Status:
WITHDRAWN
HA-1H TCR T Cell for Relapsed/Persistent Hematologic Malignancies After Allogeneic Stem Cell Transplantation
Lead Sponsor:
Medigene AG
Conditions:
Acute Myeloid Leukemia
Acute Lymphoid Leukemia
Eligibility:
All Genders
18+ years
Phase:
PHASE1
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...
Detailed Description
This phase I is designed to assess the safety and feasibility of a HLA-A\*02:01 restricted, HA-1H T cell receptor (TCR) transduced patient-derived T cell (MDG1021) immunotherapy, with secondary endpoi...
Eligibility Criteria
Inclusion
- 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
Exclusion
- 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
- Women of child-bearing potential not using highly effective method(s) of birth control (i.e., with low failure rate \< 1% per year) throughout the study and/or unwilling to be tested for pregnancy. A negative serum β-hCG test is required at baseline
- Fertile men not agreeing to use effective contraceptive methods during the clinical study
- Exclusion criteria at time of IMP administration:
- Uncontrolled central nervous system (CNS) disease
- Uncontrolled, life threatening infections or uncontrolled disseminated intravascular coagulation; however, if these problems resolve, the start of treatment can be initiated on a delayed schedule
- Evidence of acute or chronic graft versus host disease (GVHD) ≥ grade II
- Unable to generate HA-1H TCR transduced T cells for transfusion (out of specification). However, if a lower than planned number of cells is available, the patient will have the option to receive the OOS HA-1H TCR transduced T cells product (cell dose must be at least the lowest dose level of D1 and will be analyzed in the safety and full analysis set populations.
- If not enough starting material is collected during leukapheresis, the patient will be excluded from study participation and receive best available standard therapy.
Key Trial Info
Start Date :
July 2 2020
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
July 1 2025
Estimated Enrollment :
Patients enrolled
Trial Details
Trial ID
NCT04464889
Start Date
July 2 2020
End Date
July 1 2025
Last Update
October 8 2021
Active Locations (1)
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1
Leiden University Medical Centre
Leiden, South Holland, Netherlands, 2333 ZA Leiden