Anti-BCMA CAR-NK Cell Therapy for the Relapsed or Refractory Multiple Myeloma

NCT05008536 | Unknown Early Phase 1

• 1 other identifier: BCMA NK for MM
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to infuse BCMA CAR-NK cells（Umbilical \& Cord Blood (CB) Derived CAR-Engineered NK Cells） to the patients with relapsed and refractory multiple myeloma (MM), to assess the safety and feasibility of this strategy. The CAR enables the NK cells to recognize and kill the MM cells by targeting of BCMA, a protein expressed of the surface of the malignant plasma cells in MM patients.

Conditions

Multiple Myeloma, Refractory

Outcome Measures

Primary Outcomes (2)

• Overall Remission Rate (ORR)

  Response assessment per International Myeloma Working Group (IMWG) criteria

  2 monthes after infusion

• Incidence of dose limiting toxicity (DLTs)

  To characterize the safety, tolerability of Anti-BCMA CAR-NK Cells

  within 2 monthes after infusion

Secondary Outcomes (2)

• Progression-free survival (PFS)

  up to 24 months

• Duration of Response (DOR)

  up to 24 months

Study Arms (1)

Anti-BCMA CAR-NK Cells

EXPERIMENTAL

After preconditioning with chemotherapy, the Anti-BCMA CAR-NK Cells will be evaluated

Biological: Anti-BCMA CAR-NK Cells; Drug: Fludarabine; Drug: Cytoxan

Interventions

Anti-BCMA CAR-NK Cells BIOLOGICAL

1-3×10\^6 /KG, 3-6×10\^6 /KG, 0.6-1.2×10\^7/KG Treatment follows a lymphodepletion

Anti-BCMA CAR-NK Cells

Fludarabine DRUG

recommendation: 30mg/m2 (D-5\~D-3),determined by tumor burden at baseline.

Anti-BCMA CAR-NK Cells

Cytoxan DRUG

recommendation: 300-500mg/m2 (D-5\~D-3),determined by tumor burden at baseline.

Anti-BCMA CAR-NK Cells

Eligibility Criteria

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

You may qualify if:

• Signed written informed consent;
• According to the international standard for multiple myeloma，have information on medical examination proving the diagnosis of multiple myeloma.
• Received at least 2 prior lines of treatment, including proteasome inhibitor and immunomodulator, no efficacy more than PD; disease progression or relapsed after disease remission and refractory or no remission after treated in the last time.
• Measurable disease at screening as defined by any of the following: Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level veing as defined ；or light chain MM without measurable disease in the serum or the urine；serum immunoglobulin free light chain isease dL and abnormal serum immunoglobulin kappa/lambda free light chain ratio ；
• ECOG Scores: 0\~2（See Annex 3），the estimated survival time was more than 3 months;
• During the screening period, the clinical laboratory values met the following criteria： Hemoglobins70g/L (did not receive red blood cell transfusion ≤7 days prior to laboratory tests，recombinant human erythropoietin is allowed); Platelet count \>50×10\^9/L (did not receive blood transfusion ≤7 days prior to laboratory tests); Neutrophil absolute count oietin is (did not receive supportive treatment lowed); Platelet count \>50×10\^9/L，allowed to use over growth factor support); ALT and AST ≤3×ULN；Total bilirubin ≤2.0× UNL；Creatinine clearance×40mL/min；corrected serum calcium L/minctordL (3.1 mmol/L), or free calcium ion or freedL(L( ommol/L); Prothrombin time and activated partial thromboplastin time ≤1.5×ULN.
• The urine pregnancy test of female subjects of childbearing age should be negative and not in lactation;
• Females of childbearing potential and males must use efficient contraception（form signing the ICF to the end of the trial）

You may not qualify if:

• Have received CAR-NK therapy；
• Have a history of allergy to any component of cell products;
• Previous history of other malignancy;
• Any unstable cardiovascular disease happened the informed consent form by themselves or their legal guardian;boratory tests); be infused using the "3 + 3" dos grade), severe arrhythmia that require drug interference, cardiac angioplasty/coronary stent implantation/cardiac bypass surgery ≤6 months prior to enrollment;
• Have received allogeneic hematopoietic stem cell transplantation in 3 months for the treatment of multiple myeloma;
• who has suffered from brain injury, consciousness disorder, epilepsy, more serious cerebral ischemia or cerebral hemorrhage disease;
• There were live vaccinations within 4 weeks before admission;
• Active hepatitis (positive for HBVDNA or HCVRNA), syphilis and other acquired and congenital immunodeficiency diseases, including but not limited to those with HIV infection;
• Oxygen is needed to maintain adequate oxygen saturation;
• Contraindications for fludarabine or cyclophosphamide treatment.
• There was uncontrolled active infection;Patients with autoimmune diseases, immunodeficiency or other diseases requiring immunosuppressive （excluding glucocorticoid）therapy;
• Pregnant or breasting-feeding women;
• Subjects had a history of alcohol, drug or mental illness;
• Any other condition that researcher think it is inappropriate for the subject to anticipate the trial.

Sponsors & Collaborators

• Xinqiao Hospital of Chongqing: lead
• Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Department of Hematology, Xinqiao Hospital

Chongqing, Chongqing Municipality, 400037, China

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

fludarabine; Cyclophosphamide

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• xi zhang, PhD/MD

  Department of Hematology, Xinqiao Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

xi zhang, PhD/MD

CONTACT

13808310064; zhangxxi@sina.com

ruihao huang, MD

CONTACT

18984398751; 1169731117@qq.com

Study Design

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

Model Details: Anti-BCMA CAR-NK Cells

Study Record Dates

• First Submitted: August 14, 2021
• First Posted: August 17, 2021
• Study Start: October 1, 2021
• Primary Completion: September 1, 2022
• Study Completion: September 1, 2023
• Last Updated: November 23, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)