ACHIEVE2 - Safety and Preliminary Efficacy of Intravenous TCB008 in Patients With Relapse or Refractory Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)/AML

NCT06463327 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: TCB008-003
• Study Type: interventional
• Target: 69
• Locations: 0 countries
• Sites: N/A

Brief Summary

TCB008-003 (ACHIEVE2) is an open-label, multi-center study conducted in 2 parts (dose escalation followed by dose expansion) to evaluate safety, persistence/expansion, and preliminary efficacy of single and multiple intravenous doses of TCB008 in patients with Relapse or Refractory Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)/AML, who have failed or are intolerant to the current standard of care. The dose escalation will follow a 3+3 design with 3 cohorts planned. Once the recommended dose for further investigation has been confirmed, based on dose-limiting toxicities (DLTs), overall safety data, and preliminary efficacy data, up to 20 patients will be enrolled to into one of each of the three dose expansion cohorts.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (3)

• Recommended Dose of TCB008 for Dose-Expansion

  To establish the recommended dose for further investigation in the dose-expansion part of the study, in patients with relapsed or relapsed refractory AML or MDS/AML, or MRD persistent-AML or MDS/AML (dose escalation part only).

  The total duration of study participation for each patient (from screening through end of study visit) is anticipated to be approximately 29 months

• Safety and Tolerability of TCB008

  Incidence and severity of dose-limiting toxicities (DLTs). The severity grade will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0. Cytokine release syndrome and neurotoxicity will be graded per American Society for Transplantation and Cellular Therapy (ASTCT) criteria.

  The total duration of study participation for each patient (from screening through end of study visit) is anticipated to be approximately 29 months

• Safety and Tolerability of TCB008

  Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs). Severity of all AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

  The total duration of study participation for each patient (from screening through end of study visit) is anticipated to be approximately 29 months

Secondary Outcomes (1)

• Preliminary Antitumor Activity of TCB008

  The total duration of study participation for each patient (from screening through end of study visit) is anticipated to be approximately 29 months

Other Outcomes (6)

• Expansion and Persistence of γδ T cells in Peripheral Blood and/or Bone Marrow

  The total duration of study participation for each patient (from screening through end of study visit) is anticipated to be approximately 29 months

• Evaluate Measurable Residual Disease (MRD) during and after therapy with TCB008

  The total duration of study participation for each patient (from screening through end of study visit) is anticipated to be approximately 29 months

• Immunogenicity of TCB008

  The total duration of study participation for each patient (from screening through end of study visit) is anticipated to be approximately 29 months

Study Arms (1)

Dose Escalation

EXPERIMENTAL

Drug product: TCB008 Administration route: Intravenous infusion Proposed Dose Limits (DL) for dose escalation: * Cohort 1: 1.5 mL IV TCB008 (3.6×107 to 6.9×107 cells) * Cohort 2: up to 5 mL IV TCB008 (12.0×107 to 23.0×107 cells) * Cohort 3: up to 18 mL IV TCB008 (43.2×107 to 82.8×107 cells) The DL for the dose expansion will be based on the recommended dose for expansion determined in the dose escalation part of the study Dosing is intended to be fixed (i.e., not weight-based or body surface area-based). In both the dose escalation and dose expansion parts of the study, participants may be reinfused with TCB008 up to 3 times following initial infusion, if deemed appropriate by the investigator (or designee) based on review of available safety data and confirmation of disease status. In the case that TCB008 is reinfused each dose will be administered 29 days apart.

Drug: TCB008

Interventions

TCB008 DRUG

TCB008 is derived from the peripheral blood mononuclear cells (PBMCs) of unrelated, healthy donors and consists of expanded cluster designation (CD)3+ T cells expressing the γ chain variable region 9 δ-chain variable region 2 (Vγ9Vδ2) T cell receptor (TCR); it is infused into patients to boost their immune system. It is currently developed for treatment of cancers and infectious diseases.

