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

Phase I Study to Evaluate the Safety and Effectiveness of Anti-BCMA CAR-NK Therapy in Relapsed or Refractory Multiple Myeloma

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.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma, Refractory
• Intervention / Treatment: Drug: Fludarabine; Drug: Cytoxan; Biological: Anti-BCMA CAR-NK Cells

• Study Type: Interventional
• Enrollment (Anticipated): 27
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: xi zhang, PhD/MD; Phone Number: +86 13808310064; Email: zhangxxi@sina.com
• Study Contact Backup: Name: Ruihao Huang, MD; Phone Number: +86 18984398751; Email: 1169731117@qq.com

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400037
      • Recruiting
      • Department of Hematology, Xinqiao Hospital
      • Contact: Ruihao Huang, MD; Phone Number: +86 18984398751; Email: 1169731117@qq.com
      • Contact: Xi Zhang, MD/PhD; Phone Number: +86 13808310064; Email: zhangxxi@sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed written informed consent;
2. According to the international standard for multiple myeloma，have information on medical examination proving the diagnosis of multiple myeloma.
3. 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.
4. 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 ；
5. ECOG Scores: 0~2（See Annex 3），the estimated survival time was more than 3 months;
6. 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.
7. The urine pregnancy test of female subjects of childbearing age should be negative and not in lactation;
8. Females of childbearing potential and males must use efficient contraception（form signing the ICF to the end of the trial）

Exclusion Criteria:

1. Have received CAR-NK therapy；
2. Have a history of allergy to any component of cell products;
3. Previous history of other malignancy;
4. 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;
5. Have received allogeneic hematopoietic stem cell transplantation in 3 months for the treatment of multiple myeloma;
6. who has suffered from brain injury, consciousness disorder, epilepsy, more serious cerebral ischemia or cerebral hemorrhage disease;
7. There were live vaccinations within 4 weeks before admission;
8. Active hepatitis (positive for HBVDNA or HCVRNA), syphilis and other acquired and congenital immunodeficiency diseases, including but not limited to those with HIV infection;
9. Oxygen is needed to maintain adequate oxygen saturation;
10. Contraindications for fludarabine or cyclophosphamide treatment.
11. There was uncontrolled active infection;Patients with autoimmune diseases, immunodeficiency or other diseases requiring immunosuppressive （excluding glucocorticoid）therapy;
12. Pregnant or breasting-feeding women;
13. Subjects had a history of alcohol, drug or mental illness;
14. Any other condition that researcher think it is inappropriate for the subject to anticipate the trial.

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: Anti-BCMA CAR-NK Cells; After preconditioning with chemotherapy, the Anti-BCMA CAR-NK Cells will be evaluated	Drug: Fludarabine; recommendation: 30mg/m2 (D-5~D-3),determined by tumor burden at baseline.; Drug: Cytoxan; recommendation: 300-500mg/m2 (D-5~D-3),determined by tumor burden at baseline.; Biological: Anti-BCMA CAR-NK Cells; 1-3×10^6 /KG, 3-6×10^6 /KG, 0.6-1.2×10^7/KG Treatment follows a lymphodepletion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Response assessment per International Myeloma Working Group (IMWG) criteria	up to 24 months
Duration of Response (DOR)	Response assessment per International Myeloma Working Group (IMWG) criteria	up to 24 months

Collaborators and Investigators

• Sponsor: Xinqiao Hospital of Chongqing
• Collaborators: Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.
• Investigators: Principal Investigator: xi zhang, PhD/MD, Department of Hematology, Xinqiao Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2021
• Primary Completion (Anticipated): September 1, 2022
• Study Completion (Anticipated): September 1, 2023

Study Registration Dates

• First Submitted: August 14, 2021
• First Submitted That Met QC Criteria: August 14, 2021
• First Posted (Actual): August 17, 2021

Study Record Updates

• Last Update Posted (Actual): November 23, 2021
• Last Update Submitted That Met QC Criteria: November 21, 2021
• Last Verified: November 1, 2021

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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine
• Other Study ID Numbers: BCMA NK for MM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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