NIPH Clinical Trials Search

JAPANESE
国立保健医療科学院
JRCT ID: jRCT2033210029

Registered date:09/04/2021

Investigator-initiated, first-in-human trial of non-virally engineered GMR CAR T cells against CD116-positive acute myeloid leukemia and juvenile myelomonocytic leukemia.

Basic Information

Recruitment status Recruiting
Health condition(s) or Problem(s) studiedCD116-positive acute myeloid leukemia and juvenile myelomonocytic leukemia
Date of first enrollment22/03/2021
Target sample size18
Countries of recruitmentJapan
Study typeInterventional
Intervention(s)Administration of CAR-T cells produced from eripheral blood

Outcome(s)

Primary OutcomeSafety and adverse effects of GMR CAR-T therapy by day 56 after GMR CAR-T infusion or by the time of bridgingallogeneic hematopoietic stem cell transplantation.
Secondary Outcome(1) Complete remission rate (CR + CRi) 28 days after GMR CAR-T infusion. (2) Cytogenetic and molecular response rates (if the patients have detectable cytogenetic and /or molecular minimal residual disease). (3) Hematopoietic stem cell transplantation (HSCT) rate. (4) Phenotypic analysis of GMR CAR-T cells. (5) Pharmacokinetics of GMR CAR-T cells. (6) Manufacturing success rate for GMR CAR-T cells.

Key inclusion & exclusion criteria

Age minimum>= 1age old
Age maximumNot applicable
GenderBoth
Include criteria1.Subjects with CD116 positive myeloid malignancies who relapsed after HSCT or experienced induction failure. 2.Aged >=18 years in cohort 1 and >= 1 year in cohorts 2 and 3 at the time of study entry. 3.PS score (Age >= 16 years) >= 50 persent or Lansky score (Age < 15 years) >= 50 persent. 4.HSCT donors are available within 56 days after GMR CAR-T infusion. 5.Subjects capable of undergoing leukapheresis. 6.Adequate normal organ and tolerable disease control defined below. a. WBC count <= 50,000 /micro-L b. Absolute lymphocyte count >= 500/micro-L or CD3 positive T cells >= 150/micro-L. c. Serum bilirubin <= 2.0 mg/dL. d. AST <= 5-fold the upper limit of normal for age. e. ALT <= 5-fold the upper limit of normal for age. f. Serum creatinine <= 2.0 mg/dL. g. SpO2 >= 95% (room air) 7.Left ventricular ejection fraction (EF) >= 50 persent, no pericardial effusion, and no abnormal electrocardiography findings requiring treatment. 8.Life expectancy >= 3 months. 9.Written informed consent can be obtained from patients and/or representatives.
Exclude criteria1.Subjects with prior or concurrent malignancies other than myeloid malignancies. 2.Subjects with poor disease control such as increasing leukemia cell counts in peripheral blood. 3.Subjects who received other CAR-T therapy within 24 weeks. 4.Acute promyelocytic leukemia (APL ; FAB M3). 5.Subjects with the active central nervous system and/or extramedullary disease. 6.Subjects with acute graft-versus-host disease (GVHD) (Grade >= 2) or extensive chronic GVHD. Extensive chronic GVHD is either of either generalized skin involvement (>= 50 persent), localized skin involvement in the association with eye and/or oral involvement, abnormal liver histology (chronic progressive hepatitis, bridging necrosis, or cirrhosis), or other target organ involvement. 7.History of coronary heart disease, acute brain ischemia, or cerebral hemorrhage, or any sequelae of stroke such as paralysis. 8.Poorly controlled high blood pressure (systolic blood pressure > 160 mmHg, diastolic blood pressure > 100 mmHg). 9.Subjects with uncontrollable and/or severe infections. 10.History of pulmonary fibrosis and/or interstitial pneumonia or radiological findings indicating the presence of pulmonary fibrosis and/or interstitial pneumonia. 11.Subjects with poorly controlled diarrhea and/or diabetes mellitus. 12.Subjects with poorly controlled severe heart diseases such as congestive heart failure and arrhythmia, acute brain ischemia, or cerebral hemorrhage. Heart failure is defined as class 3 or 4 cardiovascular disability according to New York Heart Association functional classification. 13.Subjects with severe organ complications such as renal failure, liver failure, or ileus. 14.Subjects who have psychological disorders affecting the participation in the trial. 15.HIV infection and/or HTLV-1 infection. 16.Positive for HBs antigen or HBc antigen and HBV-DNA. 17.Active hepatitis C infection. 18.Prior treatment with any investigational drugs within 30 days prior to enrollment. 19.Prior treatment with any investigational cell and gene therapies within 6 weeks prior to enrollment. 20.Subjects concurrently receiving the following treatments. a. Corticosteroid (>= 6mg/m2/day equivalent prednisolone dose) b. Donor lymphocyte infusion within 6 weeks prior to the enrollment c. Treatment for GVHD (eg, calcineurin inhibitors, methotrexate, mycophenolate mofetil, TNF inhibitors, and IL-6 inhibitors) d. Salvage chemotherapy must be completed by the time of second registration 21.Females who are pregnant and/or breastfeeding 22.Females of child-bearing potential who are not willing to practice highly effective methods of birth control from the time of consent through more than 12 months after GMR CAR-T cells and after confirmation of two consecutive negative test results of CAR-T in peripheral blood by qPCR. Male subjects with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception from the time of consent to through more than 12 months after GMR CAR-T cells and after confirmation of two consecutive negative test results of CAR-T in peripheral blood by qPCR. As CAR-T cells can be transmitted through the sperm containing white blood cells, male subjects who underwent vasectomy must also practice sexual abstinence (refrain from heterosexual intercourse) or use contraception. Female subjects with no child-bearing potential (Age < 11 years old, amenorrhea for more than 24 months, hysterectomy, bilateral salpingectomy, and/or bilateral oophorectomy) can be enrolled even if they are unwilling to practice sexual abstinence. Female subjects who are becoming capable of pregnant during the study period must practice highly effective methods of birth control from the time of consent through more than 12 months after GMR CAR-T cells and after confirmation of two consecutive negative test results of CAR-T in peripheral blood by qPCR. 23.Subjects who are not inappropriate to participate in this study for any reason by the judgement of investigators.

Related Information

Contact

Public contact
Name Shoji Saito
Address 3-1-1 Asahi, Matsumoto, Nagano Nagano Japan 390-8621
Telephone +81-263-37-2642
E-mail shojis@shinshu-u.ac.jp
Affiliation Shinshu University Hospital
Scientific contact
Name Yozo Nakazawa
Address 3-1-1 Asahi, Matsumoto, Nagano Nagano Japan 390-8621
Telephone +81-263-37-2642
E-mail yxnakaza@shinshu-u.ac.jp
Affiliation Shinshu University Hospital