EUCTR2018-000813-19-CZ进行中（未招募）1 期
A Phase I-IIa trial to assess the safety and antitumor activity of autologous CD44v6 CAR T-cells in acute myeloid leukemia and multiple myeloma expressing CD44v6.
MolMed S.p.A.0 个研究点目标入组 68 人开始时间: 2019年2月27日最近更新:
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 68
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
- •1. Written informed consent before any study-related procedure.
- •2. Adults and children:
- •a) Adults 18 to 75 years old with AML or MM
- •b) Children 1 to 17 years old with AML, only in Phase IIa
- •3. Confirmed diagnosis of AML or MM as follows:
- •a) AML: Primary or secondary AML (any subtype except acute promyelocytic leukemia) according to World Health Organization (WHO) classification
- •b) MM with measurable disease as defined by the International Myeloma Working Group (IMWG).
- •4. Patients with relapse or refractory disease:
- •a) AML patients must be unlikely to benefit from cytotoxic chemotherapy as follows:
- •Leukemia refractory to at least 2 induction attempts (use of a hypomethylating agent for at least 4 cycles can be considered a line of treatment).
- •Leukemia in relapse within 1 year following complete response (CR) after at least 2 induction attempts (use of a hypomethylating agent for at least 4 cycles can be considered a first line of treatment).
- •High-risk leukemia in adults according to 2017 European LeukemiaNet (ELN) in first relapse after a hypomethylating agent or a cycle containing cytarabine at a dose = 1g/sqm a day (e.g. FLAG-IDA), except for FLT3-mutated AML.
- •High-risk leukemia in children as defined by the Italian Association of Pediatric Hematology and Oncology (AIEOP).
- •b) Patients with MM must have a relapse or refractory disease after at least 4 different prior treatments in 3 treatment lines, or 4 treatments in 2 treatment lines in case of early relapsing patients (relapse in less than 1.5 years). Treatments include:
- •Proteasome inhibitor
- •High-dose alkylating agent if patient less than 70 years old
- •Immunomodulatory drug (IMID)
- •A monoclonal antibody (i.e. anti CD38 monoclonal antibody)??
- •5. Positive CD44v6 expression on tumor cells by flow cytometry.
- •6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- •7. Life expectancy of at least 12 weeks.
- •8. Adequate organ function:
- •a) Alanine aminotransferase (ALT) level within 2.5 times the institutional upper limit of normal (ULN).
- •b) aspartate aminotransferase (AST) level = 2.5 x ULN.
- •c) Total bilirubin level = 1.5 x ULN, or = 2.5 x ULN in case of history of Gilbert’s disease.?
- •d) Serum creatinine = 2.0 mg/dL or a calculated or measured creatinine clearance = 45mL/min.
- •e) Corrected Diffusing Capacity of Carbon Monoxide (DLCO) (via Dinakara Equation) or FEV1 of ? 66% without dyspnea on slight activity after hemoglobin correction.
- •f) Left ventricular ejection fraction ? 45%.
- •9. Recovery from toxicities of clinical consequence attributed to previous chemotherapy to CTCAE v5.0 Grade 1 (i.e., certain toxicities such as alopecia will not be considered in this category).
- •10. Ability to comply with study procedures, including hospitalization and protocol-specified acquisition of blood and/or bone marrow specimens.?
- •11. Willing to be followed up long-term (15 years) as required by health authorities for cell and gene therapy products
- •12. Women of childbearing potential must have test negative for pregnancy at enrolment and during the study and agree to use an effective method of contraception.
- •Are the trial subjects under 18? yes
- •Number of subjects for this age range: 7
- •F.1.2 Adults (18-64 years) yes
- •F.1.2.1 Number of subjects for this age range 58
- •F.1.3 Elderly (>=65 years) yes
- •F.1.3.1 Number of subjects for this age range 3
排除标准
- •1. History of or candidate for allogeneic stem cell transplantation.?
- •2. Cardiovascular, pulmonary, renal, and hepatic ?functions that in the judgment of the investigator are insufficient to undergo investigational CAR T-cell therapy.
- •3. Any history of or suspected current autoimmune disorders (apart from vitiligo, resolved childhood atopic dermatitis, Graves’ disease clinically controlled).
- •4. History of rheumatologic disorders requiring specific treatment at any time in the patient’s medical history.
- •5. Second primary malignancy that requires active therapy. Adjuvant hormonal therapy is allowed. ??
- •6. Known or suspected central nervous system (CNS) leukemia. ?
- •7. Presence or history of myeloid sarcoma or any extramedullary mass.
- •8. Any medical or psychiatric condition that may limit compliance or increase safety risks, such as:
- •a) Active uncontrolled infection (including, but not limited to viral, bacterial, fungal, or mycobacterial infection).?
- •b) Patients with known multiple antibiotic resistant infections in their clinical history.
- •c) Known human immunodeficiency virus infection, active or chronic hepatitis B or C infection. ?
- •d) Grade 3 or 4 bleeding. ??
- •e) Uncontrolled hypertension (systolic pressure > 180 mm Hg or diastolic pressure > 100 mm Hg). ?
- •f) Clinically significant arrhythmia, clinically significant baseline QTcF, or QTcF > 480 msec. ?
- •g) Unstable angina. ?
- •h) Myocardial infarction within 6 months prior to study drug administration. ?
- •i) Clinically significant heart disease (e.g. CHF NYHA III or IV, unstable coronary artery disease, myocardial infarction < 6 mo. prior to study entry).
- •j) Pregnancy or breast feeding.
- •k) Major surgery or trauma within 4 weeks before enrollment. ?
- •l) Dementia or altered mental status that would preclude sufficient understanding to provide informed consent.
- •Once all the above eligibility criteria are confirmed, a lymphocyte apheresis product of non-mobilized cells must be received and accepted by the manufacturing site. Note: the lymphocyte apheresis product will not be shipped or assessed for acceptance by the manufacturing site until documented confirmation of all other inclusion/exclusion criteria have been satisfied.
- •Prior to lymphocyte apheresis (week -9 to -7), the following criteria must be met:
- •1. Peripheral blast count = 20,000/mm3 (AML).
- •2. No treatment with any other investigational agent in the previous 4 weeks.
- •3. No treatment with an immunostimulatory agent (IMIDs are allowed) or any cell therapy in the previous 30 days.
- •4. Negative to the following tests: HCV (Antibody, NAT), HIV 1-2 (p24, AB, Ag and NAT), total Ig Treponema Pallidum (if positive perform specific test), Australia HBsAg, total anti HB core Ab (if positive perform HBV DNA NAT), mycoplasma (PCR or IgM) and HTLV I-II.
- •Prior to lymphodepleting chemotherapy and MLM-CAR44.1 T-cell infusion (day -5 to day -3), the following criteria must be met:
- •1. Evidence of active disease at the beginning of lympho-depleting chemotherapy.
- •2. The following medications are excluded and should not be administered concomitantly or following lymphodepleting chemotherapy:
- •a) Monoclonal antibodies in the 8 weeks prior to MLM-CAR44.1 T-cell infusion are prohibited.
- •b) Salvage chemotherapy (e.g. clofarabine, cytosine arabinoside > 100 mg/m2, anthracyclines, cyclophosphamide, proteasome inhibitors, IMIDs) must be stopped > 2 weeks prior to lymphodepleting chemotherapy
- •c) Granulocyte colony stimulati
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