first documented CIBMTR Grade III-IV aGvHD, first use of systemic immunosuppressive therapy for cGvHD, first documented relapse of the underlying malignancy, or death from any cause. Subjects who are alive with no documented events for Grade III-IV aGvHD, use of systemic immunosuppressive therapy for cGvHD, relapse, or death at the data cutoff will be censored at their last visit date or follow-up on or prior to the date of one-year study completion/early discontinuation. The Kaplan-Meier estimate of the median GRFS and the 95% CI are presented | 365 days post-HCT | 
| Percentage of Subjects Alive Without Relapse and Without Moderate or Severe cGvHD at Day +365 - mITT Population | Percentage of subjects alive without relapse and without moderate or severe cGvHD per NIH Consensus Criteria at Day +365 | 365 days post-HCT | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MDS, Cell Transplants, Hematopoietic Cell Transplant, HCT, Hematologic Malignancies, Hematologic Malignancy, Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, ALL, AML, Myelodysplastic Syndrome, Allogeneic, CML, Stem Cell Transplant, Transplant, aGvHD, Acute graft-versus-host Disease, cGvHD, Chronic graft-versus-host Disease