Relapsed/refractory acute myeloid leukemia
Conditions
Interventions
1:LCAR-L312
2:LCAR-LC12
Sponsors
Anhui Provincial Hospital
Eligibility
Sex/Gender
All
Age
14 Years to 60 Years
Inclusion criteria
Inclusion criteria: 1. Ability to understand and be willing to sign the informed consent form prior to any study procedures; 2. pathologically confirmed relapsed or refractory AML: (1) 2nd or greater Bone Marrow (BM) relapse; OR Refractory as defined by not achieving a CR after 2 cycles of a standard chemotherapy regimen ; OR relapse within 6 months after CR; or relapse later than 6-12 months after CR and didn't respond to the next induction regimen; (2) Eligible for allogeneic CBT; 3. To be aged 14~ 60 years; 4. Adequate organ function defined as: (1) Creatinine clearance was up to the related standard; (2) Alanine Aminotransferase (ALT) = 5 times the upper limit of normal (ULN)for age; (3) Bilirubin 95%; (5) Left Ventricular Ejection Fraction (LVEF) =45% confirmed by echocardiogram; 5. Bone marrow with = 5% myoblasts by morphologic assessment at screening; 6. Life expectancy > 12 weeks; 7. Karnofsky (age = 16 years) or Lansky (age < 16 years) performance status = 50 at screening.
Exclusion criteria
Exclusion criteria: 1. Isolated extra-medullary disease relapse. 2. Acute promyelocytic leukemia(APL M3): t(15,17) (q22;q12). 3. Patients with concomitant genetic syndrome: such as patients with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome. 4. Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease. 5. Treatment with any prior gene therapy product. 6. Has had treatment with any prior anti-CD33/anti-CLL1 therapy. 7. Treatment with any prior CAR-T. 8. Active or latent hepatitis B or active hepatitis C, or any uncontrolled infection at screening. 9. Human Immunodeficiency Virus (HIV) infection at screening. 10. The following medications are excluded: (1) Allogeneic cellular therapy: Any donor lymphocyte infusions (DLI) must be completed > 6 weeks prior to CD33/CLL-1-CAR-T and CLL-1-CAR-T infusion; (2) Chemotherapy: The following drugs must be stopped > 4 week prior to CD33/CLL-1-CAR-T and CLL-1-CAR-T infusion and should not be administered concomitantly or following lymphodepleting chemotherapy: Cytarabine 200 mg/m2/day Daunorubicin 60 mg/m2/day or idarubicin 12 mg/m2/day; (3) CNS disease prophylaxis:CNS prophylaxis treatment must be stopped > 1 week prior to CD33/CLL-1-CAR-T and CLL-1-CAR-T infusion (e.g. intrathecal methotrexate). 11. Active Central Nervous System (CNS) involvement by malignancy, defined as CNS-3 per National Comprehensive Cancer Network (NCCN) guidelines. Note: Patients with history of CNS disease that has been effectively treated will be eligible. Patient has received an investigational medicinal product within the last 30 days prior to screening. 12. Pregnant or nursing (lactating) women. NOTE: female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion. 13. Women of child-bearing potential (defined as all women physiologically capable of becoming pregnant) and all male participants, unless they are using highly effective methods of contraception for a period of 1 year after the CD33/CLL-1-CAR-T and CLL-1-CAR-T infusion. 14. With any history of active autoimmune disease or the disease. 15. Abnormal coagulation function. 16. With the history of unstable angina, symptomatic congestive heart failure or myocardial infarction in the past 6 months; 17. Severe uncontrolled arrhythmias;Left ventricular ejection fraction <45%. 18. Requiring parenteral antibiotics activity or uncontrolled infection;There is evidence of severe active viral, bacterial or uncontrolled systemic fungal infection; 19. chronic diseases treated with steroids or other immunosuppressive agents. 20. Hematopoietic growth factor was prophylactically used at the same time. 21. Concurrent use of anticancer drugs or therapies (including radiotherapy). 22. Those who have participated in clinical trials of other drugs. 23. Received surgery, radiotherapy, chemotherapy or other experimental treatment within 4 weeks before signing the ICF; 24. Stroke or convulsion occurred within 6 months prior to enrollment. 25. Live attenuated vaccine was administered within 4 weeks prior to single component blood collection. 26. Accepted major surgery within the 2 weeks before the single component blood collection, or book surgery plan during the study period or within 2 weeks after the study treatment is given.(note: subjects planning local anesthesia
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| AE;MTD; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacoketics;ORR;MRD; | — |
Countries
China
Contacts
Public ContactZheng Changcheng
Anhui Provincial Hospital
Outcome results
None listed