Gamma Delta T-cell Infusion for AML at High Risk of Relapse After Allo HCT

H. Lee Moffitt Cancer Center and Research Institute

Status and phase: Active, not recruiting; Phase 1

Conditions: Acute Myeloid Leukemia

Treatments: Biological: Gamma Delta T-Cell Infusion

Study type: Interventional

Funder types: Other

Identifiers

NCT05015426

9BC08 (Other Grant/Funding Number)

MCC-20305

Details and patient eligibility

About

The purposes of the study are to determine the maximum tolerated dose (MTD) and effectiveness of Artificial Antigen Presenting Cell (AAPC)-expanded donor T-cells administered as a single infusion after an allogeneic hematopoietic cell transplant (alloHCT) to treat patients with Acute Myeloid Leukemia (AML).

Enrollment: 20 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female, aged between 18 and 75 years of age undergoing allogeneic hematopoietic stem cell transplantation (alloHCT) or the treatment ELN 2017 adverse risk AML
• Have < 5% blasts in bone marrow by morphology at the time of transplantation. Patients with pre-alloHCT or post-alloHCT flow cytometric or molecular evidence of MRD are allowed
• Karnofsky performance status (KPS) ≥ 70% during the study screening.
• Free of symptomatic congestive heart failure or uncontrolled arrhythmia
• Adequate organ function as defined per protocol
• Negative serum pregnancy test
• Note: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for at least 30 days following study treatment (T-cell infusion); should a woman subject or female partner of a male subject become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately.
• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Agreement to adhere to Lifestyle Considerations throughout study duration

Exclusion criteria

• Current use of concomitant systemic glucocorticoid at the time of γδ T-cell infusion for any reason will not be allowed in order to avoid their immunosuppressive effects on γδ T-cell function.
• Active grade II-IV acute GVHD (patients with prior GVHD should be off prednisone for at least 14 days prior to infusion of the study cell product).
• Uncontrolled serious infection.
• Morphologic relapse of leukemia at any timepoint after HCT.
• Active central nervous system malignancy.
• Pregnancy or lactation.
• Treatment with another investigational drug or other intervention within 14 days of T-cell infusion

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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20 participants in 5 patient groups

Dose Level -1

Experimental group

Description:

Dose Level -1 may be used as a de-escalation dose level due to Dose Limiting Toxicities (DLTs) from Dose Level 1 Participants will receive 1.0 x 106 cells/kg (0.75-1.25 x 106 cells/kg) Artificial Antigen Presenting Cell (AAPC)-expanded donor T-cells administered as a single infusion

Treatment:

Biological: Gamma Delta T-Cell Infusion

Dose Level 1

Experimental group

Description:

Participants will receive 5.0 x 106 cells/kg (3.75-6.25 x 106 cells/kg) Artificial Antigen Presenting Cell (AAPC)-expanded donor T-cells administered as a single infusion

Treatment:

Biological: Gamma Delta T-Cell Infusion

Dose Level 2

Experimental group

Description:

Participants will receive 2.5 x 107 cells/kg (1.875-3.125 x 107 cells/kg) Artificial Antigen Presenting Cell (AAPC)-expanded donor T-cells administered as a single infusion

Treatment:

Biological: Gamma Delta T-Cell Infusion

Dose Level 3

Experimental group

Description:

Participants will receive 1.0 x 108 cells/kg (0.75-1.25 x 108 cells/kg) Artificial Antigen Presenting Cell (AAPC)-expanded donor T-cells administered as a single infusion

Treatment:

Biological: Gamma Delta T-Cell Infusion

Treatment at Maximum Tolerated Dose

Experimental group

Description:

Participants will receive Artificial Antigen Presenting Cell (AAPC)-expanded donor T-cells at the dose determined to be the Maximum Tolerated Dose, administered as a single infusion

Treatment:

Biological: Gamma Delta T-Cell Infusion