Evaluation of Safety and Efficacy of Allo GDA-201 NK Cells in Patients With Relapsed/Refractory B Cell NHL

Sponsor

Gamida Cell ltd (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05296525

Collaborator

(none)

Enrollment

Locations

Arm

31.9

Anticipated Duration (Months)

24.8

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an open-label, non-randomized, interventional, single group assignment study of GDA-201, an allogeneic cryopreserved NK cell therapy derived from donor peripheral blood, in combination with rituximab, monoclonal anti-CD20 antibody, for patients with relapsed or refractory B Cell non-Hodgkin lymphoma (NHL).

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin Lymphoma	Drug: GDA-201	Phase 1/Phase 2

Detailed Description

The study is divided into a phase I dose escalation phase and a phase II expansion phase.

Patients with relapsed or refractory follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL)/high grade B-cell lymphoma (HGBCL) will receive GDA-201 followed by a short course of low-dose interleukin-2 (IL-2). Rituximab will be administered prior to and after GDA-201 infusion.

Phase I: Dose escalation phase The objective of Phase I is to evaluate the safety of GDA-201 in patients with FL, DLBCL/ HGBCL, marginal zone lymphoma or mantle cell lymphoma. The maximal tolerated dose (MTD) and recommended Phase II Dose (RP2D) will be determined based on dose limiting toxicities (DLT).

Phase II expansion phase The objective of the Phase II expansion cohort is to evaluate the safety and efficacy of GDA-201 in two patient cohorts, FL and DLBCL/HGBCL.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

99 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I/II Multicenter Study Evaluating the Safety and Efficacy of Allogeneic GDA-201 Natural Killer Cells in Patients With Relapsed/Refractory B Cell Non-Hodgkin Lymphoma

Actual Study Start Date :

Jul 5, 2022

Anticipated Primary Completion Date :

Aug 1, 2024

Anticipated Study Completion Date :

Mar 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Other: GDA-201 Phase 1 dose escalation with up to 4 dose levels to reach MTD and determine recommended phase 2 dose (RP2D). Phase 2 RP2D will be administered to all patients.	Drug: GDA-201 NAM-expanded allogeneic NK cells Other Names: NAM NK

Arm

Intervention/Treatment

Other: GDA-201

Phase 1 dose escalation with up to 4 dose levels to reach MTD and determine recommended phase 2 dose (RP2D). Phase 2 RP2D will be administered to all patients.

Drug: GDA-201

NAM-expanded allogeneic NK cells

Other Names:

NAM NK

Outcome Measures

Primary Outcome Measures

Phase 1: Safety as determined by dose limiting toxicities (DLTs) [Day 28]
DLTs defined as one of the following within the first 28 days of the first dose of GDA-201 by the NCI-CTCAE v 5.0. aGvHD will be assessed according to the Consensus Conference on Acute GvHD grading: Steroid refractory Grade II aGvHD, defined as GvHD that does not respond to at least 1 mg/kg/day or equivalent of prednisone within 7 days of initiating therapy Grade III or IV aGvHD Grade 4 infusion reaction Grade 4 or 5 related adverse event (AE) Grade 3 or above cardiac, central nervous system or pulmonary adverse event. Any Grade 3 or above non-hematologic adverse event that does not resolve to Grade 2 or below within 72 hours, except for renal or hepatic adverse events which may take up to 7 days to resolve Treatment emergent ≥Grade 3 autoimmune disorder Grade 3 or above allergic reaction that does not recover to Grade II or below within 24 hours Grade 4 cytopenia lasting beyond Day 42 (the 28-day DLT observation period will be extended to confirm)
Phase 2: overall response rate [up to 1 year]
Patients will be assessed after the infusion of GDA-201 for level of response.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients must have relapsed/refractory FL or HGBCL/DLBCL that has failed conventional therapy defined as follows:
Received at least 2 prior lines of therapy
Transplant ineligible patients allowed assuming they meet criterion a.
Patients who received prior chimeric antigen receptor modified T-cells (CAR-T) cell therapy or are considered ineligible for CAR-T therapy per the investigator's discretion
FL transformed to HGBCL: Must have received at least 1 line of therapy after transformation to DLBCL/HGBCL
Patients must be at least 18 years of age
Patients must have adequate hematologic, hepatic, renal, cardiac and pulmonary function prior to any study treatment.

Exclusion Criteria:

CNS lymphoma
Time between previous treatment and first dose of study treatment (rituximab):
Allogeneic HSCT < 6 months prior to study treatment
Autologous HSCT < 3 months prior to study treatment
CAR-T < 2 months prior to study treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Loyola University, Cardinal Bernardin Cancer Center	Maywood	Illinois	United States	60153
2	Dana-Farber/Mass General Brigham Cancer Care, Inc.	Boston	Massachusetts	United States	02215
3	Henry Ford Medical Center	Detroit	Michigan	United States	48202
4	Regents of the University of Minnesota	Minneapolis	Minnesota	United States	55455