HA-1H TCR T Cell for Relapsed/Persistent Hematologic Malignancies After Allogeneic Stem Cell Transplantation

NCT04464889 | Withdrawn Phase 1 DMC

• 1 other identifier: CD-TCR-003
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a non-randomised, open-label phase I study of an investigational medicinal product (IMP) consisting of a HLA-A\*02:01 restricted HA-1H T cell receptor transduced T cell (MDG1021) immunotherapy for relapsed or persistent hematologic malignancies after allogeneic hematopoietic stem cell transplantation. The aim of the study is to determine the recommended phase II dose of MDG1021.

Conditions

Acute Myeloid Leukemia; Acute Lymphoid Leukemia; Myelodysplastic Syndromes; Myeloproliferative Disorders; Chronic Myeloid Leukemia; Myelofibrosis; Multiple Myeloma; Malignant Lymphoma

Keywords

Allogeneic hematopoietic stem cell transplantation; Relapsed hematologic malignancy; Persistent hematologic malignancy

Outcome Measures

Primary Outcomes (4)

• Safety and tolerability of HA-1H TCR transduced T cells: incidence and severity of adverse events

  To assess the incidence and severity of adverse events during the dose escalation part of the study according to the NCI CTCAE v5.0

  up to 28 days after T cell infusion

• Maximum tolerated dose (MTD) of HA-1H TCR transduced T cells

  To asses the maximum tolerated dose (MTD) of MDG1021 as determined by dose-limiting toxicities (DLTs)

  up to 28 days after T cell infusion

• Recommended phase 2 dose (RP2D) of HA-1H TCR transduced T cells

  To asses the recommended phase II dose (RP2D) of MDG1021

  up to 28 days after T cell infusion

• Safety and tolerability of HA-1H TCR transduced T cells at recommended phase II dose: incidence and severity of adverse events

  To assess the incidence and severity of adverse events of MDG1021 at the RP2D during the expansion part of the study according to the NCI CTCAE v5.0

  up to 28 days after T cell infusion

Secondary Outcomes (7)

• Safety and tolerability (both parts of the study): incidence and severity of adverse events

  Up to 12 months after T cell infusion

• Overall response rate

  Up to 12 months after T cell infusion

• Overall survival

  Up to 12 months afterT cell infusion

• Progression free survival

  Up to 12 months afterT cell infusion

• Duration of response

  Up to 12 months afterT cell infusion

Other Outcomes (7)

• Feasibility of manufacturing HA-1H TCR transducer T cells: proportion of patients for whom leukapheresis was feasible

  Up to Day 0 after T cell infusion

• Persistence and expansion of HA-1H transduced T cells in peripheral blood

  Up to 12 months afterT cell infusion

• Function of HA-1H TCR transduced T cells detectable in peripheral blood

  Up to 12 months afterT cell infusion

Study Arms (1)

MDG1021

EXPERIMENTAL

Dose-escalation part of the study to investigate 3 MDG1021 doses. Dose-expansion part of the study to investigate the selected optimal MDG1021 dose.

Drug: MDG1021 dose 1; Drug: MDG1021 dose 2; Drug: MDG1021 dose 3; Drug: MDG1021 optimal dose

Interventions

MDG1021 dose 1 DRUG

3 patients to receive dose1: target dose of 0.3x10\^6 HA-1H TCR transduced T cells/kg BW ±20% in 100 mL

MDG1021

MDG1021 dose 2 DRUG

3 patients to receive dose 2: target dose of 1x10\^6 HA-1H TCR transduced T cells/kg BW ±20% in 100 mL

MDG1021

MDG1021 dose 3 DRUG

3 patients to receive dose 3: target dose of 3x10\^6 HA-1H TCR transduced T cells/kg BW +20% in 100 mL

MDG1021

MDG1021 optimal dose DRUG

20 patients to receive the selected optimal dose

MDG1021

Eligibility Criteria

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

You may qualify if:

