Feasibility and Safety of Collecting and Combining Autologous Hematopoietic Stem Cells with Chimeric Antigen Receptor (CAR) T-Cell Therapy in Subjects with Relapsed/Refractory Hematological Malignancies

Trial Title: Feasibility and Safety of Collecting and Combining Autologous Hematopoietic Stem Cells with Chimeric Antigen Receptor (CAR) T-Cell Therapy in Subjects with Relapsed/Refractory Hematological Malignancies

NCT ID: NCT05887167

Condition: Hematologic Malignancy
Large B-cell Lymphoma
Acute Lymphoblastic Leukemia
Mantle Cell Lymphoma
Multiple Myeloma
Diffuse Large B Cell Lymphoma

Conditions: Official terms:
Lymphoma
Multiple Myeloma
Neoplasms
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Hematologic Neoplasms

Conditions: Keywords:
CAR T-cell therapy
autologous hematopoietic stem cells
CAR T
CAR T therapy

Study type: Interventional

Study phase: Phase 1

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Biological
Intervention name: autologous hematopoietic stem cells added to planned CAR T
Description: Autologous hematopoietic stem cells (aHSCs) infused on Day 10 after CAR T (any FDA-approved CAR T product) infusion on Day 0.
Arm group label: CAR T Therapy with Autologous Hematopoietic Stem Cells (aHSCs)

Summary: The study is designed to examine the feasibility and safety of collecting autologous hematopoietic stem cells (HSCs) to be combined with CAR T-cell therapy for patients with relapsed/refractory (r/r) hematological disease. The study will evaluate feasibility of collecting the target dose of HSCs from at least 50% of enrolled patients. The study will assess safety based on incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in the first 60 days post CAR T dosing, and also through the collection of adverse events (AEs) and serious adverse events (SAEs) as well as the durability of response after treatment with HSCs with CAR T. The study follows an open-label, single-center and single non-randomized cohort design. 20 subjects with r/r hematological malignancies will be enrolled and treated to evaluate the feasibility and preliminary safety of collecting autologous HSCs and combining them with CAR T-cell therapy.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Age 18 - 85 years. - Histologically proven hematological malignancy according to the World Health Organization 2016 classification criteria for which a commercially available, FDA-approved CAR T product exists. - Relapsed or refractory disease, defined by the following: - Disease progression after last regimen, or - Refractory disease: failure to achieve a partial response (PR) or complete remission (CR) to the last regimen - At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy for the malignancy at the time the subject is planned for leukapheresis. - Toxicities due to prior therapy must be stable or recovered to ≤ Grade 1 with the exception of alopecia. - Subjects with an active uncontrolled infection should not start CAR T treatment until the infection has resolved. - Eastern cooperative oncology group (ECOG) performance status 0 - 2. - Adequate hematologic, hepatic, and cardiac function - Serum pregnancy test for women of childbearing potential (WOCBP) at Screening. - Willing to comply to research specimen collection as specified in the protocol. - Written informed consent obtained from subject and ability for subject to comply with the requirements of the study. Exclusion Criteria: - Autologous hematopoietic cell transplant intent or execution within 8 weeks of planned CAR T infusion. - History of allogeneic cell transplantation within 8 weeks of planned CAR T infusion. - Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management at time of screening. - History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 6 months of enrollment. - History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, or any autoimmune disease with CNS involvement. - Doses of corticosteroids of greater than or equal to 5 mg/day of prednisone or equivalent doses of other corticosteroids and other immunosuppressive drugs are not allowed prior to enrollment. A washout period of 10 days prior to leukapheresis and 10 days prior to anti-CD19 CAR T cell administration is required. - Any medical condition likely to interfere with assessment of feasibility or safety of study treatment. - Live vaccine ≤ 6 weeks prior to planned start of conditioning regimen. - History of severe immediate hypersensitivity reaction to any of the agents used in this study. - Current pregnancy or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. - Subjects of both sexes who are not willing to practice birth control from the time of consent through 6 months after the completion of conditioning chemotherapy. Females who have undergone surgical sterilization or who have been postmenopausal for at least 1 year are not considered to be of childbearing potential. - In the investigator's judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation. - Patients with obvious myeloid clonal hematopoiesis on the screening bone marrow biopsy will be excluded based on the risk of developing myeloid neoplasms with aHSC infusion.

Gender: All

Minimum age: 18 Years

Maximum age: 85 Years

Healthy volunteers: No

Locations:

Facility:
Name: Cedars-Sinai Medical Center

Address:
City: Los Angeles
Zip: 90048
Country: United States

Status: Recruiting

Contact:
Last name: Clinical Trial Recruitment Navigator

Phone: 310-423-2133
Email: cancer.trial.info@cshs.org

Contact backup:
Last name: John Chute, MD

Contact backup:
Last name: Justin Darrah, MD

Contact backup:
Last name: Noah Merin, MD, PhD

Contact backup:
Last name: Ronald Paquette, MD

Contact backup:
Last name: Robert Vescio, MD

Contact backup:
Last name: Hannah Lee, MD

Contact backup:
Last name: Akil Merchant, MD

Contact backup:
Last name: David Oveisi, MD

Contact backup:
Last name: Leslie Ballas, MD

Start date: March 2, 2024

Completion date: December 15, 2026

Lead sponsor:
Agency: Joshua Sasine, MD, PhD
Agency class: Other

Source: Cedars-Sinai Medical Center

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05887167