A dose-escalation, open label phase I study to assess the safety, feasibility and preliminary efficacy of HA-1H TCR modified T cells, MDG1021, in patients with relapsed or persistent hematologic malignancies after allogeneic hematological stem cell transplantation with or without unmanipulated donor lymphocyte infusion.

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 29

Inclusion Criteria

1. 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.
2. Patients positive for HLA-A*02:01 according to genotyping results
3. Patients positive for HA-1H
4. Patients who received the allo-HSCT at least 100 days preceding the
leukapheresis
5. Patients (i.e. recipient) transplanted with a sibling or unrelated HSCT
donor
a. donor being HLA-A*02:01 positive and HA-1H negative, or
b. 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
6. Age >= 18 years, of either sex
7. (Eastern Cooperative Oncology Group) ECOG performance status 0-2.
8. Life expectancy of at least 3 months
9. Patients must be able to understand and be willing to give signed informed
consent

Exclusion Criteria

1. Evidence of acute or chronic graft versus host disease (GVHD) >= grade II
2. 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
3. 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:
a. Creatinine > 2.5 times the upper limit of normal (ULN) serum level
b. Total bilirubin, ALAT, ASAT > 3.0 x ULN serum level
c. Cardiac left ventricular ejection fraction < 35% at rest
d. Severe restrictive or obstructive lung disease
4. 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
5. Patients with a history of primary immunodeficiency
6. 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
7. Patients both with urinary outflow obstructions and on dialysis or patients
for whom cyclophosphamide is contraindicated for other reasons
8. Known or suspected hypersensitivity or intolerance to IMP, cyclophosphamide,
fludarabine and/or tocilizumab or to any of the excipients
9. Participation in any clinical study < 60 days prior to first IMP
administration in case of antibodies and < 14 days for all other IMPs
10. Vulnerable patients and/or patients unwilling or unable to comply with
procedures required in this clinical study protocol
11. Pregnant or lactating women
12. 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
13. Fertile men not agreeing to use effective contraceptive methods during the
clinical study

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>DOSE-ESCALATION PART OF THE STUDY<br /><br>Primary endpoints:<br /><br>• Incidence and severity of adverse events (AE) at 28 days according to the<br /><br>CTCAE v5.0<br /><br>• MTD and/or RP2D of MDG1021 as determined by DLTs up to 28 days post<br /><br>transfusion.<br /><br>EXPANSION PART OF THE STUDY<br /><br>Primary endpoint:<br /><br>• Incidence and severity of adverse events (AE) of MDG1021 at the RP2D at 28<br /><br>days according to the CTCAE v5.0</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>ENDPOINTS FOR BOTH PARTS OF THE STUDY<br /><br>Secondary endpoints: all assessed at day 28, and months 3, 6, and 12, unless<br /><br>specified otherwise.<br /><br>• Incidence and severity of adverse events (AEs) >= grade 3 only at day 28<br /><br>according to the NCI CTCAE v5.0<br /><br>• ORR<br /><br>• OS<br /><br>• PFS<br /><br>• DoR<br /><br>• Quality of life assessed by using the EQ-5D-5L (EuroQol) also before IMP<br /><br>administration, but not at day 28</p><br>