EUCTR2017-000440-18-DE进行中（未招募）1 期
A Phase I/II, Open-Label, Non-Randomized, Multicentre, Dose-Escalation Clinical Trial with Control Group to Evaluate the Safety, Feasibility and Preliminary Efficacy of PRAME TCR Modified T Cells, MDG1011, in Subjects with High Risk Myeloid and Lymphoid Neoplasms - A Phase I/II clinical trial for TCR modified T cells, MDG1011, in HR myeloid and lymphatic neoplasms
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Medigene AG
- 入组人数
- 92
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •Key inclusion criteria include:
- •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)
- •a. Phase I and Phase II (treatment group): Subjects positive for HLA-A*02:01 according to genotyping results
- •b. 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 hematopoetic stem cell transplantation (HSCT) (e.g. based on disease characteristics or subject characteristics). Bridging to an allogeneic HSCT will be allowed.
- •8. Negative pregnancy test in women of childbearing potential (before leukapheresis and before administration of lymphodepleting chemotherapy).
- •9. For fertile men and women, agreement to use effective contraceptive methods during the clinical trial.
- •Acute Myeloid Leukemia (AML)-specific inclusion criteria:
- •1. No complete remission response (CR) or no complete remission with incomplete heamatologic 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),
- •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/m² continuously or an equivalent regimen with cytarabine with total dose not less than 500 mg/m² per cycle and at least 2 days of an anthracycline (e.g. daunorubicin, idarubicin), unable to undergo allogeneic HSCT
- •3. Refractory disease (including stable disease [SD], progressive disease [PD]) or relapsed disease after hypomethylating agent therapy (e.g. azacitidine, decitabine),
- •4. Any SD, partial reponse (PR), CRi, CR obtained after re-induction or salvage therapy,
- •5. Relapsed AML patients unable to undergo allogeneic HSCT,
- •6. Relapsed AML after allogeneic HSCT;
- •a. at least 100 days after transplant.
- •b. no evidence of active acute or chronic GvHD at enrolment, in case of history of acute (> overall grade 1) or chronic GvHD (moderate/severe) requiring immunosuppressive treatment no immunosuppression within the last 3 months,
- •c. no immunosuppression (with the exception of low-dose steroids =10 mg prednisone or equivalent) 4 weeks before enrollment and ongoing,
- •7. Myeloid blasts must positively express PRAME
- •Myelodysplastic Syndrome (MDS)-specific inclusion criteria:
- •1. International Prognostic Scoring System Intermediate-2 (IPSS INT-2) or High Grade MDS 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
- •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
排除标准
- •Key exclusion criteria include:
- •1. Subjects with acute promyelocytic leukemia exhibiting t(15;17)(q22;q12); Promyelocytic Leukemia/Retinoic Acid Receptor Alpha (PML-RARA), or with variant translocations
- •2. Pregnant or lactating women
- •3. Known positive for human immunodeficiency virus (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 subjects at special risk, such as:
- •a. Creatinine > 2.0 times the upper normal serum level
- •b. total bilirubin, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) > 3.0 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
- •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 National Cancer Institute’s (NCI) Common Terminology Criteria for Adverse Events (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
- •Treatment Exemption Criterion:
- •Unable to generate IMP for infusion; however, if a lower than planned number of cells is available (at least 1 x 105 T cells/kg), the subject in Phase I/II of the clinical trial will have the option to receive IMP and will be analyzed in the safety and full analysis set populations.
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