Also known as: CD3+ T cells expressing the γ-chain variable region 9 δ-chain variable region 2 (Vγ9Vδ2) T cell receptor (TCR)

Dose Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must satisfy all the following criteria at the screening visit unless otherwise stated:
• Male or female ≥18 years of age at the time of signing the ICF
• Body weight ≥50 kg
• Male patients and female patients of childbearing potential will agree to abide by the contraception requirements defined in the protocol
• Diagnosis of primary AML, AML with myelodysplasia-related changes, or MDS/AML (10% to 19% blasts in BM or peripheral blood) according to World Health Organization23 classification as determined by pathology review at the treating institution
• Patients with AML who have relapsed or have refractory disease after at least one prior line of therapy and for whom there are no standard-of-care options, such that patients meet 1 of the following criteria (a to c) in the escalation part of the study or specified criteria for each cohort in the expansion part of the study:
• Refractory disease not achieving CR, CRh, or CRi after at least 2 courses of intensive induction treatment or after a defined response landmark for less intensive treatments (Cohort 4 and Cohort 6 \[only patients with adverse risk per ELN guidelines 202223\] for the expansion part of the study)
• Relapsed disease within 1 year after achieving CR, CRh, or CRi, where relapse is defined as 5% or more BM blasts that are not attributable to any other cause, reappearance of blasts in the blood in at least 2 peripheral blood samples collected at least one week apart, or development of extramedullary disease (Cohort 4 and Cohort 6 \[only patients with adverse risk per ELN guidelines 202223\] for the expansion part of the study)
• Previous treated AML or MDS/AML that achieves CR with MRD+ (Cohort 5 for the expansion part of the study)
• Eastern Cooperative Oncology Group (ECOG) performance status between 0 and 2
• Adequate coagulation, defined as activated partial thromboplastin time and prothrombin time or international normalized ratio ≤1.5 × upper limit of normal (ULN)
• Adequate hepatic function, defined as:
• alanine aminotransferase or aspartate aminotransferase ≤2.5 × ULN or ≤5 × ULN with documented liver involvement
• total bilirubin ≤1.5 × ULN or ≤3 × ULN with documented liver involvement. If total bilirubin is \>1.5 × ULN then direct/indirect or conjugated/unconjugated bilirubin tests should be performed and meet the parameter specified. For patients with hemolysis and/or Gilbert's syndrome, they may be enrolled if unconjugated/indirect bilirubin is \<5 × ULN.
• Adequate renal function defined by serum creatinine up to 1.5 × ULN.

You may not qualify if:

• Patients will be excluded from the study if they satisfy any of the following criteria, as applicable, at screening unless otherwise stated:
• Medical Conditions
• Major surgery within 4 weeks prior to the planned start of lymphodepletion
• Patients with a history of symptomatic deep vein thrombosis or pulmonary embolism requiring anticoagulation therapy within 6 months prior to enrollment
• Hypersensitivity to iron-dextran, murine antibodies, or any of the agents used in this study
• History of allogeneic or autologous SCT or any other organ transplant or chimeric antigen receptor-modified T cell therapy within the 60 days prior to the start of lymphodepletion (Day 6) or with any of the following:
• active GVHD of any grade
• need for anticytokine therapy for toxicity from CAR-T therapy; residual symptoms of neurotoxicity \>CTCAE Grade 1 from CAR-T therapy
• ongoing immunosuppressive therapy.
• Clinically active central nervous system leukemia or prior history of CTCAE Grade ≥3 drug-related central nervous system toxicity
• Evidence of moderate to severe forms of primary immunodeficiencies. Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura) where it is required to introduce new therapy or escalate concomitant therapy within the 4 weeks prior to the start of lymphodepletion (Day 6) in order to maintain adequate blood counts
• History of autoimmune disease resulting in significant end-organ disease or requiring systemic immunosuppression and/or systemic disease-modifying agents within the last 1 year:
• patients who receive a physiologic dose of steroid (prednisolone \[or equivalent\] 7.5mg/day or equivalent) are eligible for study participation
• patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible for study participation
• patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for study participation

Sponsors & Collaborators

• TC Biopharm: lead

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Receptors, Antigen, T-Cell

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Receptors, Antigen; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2024
• First Posted: June 17, 2024
• Study Start: January 1, 2025
• Primary Completion: June 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: June 17, 2024

Record last verified: 2024-06