Clinical trial NCT03711864: Safety and Efficacy of IM21 Car-t Cells in Patients With Recurrent or Refractory BCMA Positive Multiple Myeloma
Official title: Safety and Efficacy of IM21 Car-t Cells in Patients With Recurrent or Refractory BCMA Positive Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Multiple Myeloma
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: Beijing Immunochina Medical Science & Technology Co., Ltd.
First posted: 2018-10-19
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In patients with multiple myeloma with recurrent or refractory BCMA, CAR-T cell infusion was performed after screening, blood collection and pretreatment. Starting dose for 5 x 10\^5 / kg, 1 x 10\^6 doses sequentially. If dose-limiting toxicity is not observed in 3 patients in a dose group, the next dose group test can be performed; If more than 2/3 of patients (2 cases, included) in a dose group had DLT, dose-escalation was not performed. If 1 case of DLT (1/3) appears in the first 3 patients of a dose group, 3 patients need to be added to the dose group (at this time, there are 6 patients in the group).

Detailed description: In patients with multiple myeloma with recurrent or refractory BCMA, CAR-T cell infusion was performed after screening, blood collection and pretreatment. Starting dose for 5 x 10\^5 / kg, 1 x 10\^6 doses sequentially. If dose-limiting toxicity is not observed in 3 patients in a dose group, the next dose group test can be performed; If more than 2/3 of patients (2 cases, included) in a dose group had DLT, dose-escalation was not performed. If 1 case of DLT (1/3) appears in the first 3 patients of a dose group, 3 patients need to be added to the dose group (at this time, there are 6 patients in the group). If DLT occurs in 1 of the 3 patients (with or without) or 2 of the 6 patients (with or without), no further dose escalation is allowed. Researchers and bidders to form drug safety monitoring committee (SRC), every dose group of subjects to complete the DLT observation period, after summarizing the security of this dose group, determine the test of the next dose, subjects such as draw up the highest dose group safety tolerance, SRC to decide whether to continue to increase the dose group of research, finally according to have obtained all the safety and efficacy of dose group information to determine the recommended dose (RP2D).Dose-limiting toxicity (DLT)

Eligibility criteria: Inclusion Criteria:

1. The patient had multiple myeloma (according to the updated IMWG diagnostic criteria)Active (symptomatic) myeloma
2. Refractory and recurrent multiple myeloma Refractory definition: 1) treated with at least second-line bortezomib or lenalidomide 2) determined by the clinician Definition of recurrence: refer to NCCN clinical guidelines for multiple myeloma (2016. V2), including recurrence after transplantation.
3. Age: 18 to 80 years old;
4. The expected survival time was more than 3 months;
5. ECoG score 0-2 (refer to Annex 2)
6. Hemoglobin (HB)≥80g/L; absolute neutrophil count (ANC)\>1×10\^9/L; platelet count(PLT)≥50×10\^9/L.

Those who voluntarily participated in the experiment and signed informed consent.

Exclusion Criteria:

1. High risk organ involvement patients: tumor invasion of central nervous system, gastrointestinal tract,lung,pericardium,one of the major vessels;
2. Those who have graft-versus-host reaction and need to use immunosuppressants, or who have autoimmune diseases;
3. Chemotherapy or radiotherapy was used within 3 days before blood collection;
4. Patients who used systemic steroids within 5 days before blood collection (except those who have recently or are currently using inhaled steroids);
5. The patients who used drugs to stimulate the production of bone marrow hematopoietic cells within 5 days before the blood collection period;
6. Those who have previously used any gene therapy products;
7. History of epilepsy or other central nervous system diseases;
8. New York Heart Association (NYHA) grade III or above (refer to Annex 3) (for patients with heart disease, this assessment is required);
9. Creatinine \> 1.5 times normal upper limit, ALT / AST\>3 times normal upper limit or bilirubin \>2 times normal upper limit;
10. Active hepatitis B or hepatitis C virus, HIV or other uncured active infections;
11. Pregnant or lactating women;
12. Those who suffer from other uncontrolled diseases are not suitable to join the study; Any situation that the researchers believe may increase the risk of subjects or interfere with the test results.

Primary outcomes:
measure: Occurrence of study related adverse events
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
affiliation: Peking Union Medical College Hospital
name: Daobin Zhou, M.D.
role: PRINCIPAL_INVESTIGATOR
References: