Study of FasT CAR-T GC012F Injection in High Risk TE NDMM Patients

NCT04935580 | Unknown Phase 1

• 1 other identifier: GC012F-32
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, single-center, open-label clinical study to evaluate the safety and efficacy of GC012F in high-risk, transplant eligible patients with NDMM.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (5)

• Adverse Events (AE) after GC012F infusion

  An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), with the exception of cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). CRS and ICANS should be evaluated according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading

  Up to 1 year after patients infused with GC012F injection

• Overall response rate (ORR) as measured by International Myeloma Working Group (IMWG) criteria after GC012F infusion

  ORR defined as proportion of patients achieving PR or better based on IMWG defined response criteria

  Up to 2 years after patients infused with GC012F injection

• Percentage of patients with minimal residual disease (MRD) negative(tested by NGF at sensitivity of 10e-5 to 10e-4) at landmark analysis of 1/3/6/12/18/24 months post GC012F infusion

  MRD negative rate is defined as the proportion of participants who achieve MRD negative status by the respective time point

  Up to 2 years after patients infused with GC012F injection

• Progress free survival (PFS) at 6 months, 12 months and 24 months after GC012F infusion

  PFS defined as time from date of GC012F infusion to date of first documented disease progression, or death due to any cause, whichever occurs first. DOR defined as time form Month 1 after GC012F infusion to date of 1st documented PD if patients' response deeper or keeping sCR after CAR-T infusion.

  Up to 2 years after patients infused with GC012F injection

• Duration of response (DOR) at 6 months, 12 months and 24 months after GC012F infusion

  DOR defined as time form Month 1 after GC012F infusion to date of 1st documented PD if patients' response deeper or keeping sCR after CAR-T infusion.

  Up to 2 years after patients infused with GC012F injection

Secondary Outcomes (11)

• Overall survival (OS) after GC012F infusion

  Up to 2 years after patients infused with GC012F injection

• Time to first response (TTR) after GC012F infusion

  Up to 2 years after patients infused with GC012F injection

• Time to best response (TBR) after GC012F infusion

  Up to 2 years after patients infused with GC012F injection

• Change from Baseline in Health-related Quality of Life (HRQoL) as Measured by EORTC QLQ-C30

  Baseline up to study completion ( 2 years after GC012F Infusion on Day 0

• Change from Baseline in HRQoL as Measured by EORTC QLQ-MY20

  Baseline up to study completion ( 2 years after GC012F Infusion on Day 0

Study Arms (1)

GC012F treatment

EXPERIMENTAL

GC012F will be infused at a dose of1- 3 x 10\^5 CAR+ T cells/kg after receiving lymphodepleting chemotherapy. Lenalidomide maintenance therapy will be given post month 6 at physicians' choice.

Biological: GC012F injection

Interventions

GC012F injection BIOLOGICAL

GC012F injection is an autologous dual CAR-T targeted BCMA and CD19. A single infusion of CAR-T cells will be administered intravenously.

GC012F treatment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients should meet all of the following criteria:
• ≥18 years of age at the time of signing informed consent-upper age limit 70;
• High-risk defined as meet one or more of the following criteria at screen:
• R-ISS stage II or III;
• LDH \> the upper limit of normal;
• Meet one or more of cytogenetic high risk defined by: del 17p, t(4:14), t(14:16); Gain 1q21≥ 4 copies;
• Patients with extramedullary disease;
• IgD or IgE subtype;
• Meet one or more high-risk definition of mSMART3.0;
• Documented evidence of multiple myeloma at diagnosis as defined by IMWG guidelines CRAB (calcium elevation, renal insufficiency, anemia, and bone abnormalities)/SLiM criteria, monoclonal plasma cells in the bone marrow ≥10% or presence of a biopsy proven plasmacytomas, and measurable secretory disease according to IMWG criteria meet one or more of the following criteria at screening:
• Serum M protein ≥ 1 g/dL;
• Urine M protein ≥ 200 mg/24h;
• Serum free light chain sFLC ≥ 10 mg/dL with abnormal serum immunoglobulin κ/λ free light chain ratio.
• ECOG score was 0-2 at screen;
• Estimated life expectancy ≥3 months;

You may not qualify if:

• Patients should be excluded if they meet any one of the following criteria:
• Patients with purely non-secretory MM;
• Subject has had radiation therapy within 14 days of screening;
• Subjects has plasma cell leukemia or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes);
• Subjects has a diagnosis of primary amyloidosis, Waldenstroem's disease, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma;
• Having other tumors (excluding non-melanoma skin cancer and cervical cancer in situ bladder cancer and breast cancer that have been disease-free for more than 5 years);
• Overt clinical evidence of dementia or altered mental status; any history of central nervous system (CNS) disease or neurodegenerative disorder, such as epilepsy, seizures, paralysis, aphasia, stroke, severe brain damage, dementia, Parkinson's disease, psychosis;
• History of hereditary diseases such as Fanconi anemia, Schrader syndrome, Costerman syndrome, or any other known bone marrow failure syndrome;
• Clinically significant cardiac disease including: uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities, grade III-IV heart failure or myocardial infarction cardiac angioplasty or stenting unstable angina or other clinically significant cardiac conditions within one year prior to enrollment;
• Presence of any indwelling catheter or drainage tube (e.g., percutaneous nephrostomy catheter indwelling catheter bile drainage tube or pleural/peritoneal/pericardial catheter) permits the use of a dedicated central venous catheter;
• Subjects is exhibiting clinical signs of meningeal involvement of multiple myeloma;
• A positive virological result for any of the following: HIV, HCV, HBsAg, TPPA;
• Other severe viral or bacterial infections or uncontrolled systemic fungal infections are present;
• Subjects with a history of severe hypersensitivity;
• There is a history of an autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) that has resulted in terminal organ damage or requires systemic immunosuppressive/disease modulating drugs in the past 2 years;

Sponsors & Collaborators

• Shanghai Changzheng Hospital: lead
• Gracell Biotechnologies (Shanghai) Co., Ltd.: collaborator

Study Sites (1)

Shanghai Changzheng Hospital

Shanghai, Shanghai Municipality, 200003, China

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Juan Du, MD

  Shanghai Changzheng Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Juan Du, MD

CONTACT

+86-21-81885423; changzheng_pg@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Hematology Department

Study Record Dates

• First Submitted: June 13, 2021
• First Posted: June 23, 2021
• Study Start: June 28, 2021
• Primary Completion: July 1, 2023
• Study Completion: July 1, 2023
• Last Updated: August 3, 2022

Record last verified: 2022-08

Locations

CN (1)