BCMA and CD19 Targeted Fast Dual CAR-T for BCMA+ Refractory/Relapsed Multiple Myeloma

Exploratory Study to Evaluate Efficacy and Safety of GC012F Injection in BCMA+ Refractory/Relapsed Multiple Myeloma

This is a single arm, open-label, multi-center prospective study to determine the safety and efficacy of GC012F CAR-T cells in patients diagnosed with BCMA+ refractory/relapsed multiple myeloma (r/r MM).

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Biological: GC012F injection

Detailed Description

The main aim of the study is to determine the safety and efficacy of GC012F in r/r MM. GC012F is an autologous dual chimeric antigen receptor T-cell (CAR-T) therapy that targets B-cell maturation antigen (BCMA) and CD19. This study comprises of a Screening Phase (less than or equal to [<=] 28 days prior to apheresis) followed by Apheresis (will occur upon enrollment); Treatment Phase including a conditioning regimen followed by infusion of GC012F and post-infusion assessments from Day 1 to Day 84; and a Post-treatment Phase (Day 85 and up to end of the study). Efficacy will be explored to assessed and safety will be closely monitored during the study.

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

Contacts and Locations

• Study Contact: Name: Weijun Fu; Phone Number: (+86)13816052522; Email: fuweijun2010@hotmail.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Shanghai Changzheng Hospital
      • Contact: Weijun Fu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients must have a confirmed prior diagnosis of active multiple myeloma as defined by the updated IMWG criteria;

2. Diagnosis of MM with relapsed or refractory disease. Definition of Refractory/relapse:

   1. Have had at least 3 prior lines of therapy or primary refractory as defined by Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Prior therapy should include PI and IMiD. Note: Patients should undergone at least have at least complete 1 cycle treatment in each line. Induction with or without hematopoietic stem cell transplant followed by maintenance therapy is considered a single line of therapy.
   2. Have had at least 2 prior lines of therapy when refractory to both immunomodulatory drug (IMiD) and proteasome inhibitor(PI) (Refractory was defined by IMWG consensus criteria);
3. Estimated life expectancy ≥3 months;
4. Hemoglobin ≥ 8.0 g/dL;
5. Absolute neutrophil count ≥ 0.75*10E9/L;
6. Platelet count ≥ 50*10E9/L;
7. Absolute lymphocyte count ≥ 1*10E8/L;
8. Liver, kidney and cardiopulmonary functions meet the following requirements: a)Total bilirubin ≤ 2×ULN(except for Gilbert Syndrome); ALT and/or AST ≤3 × ULN; b)clearance of serum creatinine ≥ 40 mL/min, calculated by Cockcroft-Gault; c)Corrected serum calcium ≤ 12.5mg/dL or free ion calcium ≤ 6.5mg/dL(1.6mmol/L);
9. Sufficient venous access for leukapheresis collection, and no other contraindications to leukapheresis;
10. Subjects and sexual partner with fertility are willing to use effective and reliable method of contraception for at least 100 days after CART cell infusion;
11. Subjects must have signed written, informed consent.

Exclusion Criteria:

1. Accompanied by other uncontrolled malignancies.There are two exceptions to this criterion: Recepted radical therapy carcinoma without activity within 3 years before screening; and fully treated skin non-melanoma;
2. Any situations not benefit for subjects to accept or tolerated to planned therapy or understand informed consent; or any situation in which investigators believe that participation in this study is not in the subject's best interests (e.g., harm to health), or any situation that may prevent, limit or confuse the assessment;
3. Convulsion or stoke within past 6 months;
4. Any instability of systemic disease within 6 months prior to screening, including but not limited to congestive heart failure (New York heart association (NYHA) classification ≥ III), unstable angina, cerebrovascular accident, or transient cerebral ischemic, myocardial infarction,LEVF< 45% (assessed by an echocardiogram or multi-door circuit scan );
5. Patients have central nervous system (CNS) metastases or CNS involvement (including cranial neuropathies or mass lesions and leptomeningeal disease);
6. Subjects with positive HBsAg or HBcAb postive and peripheral blood HBV DNA titer is higher than the lower limit of detection of the research institution; HCV antibody positive; HIV antibody positive; syphilis primary screening antibody positive;
7. Presence or suspicion of fungi, bacteria, viruses or other infections that are uncontrollable or requiring intravenous treatment;
8. Activity of autoimmune diseases (such as crohn's disease, rheumatoid arthritis, systemic lupus erythematosus), orhistory of autoimmune disease within the last 3 years;
9. Clinical evidence of dementia or changes of mental state.
10. Exist of pulmonary fibrosis;
11. Allergy subjects or history of severe hypersensitivity;
12. Oxygen inhalation requirment to maintain adequate oxygen saturation;
13. Surgery (except for local anesthesia surgery) plan 2 weeks before apheresis. during or 2 weeks after CART infusion;
14. Chemotherapy forbidden for cyclophosphamide or fludarabine;
15. Pregnant or lactating, or planning to have a pregnancy during or within 100 days after treatment;
16. Patients who are accounted to be not appropriate for this trail by investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: GC012F treatment; BCMA+ R/R multiple myeloma patients be treated with a single dose of GC012F cells. Total dose of (1-5)*10E5/kg cells will be administered at Day 0.	Biological: GC012F injection; GC012F injection is a autologous dual CAR-T targeted BCMA and CD19. A single infusion of CART cells will be administered intravenously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence and severity of adverse events after GC012F infusion	up to 24 weeks after GC012F infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of MRD negative patients after GC012F treatment		12 weeks, 24 weeks after GC012F infusion
ORR (PR, VGPR, CR and sCR) of patients receive GC012F treatment		12 weeks, 24 weeks after GC012F infusion
Progression free survival after GC012F treatment		12 weeks, 24 weeks after GC012F infusion
Copies and cell counts of CAR in blood and bone marrow (if available) after GC012F treatment	Bone marrows will be collected in weeks 4, 8, 12, 18, 24 after GC012F infusion.	Days 4, 7, 10, 14 and weeks 4, 8, 12, 18, 24 after GC012F infusion
Cytokines in serum after GC012F treatment		Days 4, 7, 10, 14 and weeks 4, 8, 12, 18, 24 after GC012F infusion
Subset of lymphocytes and ADA in blood after GC012F treatment		Weeks 4, 8, 12, 18, 24 after GC012F infusion
Replication competent lentivirus (RCL) in blood after GC012F treatment		Weeks 4, 12, 24 after GC012F infusion
Duration of response after GC012F treatment		12 weeks, 24 weeks after GC012F infusion
Overall survival after GC012F treatment		12 weeks, 24 weeks after GC012F infusion

Collaborators and Investigators

• Sponsor: Shanghai Changzheng Hospital
• Collaborators: Gracell Biotechnology Shanghai Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 16, 2020
• Primary Completion (ANTICIPATED): July 31, 2022
• Study Completion (ANTICIPATED): December 31, 2022

Study Registration Dates

• First Submitted: January 15, 2020
• First Submitted That Met QC Criteria: January 18, 2020
• First Posted (ACTUAL): January 22, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 15, 2021
• Last Update Submitted That Met QC Criteria: June 13, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Multiple Myeloma; CD19; BCMA; Fast; Chimeric Antigen Receptor T
• 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: GBF002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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