Phase I/II Study of CD5 CAR Engineered IL15-Transduced Cord Blood-Derived NK Cells in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapsed/Refractory Hematological Malignances

Phase 1

Recruiting

• Conditions: Hematological Malignancy
• Interventions: Drug: Fludarabine Phosphate; Drug: Cyclophosphamide; Drug: CAR.5/IL15-transduced CB-NK cells

• Registration Number: NCT05110742
• Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary

To determine the safety, efficacy and optimal cell dose of CAR 5/IL15-transduced CB-NK cells in patients with relapsed/refractory T-cell malignances, mantle cell lymphoma, and chronic lymphocytic leukemia. The efficacy and optimal dose will be identified for individual diseases.

Detailed Description

Primary objective:

To determine the safety, tolerability and optimal cell dose of iC9/CD5CAR/IL-15 NK cells in patients with relapsed/refractory T-cell malignances, mantle cell lymphoma, and chronic lymphocytic leukemia. The efficacy and optimal dose will be identified for individual diseases.

Secondary Objectives:

* To assess the overall response rate (complete and partial response rates)

* To quantify persistence of infused allogeneic donor iC9/CD5CAR/IL-15 NK cells in the recipient.

* To conduct comprehensive immune reconstitution studies.

Study Timeline

• Study First Submitted: 2021-09-28
• Study First Submitted QC: 2021-10-26
• Study First Posted: 2021-11-08
• Study Start: 2024-04-22
• Status Verified: 2025-05
• Last Update Submitted: 2025-07-21
• Last Update Posted: 2025-07-24
• Primary Completion: 2027-12-30
• Study Completion: 2027-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 2 Dose Level	Fludarabine Phosphate	Patients will be randomized between the 2 optimal doses of CAR.5/IL15-transduced CB-NK cells determined by Phase 1. All patients will receive Lymphodepleting Chemotherapy of Cyclophosphamide and Fludarabine.
Phase 2 Dose Level	CAR.5/IL15-transduced CB-NK cells	Patients will be randomized between the 2 optimal doses of CAR.5/IL15-transduced CB-NK cells determined by Phase 1. All patients will receive Lymphodepleting Chemotherapy of Cyclophosphamide and Fludarabine.
Phase 1 Dose Level	CAR.5/IL15-transduced CB-NK cells	CAR.5/IL15-transduced CB-NK cells Dose level 1, 1e7 cryopreserved cells flat dose Dose level 2, 1e8 cryopreserved cells flat dose Dose level 3, 1e9 cryopreserved cells flat dose Dose level 4, 1e10 cryopreserved cells flat dose All patients will receive Lymphodepleting Chemotherapy of Cyclophosphamide and Fludarabine.
Phase 1 Dose Level	Fludarabine Phosphate	CAR.5/IL15-transduced CB-NK cells Dose level 1, 1e7 cryopreserved cells flat dose Dose level 2, 1e8 cryopreserved cells flat dose Dose level 3, 1e9 cryopreserved cells flat dose Dose level 4, 1e10 cryopreserved cells flat dose All patients will receive Lymphodepleting Chemotherapy of Cyclophosphamide and Fludarabine.
Phase 1 Dose Level	Cyclophosphamide	CAR.5/IL15-transduced CB-NK cells Dose level 1, 1e7 cryopreserved cells flat dose Dose level 2, 1e8 cryopreserved cells flat dose Dose level 3, 1e9 cryopreserved cells flat dose Dose level 4, 1e10 cryopreserved cells flat dose All patients will receive Lymphodepleting Chemotherapy of Cyclophosphamide and Fludarabine.
Phase 2 Dose Level	Cyclophosphamide	Patients will be randomized between the 2 optimal doses of CAR.5/IL15-transduced CB-NK cells determined by Phase 1. All patients will receive Lymphodepleting Chemotherapy of Cyclophosphamide and Fludarabine.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0.	through study completion, an average of 1 year	General grading: Grade 1: Mild: discomfort present with no disruption of daily activity, no treatment required beyond prophylaxis.; Grade 2: Moderate: discomfort present with some disruption of daily activity, require treatment.; Grade 3: Severe: discomfort that interrupts normal daily activity, not responding to first line treatment.; Grade 4: Life Threatening: discomfort that represents immediate risk of death

Trial Locations

Locations (1)

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States