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

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).

Study Overview

• Status: Unknown
• Conditions: Multiple Myeloma
• Intervention / Treatment: Biological: IM21 CAR-T cells

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 Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100005
      • Recruiting
      • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IM21 CAR-T cells	Biological: IM21 CAR-T cells; fludarabine and cyclophosphamide Two days before cell infusion,all patients will be treated with fludarabine and cyclophosphamide for 3 days; Other Names: IM21

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of study related adverse events	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.	2 years

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: Beijing Immunochina Medical Science & Technology Co., Ltd.
• Investigators: Principal Investigator: Daobin Zhou, M.D., Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2019
• Primary Completion (Anticipated): October 10, 2021
• Study Completion (Anticipated): December 20, 2021

Study Registration Dates

• First Submitted: October 17, 2018
• First Submitted That Met QC Criteria: October 17, 2018
• First Posted (Actual): October 19, 2018

Study Record Updates

• Last Update Posted (Actual): September 30, 2020
• Last Update Submitted That Met QC Criteria: September 28, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: YMCART201804

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No