TCR Modified T Cells MDG1011 in High Risk Myeloid and Lymphoid Neoplasms

INCLUSION CRITERIA: 1. Signed written informed consent prior to any clinical trial-related activities 2. Documented diagnosis with the last disease staging within the last 4 weeks prior to screening 3. Human leukocyte antigen (HLA): 1. Phase I and Phase II (treatment group): Subjects positive for HLA-A\*02:01 according to genotyping results 2. Phase II (concurrent control group): Subjects negative for HLA-A\*02:01 according to genotyping results 4. Age ≥ 18 years 5. Life expectancy of at least 4 months. 6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 7. Subjects not planned for allogeneic HSCT (e.g. based on disease characteristics or subject characteristics). Bridging to an allogeneic HSCT will be allowed. 8. Females of childbearing potential must have a negative serum beta human chorionic gonadotropin (β-hCG) pregnancy test result before leukapheresis and before administration of lymphodepleting chemotherapy. Females of non-childbearing potential are those who are postmenopausal greater than 2 years or who have had a bilateral tubal ligation or hysterectomy. 9. Females of childbearing potential and males who have partners of childbearing potential must agree to use an effective contraception method during the clinical trial and for 6 months following the last dose of IMP. Effective birth control includes: 1. intrauterine device plus 1 barrier method; or (b) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm). AML-SPECIFIC INCLUSION CRITERIA: 1. No Complete remission/response (CR) or Complete remission with incomplete hematologic recovery (CRi) after completion of at least 2 cycles of intensive induction chemotherapy or 1 cycle of intensive induction and consolidation (intermediate or high dose cytarabine) chemotherapy each and/or 2. No CR or no CRi after completion of at least 1 cycle of intensive induction chemotherapy including at least 5 days of cytarabine 100-200 mg/m\^2 continuously or an equivalent regimen with cytarabine with total dose not less than 500 mg/m\^2 per cycle and at least 2 days of an anthracycline (e.g. daunorubicine, idarubicin), unable to undergo allogeneic HSCT and/or 3. Refractory disease (including stable disease \[SD\], progressive disease \[PD\]) or relapsed disease after hypomethylating agent therapy (e.g. azacitidine, decitabine) and/or 4. Any SD, partial response (PR), CRi, CR obtained after re-induction or salvage-therapy and/or 5. Relapsed AML patients unable to undergo allogeneic HSCT and/or 6. Relapsed AML after allogeneic HSCT 1. at least 100 days after transplant 2. no evidence of active acute or chronic GvHD at enrolment 3. in case of history of acute (\> overall grade 1) or chronic GvHD (moderate/severe) requiring immunosuppression treatment, no immunosuppression within the last 3 months 4. no immunosuppression (with the exception of low dose steroids \<= 10 mg prednisone or equivalent) 4 weeks before enrolment and ongoing and 7. Myeloid blasts must positively express PRAME MDS-SPECIFIC INCLUSION CRITERIA: 1. IPSS INT-2 or High Grade MDS Excess Blasts-2 (EB-2) not responding to at least 6 courses of azacitidine or 4 courses of decitabine and/or 2. IPSS INT-1, INT-2 or High Grade MDS with recurrence after initial response and 3. Blasts must positively express PRAME MM-SPECIFIC INCLUSION CRITERIA: 1. Relapsed and refractory multiple myeloma: • Progressive MM, also defined as relapsed disease, defined as: 1. A 25% increase from baseline in the serum M-protein (absolute increase * 0.5 g/dL), urine M-protein (absolute increase \> 200 mg/day), and/or the difference between involved and uninvolved free light chain levels (absolute increase ≥ 10 mg/dL). 2. The presence of definite new bone lesions and/or soft tissue plasmacytomas with a clear increase in the size of existing plasmacytomas, or hypercalcemia, that cannot be attributed to another cause. • Relapsed and refractory MM is defined as disease progression within 60 days of a patient's last treatment where at least a minimal response was achieved. • Primary refractory MM is defined as disease that fails to achieve at least a minimal response with any therapy. and 2. At least 3 previous therapy lines with at least one proteasome inhibitor and one immunomodulatory derivate (IMiDs). Induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single regimen. and 3. Myeloma cells must positively express PRAME CRITERIA FOR PRE-EMPTIVE LEUKAPHERESIS PROCEDURE • subject is positive for HLA-A\*02:01 and their blasts/myeloma cells express PRAME • subject fulfills at least some inclusion criteria and, based on the judgement of the investigator, have a likelihood of being eligible for IMP administration in the further course of the subjects disease * subject does not fulfill any exclusion criterion that would be considered permanent (i.e. irreversible organ function impairment) and therefore would certainly preclude the subject from receiving the IMP in the future EXCLUSION CRITERIA: <!-- --> 1. Subjects with acute promyelocytic leukemia exhibiting t(15;17)(q22;q12); PML-RARA, or with variant translocations 2. Pregnant or lactating women 3. Known positive for HIV, active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection 4. Any clinically significant, advanced or unstable disease or inadequate main organ function that may put the subject at special risk, such as: a. creatinine \> 2.0 times the upper normal serum level b. total bilirubin, ALT, AST \>3 times the upper normal serum level c. cardiac left ventricular ejection fraction \< 40% at rest d. severe restrictive or obstructive lung disease 5. History of haploidentical allogeneic stem cell transplantation 6. Subjects both with urinary outflow obstructions and on dialysis or subjects for whom cyclophosphamide is contraindicated for other reasons 7. Clinical significant and ongoing immune suppression including, but not limited to: immunosuppressive agents such as cyclosporine or corticosteroids (at an equivalent dose of \>= 10 mg prednisone per day). Inhaled steroid and physiological replacement for adrenal insufficiency is allowed. 8. Subjects with currently active autoimmune disease. 9. Subjects with a history of primary immunodeficiency. 10. Subjects with a currently active second malignancy other than non- melanoma skin cancers or subjects with history of prior malignancy and previously treated with a curative intent therapy less than 1 year ago 11. Known or suspected hypersensitivity or intolerance to IMP, cyclophosphamide, fludarabine and/or tocilizumab or to any of the excipients 12. Participation in any clinical trial \< 60 days prior to first IMP administration in case of antibodies and \< 14 days for all other IMPs 13. Vulnerable subjects and/or subjects unwilling or unable to comply with procedures required in this clinical trial protocol MM-SPECIFIC EXCLUSION CRITERIA FOR PHASE I AND PHASE II (TREATMENT GROUP): 1. Prior therapy with IMiDs within 14 days prior to leukapheresis and/or infusion of IMP 2. Prior therapy with corticosteroids within 7 days prior to leukapheresis or 7 days prior to infusion of IMP EXCLUSION CRITERIA FOR TREATMENT WITH IMP IN PHASE I AND PHASE II (TREATMENT GROUP): 1. Uncontrolled central nervous system (CNS) disease 2. Uncontrolled infections or uncontrolled disseminated intravascular coagulation; however, if these problems resolve, the start of treatment can be initiated on a delayed schedule 3. Ongoing 3 grade cardiac, renal, pulmonary, gastrointestinal or hepatic toxicities according to CTCAE v4.03; however, if these problems resolve, the start of treatment can be initiated on a delayed schedule 4. Evidence of acute or chronic GvHD