Non-Hodgkin Lymphoma
Conditions
Keywords
lymphoma, GDA-201, NK cells, rituximab, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse
Brief summary
This is an open-label, non-randomized, interventional, single group assignment study of GDA-201, an allogeneic cryopreserved Natural Killer (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).
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.
Interventions
DRUGGDA-201
NAM-expanded allogeneic NK cells
Sponsors
Gamida Cell ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose escalation cohort 1 to reach the maximal tolerated dose, followed by cohort 2 using the recommended Phase II Dose
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients must have relapsed/refractory FL or HGBCL/DLBCL that has failed conventional therapy defined as follows: 1. Received at least 2 prior lines of therapy 2. Transplant ineligible patients allowed assuming they meet criterion a. 3. 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 4. FL transformed to HGBCL: Must have received at least 1 line of therapy after transformation to DLBCL/HGBCL 2. Patients must be at least 18 years of age 3. Patients must have adequate hematologic, hepatic, renal, cardiac and pulmonary function prior to any study treatment.
Exclusion criteria
1. Central Nervous System (CNS) lymphoma 2. Time between previous treatment and first dose of study treatment (rituximab): 1. Allogeneic hematopoietic stem cell transplantation (HSCT) \< 6 months prior to study treatment 2. Autologous HSCT \< 3 months prior to study treatment 3. CAR-T \< 2 months prior to study treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase I: 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. acute graft-versus-host disease (aGvHD) will be assessed according to the Consensus Conference on aGvHD 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 extend |
| Phase II: Overall Response Rate | up to 1 year | Patients will be assessed after the infusion of GDA-201 for level of response. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GDA-201 - Cohort 1 (Phase I) - Dose Level 1 Phase I dose escalation with up to 4 dose levels to reach MTD and determine recommended Phase II dose (RP2D).
Dose Level 1: GDA-201 2.5x10\^7 cells/kg | 4 |
| GDA-201 - Cohort 1 (Phase I) - Dose Level 2 Phase I dose escalation with up to 4 dose levels to reach MTD and determine recommended Phase II dose (RP2D).
Dose Level 2: GDA-201 5x10\^7 cells/kg | 3 |
| GDA-201 - Cohort 1 (Phase I) - Dose Level 3 Phase I dose escalation with up to 4 dose levels to reach MTD and determine recommended Phase II dose (RP2D).
Dose Level 3: GDA-201 2.5x10\^8 cells/kg | 3 |
| GDA-201 - Cohort 1 (Phase I) - Dose Level 4 Phase I dose escalation with up to 4 dose levels to reach MTD and determine recommended Phase II dose (RP2D).
Dose Level 4: GDA-201 5x10\^8 cells/kg | 3 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Dose Level 4 (Week 62 - Week 114) | Early termination by Sponsor | 0 | 0 | 0 | 3 |
Baseline characteristics
| Characteristic | GDA-201 - Cohort 1 (Phase I) - Dose Level 1 | GDA-201 - Cohort 1 (Phase I) - Dose Level 2 | GDA-201 - Cohort 1 (Phase I) - Dose Level 3 | GDA-201 - Cohort 1 (Phase I) - Dose Level 4 | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 6 Participants |
| Patient diagnosis Diffuse large B-cell lymphoma | 2 Participants | 1 Participants | 0 Participants | 2 Participants | 5 Participants |
| Patient diagnosis Follicular lymphoma | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Patient diagnosis High grade B-cell lymphoma | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants |
| Patient diagnosis Mantle cell lymphoma | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Patient diagnosis Marginal zone lymphoma | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 12 Participants |
| Region of Enrollment United States | 4 participants | 3 participants | 3 participants | 3 participants | 13 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 6 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 3 | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 4 / 4 | 3 / 3 | 3 / 3 | 3 / 3 |
| serious Total, serious adverse events | 2 / 4 | 1 / 3 | 1 / 3 | 0 / 3 |
Outcome results
Primary
Phase II: Overall Response Rate
Patients will be assessed after the infusion of GDA-201 for level of response.
Time frame: up to 1 year
Population: Study was early terminated by Sponsor prior to initiation of the phase II
Primary
Phase I: Safety as Determined by Dose Limiting Toxicities (DLTs)
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. acute graft-versus-host disease (aGvHD) will be assessed according to the Consensus Conference on aGvHD 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 extend
Time frame: Day 28
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GDA-201 - Cohort 1 (Phase I) - Dose Level 1 | Phase I: Safety as Determined by Dose Limiting Toxicities (DLTs) | Patients who experienced dose limiting toxicities (DLTs) | 0 Participants |
| GDA-201 - Cohort 1 (Phase I) - Dose Level 1 | Phase I: Safety as Determined by Dose Limiting Toxicities (DLTs) | Patients not evaluable for DLT | 1 Participants |
| GDA-201 - Cohort 1 (Phase I) - Dose Level 1 | Phase I: Safety as Determined by Dose Limiting Toxicities (DLTs) | Patients who did not experience DLT | 3 Participants |
| GDA-201 - Cohort 1 (Phase I) - Dose Level 2 | Phase I: Safety as Determined by Dose Limiting Toxicities (DLTs) | Patients who experienced dose limiting toxicities (DLTs) | 0 Participants |
| GDA-201 - Cohort 1 (Phase I) - Dose Level 2 | Phase I: Safety as Determined by Dose Limiting Toxicities (DLTs) | Patients not evaluable for DLT | 0 Participants |
| GDA-201 - Cohort 1 (Phase I) - Dose Level 2 | Phase I: Safety as Determined by Dose Limiting Toxicities (DLTs) | Patients who did not experience DLT | 3 Participants |
| GDA-201 - Cohort 1 (Phase I) - Dose Level 3 | Phase I: Safety as Determined by Dose Limiting Toxicities (DLTs) | Patients who did not experience DLT | 3 Participants |
| GDA-201 - Cohort 1 (Phase I) - Dose Level 3 | Phase I: Safety as Determined by Dose Limiting Toxicities (DLTs) | Patients who experienced dose limiting toxicities (DLTs) | 0 Participants |
| GDA-201 - Cohort 1 (Phase I) - Dose Level 3 | Phase I: Safety as Determined by Dose Limiting Toxicities (DLTs) | Patients not evaluable for DLT | 0 Participants |
| GDA-201 - Cohort 1 (Phase I) - Dose Level 4 | Phase I: Safety as Determined by Dose Limiting Toxicities (DLTs) | Patients who experienced dose limiting toxicities (DLTs) | 0 Participants |
| GDA-201 - Cohort 1 (Phase I) - Dose Level 4 | Phase I: Safety as Determined by Dose Limiting Toxicities (DLTs) | Patients not evaluable for DLT | 1 Participants |
| GDA-201 - Cohort 1 (Phase I) - Dose Level 4 | Phase I: Safety as Determined by Dose Limiting Toxicities (DLTs) | Patients who did not experience DLT | 2 Participants |