• Relapsed or persistent disease is defined according to disease specific guidelines (AML, CML, MM, ALL, MDS, MPN, MF and malignant B- or T-cell lymphoma) and includes MRD positivity.
• Patients positive for HLA-A\*02:01 according to genotyping results
• Patients positive for HA-1H
• Patients who received the allo-HSCT at least 100 days preceding the leukapheresis
• Patients (i.e. recipient) transplanted with a sibling or unrelated HSCT donor
• donor being HLA-A\*02:01 positive and HA-1H negative, or
• a donor with a single mismatch at HLA-A\*02:01, being HA-1H positive or negative
• Patients from whom at least 10x10\^6 donor CD8+ T cells can be harvested by leukapheresis
• Age ≥ 18 years, of either sex
• ECOG performance status 0-2.
• Life expectancy of at least 3 months
• Patients must be able to understand and be willing to give signed informed consent

You may not qualify if:

• Evidence of acute or chronic graft versus host disease (GVHD) ≥ grade II
• Serologic evidence of acute or chronic hepatitis B virus infection (i.e. positive for HBsAg or IgM anti-HBc). Positive HIV and HCV serology or active bacterial infection
• Medical or psychological conditions that would make the patient unsuitable candidate for cell therapy at the discretion of the investigator. Special risks to be considered:
• Creatinine \> 2.5 times the upper limit of normal (ULN) serum level
• Total bilirubin, ALAT, ASAT \> 3.0 x ULN serum level
• Cardiac left ventricular ejection fraction \< 35% at rest
• Severe restrictive or obstructive lung disease
• Clinically significant and ongoing immune suppression including, but not limited to immunosuppressive agents (e.g. cyclosporine or corticosteroids (at an equivalent dose of ≥ 10 mg prednisone per day)). Inhaled steroid and physiological replacement for adrenal insufficiency is allowed
• Patients with a history of primary immunodeficiency
• Patients with a currently active second malignancy other than nonmelanoma skin cancers or subjects with history of prior malignancy and previously treated with a curative intent therapy less than 1 year ago
• Patients both with urinary outflow obstructions and on dialysis or patients for whom cyclophosphamide is contraindicated for other reasons
• Known or suspected hypersensitivity or intolerance to IMP, cyclophosphamide, fludarabine and/or tocilizumab or to any of the excipients
• Participation in any clinical study \< 60 days prior to first IMP administration in case of antibodies and \< 14 days for all other IMPs
• Vulnerable patients and/or patients unwilling or unable to comply with procedures required in this clinical study protocol
• Pregnant or lactating women

Sponsors & Collaborators

• Medigene AG: lead

Study Sites (1)

Leiden University Medical Centre

Leiden, South Holland, 2333 ZA Leiden, Netherlands

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Myeloproliferative Disorders; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Primary Myelofibrosis; Multiple Myeloma; Lymphoma; Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Neoplasms by Site

Study Officials

• Peter van Balen, MD

  Leiden University Medical Centre

  PRINCIPAL INVESTIGATOR

• Rene Goedkoop, MD

  Medigene AG

  STUDY DIRECTOR

Study Design

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

Model Details: The aim of the study is to determine the recommended phase II dose (RP2D) of MDG1021 that will be determined on the basis of safety and ability to manufacture a cohort specific MDG1021 dose. The dose-escalation part of the study is designed to assess the safety and the MTD of MDG1021, using a standard 3+3 cohort design, with up to 3 additional subjects to be enrolled in case of dose limiting toxicity (DLT). Upon completion of the dose-escalation part of the study, 20 eligible patients will be treated in the expansion part of the study with MDG1021 at the RP2D to further evaluate safety, feasibility and preliminary efficacy.

Study Record Dates

• First Submitted: July 1, 2020
• First Posted: July 9, 2020
• Study Start: July 2, 2020
• Primary Completion: July 1, 2023
• Study Completion: July 1, 2025
• Last Updated: October 8, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)