Safety and Efficacy of IM21 Car-t Cells in Patients With Recurrent or Refractory BCMA Positive Multiple Myeloma

Phase 1

• Conditions: Multiple Myeloma
• Interventions: Biological: IM21 CAR-T cells

• Registration Number: NCT03711864
• Lead Sponsor: Peking Union Medical College Hospital

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)

Study Timeline

• Study First Submitted: 2018-10-17
• Study First Submitted QC: 2018-10-17
• Study First Posted: 2018-10-19
• Study Start: 2019-02-25
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-28
• Last Update Posted: 2020-09-30
• Primary Completion: 2021-10-10
• Study Completion: 2021-12-20

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 15

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
IM21 CAR-T cells	IM21 CAR-T cells	IM21 CAR-T cells

Primary Outcome Measures

Name	Time	Method
Occurrence of study related adverse events	2 years	defined as \>= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment Adverse events assessed according to NCI-CTCAE v4.0 criteria 2.

Trial Locations

Locations (1)

Peking Union Medical College Hospital; 🇨🇳 Beijing, Beijing, China