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

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02743351
• Other study ID #: PT-001
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 20, 2016
• Est. completion date: November 5, 2021

Study information

• Verified date: December 2022
• Source: Fate Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: November 5, 2021
• Est. primary completion date: December 4, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

1. Male and female patients aged 18 years and older, inclusive;

2. 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:

1. Acute myeloid leukemia

2. Acute lymphoblastic leukemia, including T lymphoblastic lymphoma with a history of marrow involvement

3. Myelodysplastic Syndrome

4. Chronic myelogenous leukemia

3. Availability of a suitable 8/8 HLA-A, -B, -C, and -DRB1-matched unrelated mPB donor;

4. mBP donor collection that meets protocol specifications;

5. Adequate performance status, defined as Karnofsky score greater than or equal to 70%;

6. 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.

7. For male patients, agreement to use condoms with spermicide during sexual intercourse from screening to the end of study; and

8. 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:

1. Phase 1 only: Known bone marrow fibrosis; Phase 2 only: Bone marrow fibrosis grade 3 (severe) or greater;

2. Positive serology for human immunodeficiency virus (HIV) or human T-cell lymphotropic virus (HTLV) at any time prior to enrollment;

3. Currently uncontrolled bacterial, viral, or fungal infection (progression of clinical symptoms despite therapy);

4. Prior autologous or allogeneic HCT;

5. 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;

6. Pulmonary disease, renal dysfunction, hepatic disease, cardiac disease, neurologic disease;

7. Participation in another clinical trial involving an investigational product within 30 days prior to screening; or

8. 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.

Related Conditions & MeSH terms

• Acute Graft-versus-host Disease
• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Chronic Myelogenous Leukemia
• Graft vs Host Disease
• Hematologic Malignancies
• Hematologic Neoplasms
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Neoplasms
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia

Intervention

Biological:
• ProTmune
Ex-vivo, programmed mobilized peripheral blood (mPB) cells
• Control Arm
Untreated mobilized peripheral blood (mPB) cells

Locations

Country	Name	City	State
United States	University of Alabama	Birmingham	Alabama
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	University of Chicago	Chicago	Illinois
United States	Jewish Hospital	Cincinnati	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Indiana Blood and Marrow Transplant	Indianapolis	Indiana
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Weill Cornell Medicine	New York	New York
United States	Oregon Health & Science University	Portland	Oregon
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Huntsman Cancer Institute (University of Utah)	Salt Lake City	Utah
United States	Texas Transplant Institute	San Antonio	Texas
United States	University of California, San Diego (UCSD) Moores Cancer Center	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Fate Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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