AML, CML, MM, ALL, MDS, MPN, MF and malignant B- or T-cell lymphoma blood disease haematologic malignancies
Conditions
Interventions
MDG1021, the IMP, is a gene modified ATMP which contains autologous T cells, 
expressing the HLA-A*02:01 restricted TCR targeting HA-1H, in a 0.9% saline 
solution with human serum albumin in a total volume of 100 mL in a standard 
infusion bag.
Three dose levels of MDG1021 will be investigated to determine the RP2D. The 
following dose levels will be administered by a single intravenous (IV) 
transfusion up to 30 minutes:
• D1: target dose of 0.3x10^6 HA-1H transduced T cells/kg BW ±20% in 100 mL 
• D2: target dose of 1x10^6 HA-1H transduced T cells/kg BW ±20% in 100 mL 
• D3: target dose of up to 3x10^6 HA-1H transduced T cells/kg BW ±20% in 100 
mL, whereas the lower range for D3 is >
D2 (i.e. >
1.2x10^6)
The following rules apply to IMP administration:
• Dose calculation will not be increased above 120 kg body weight.
• In case of BW decrease of >
20% between screening and IMP administration the 
dose will be adjusted by limiting the infused volume of the IMP accordingly to 
the maximum dose allowed
• In case of a serious intolerability event it should be evaluated, according 
to the patient situation and the administered dose, whether the IMP 
administration should continue, interrupted or discontinued. A rescue therapy 
correlating to the seriousness of symptoms should be initiated when appropriate.
• Manufacturing could potentially result in an out of specification (OOS) 
product, however, since this is a patient derived, patient specific, last 
treatment option material, every effort will be made to make it available for 
treatment due to ethical reasons: 
Sponsors
Miltenyi Biomedicine
Eligibility
Inclusion criteria
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
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 ß-hCG test is required at baseline 13. Fertile men not agreeing to use effective contraceptive methods during the clinical study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| DOSE-ESCALATION PART OF THE STUDY Primary endpoints: • Incidence and severity of adverse events (AE) at 28 days according to the CTCAE v5.0 • MTD and/or RP2D of MDG1021 as determined by DLTs up to 28 days post transfusion. EXPANSION PART OF THE STUDY Primary endpoint: • Incidence and severity of adverse events (AE) of MDG1021 at the RP2D at 28 days according to the CTCAE v5.0 | — |
Secondary
| Measure | Time frame |
|---|---|
| ENDPOINTS FOR BOTH PARTS OF THE STUDY Secondary endpoints: all assessed at day 28, and months 3, 6, and 12, unless specified otherwise. • Incidence and severity of adverse events (AEs) >= grade 3 only at day 28 according to the NCI CTCAE v5.0 • ORR • OS • PFS • DoR • Quality of life assessed by using the EQ-5D-5L (EuroQol) also before IMP administration, but not at day 28 | — |
Countries
Netherlands
Outcome results
None listed