B Cell Maturation Antigen（BMCA）-Targeted CAR-T for Refractory/Relapsed Multiple Myeloma

• ClinicalTrials.gov Identifier: NCT03931421
• Recruitment Status: Recruiting
• First Posted: April 30, 2019
• Last Update Posted: June 4, 2019
• Sponsor: First Affiliated Hospital of Zhejiang University
• Information provided by (Responsible Party): Wenbin Qian, First Affiliated Hospital of Zhejiang University

Study Description

Brief Summary:

It's a single arm, open label prospective study, in which the safety and efficacy of B Cell Maturation Antigen（BMCA）-targeted CAR-T thearpy are evaluated in refractory/relapsed multiple myeloma patients.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma	Biological: CAR-T treatment	Phase 2

Detailed Description:

In this trial, T cells are seperated from multiple myeloma patients, and engineered into BMCA-targeted CAR-T cells, these cells are then transfused back into the patients to elimimnate the myeloma cells. In this process, the safety and efficacy of this CAR-T treatment are closely monitored.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: In this trial, T cells were seperated from refractory/relapsed multiple myeloma patients and engineered into BMCA-targeted CAR-T cells, and then transfused back into the patients for the treatment of their multiple myeloma.
• Masking: None (Open Label)
• Masking Description: It's an open-label trial.
• Primary Purpose: Treatment
• Official Title: B Cell Maturation Antigen（BMCA）-Targeted CAR-T for Refractory/Relapsed Multiple Myeloma
• Estimated Study Start Date: July 31, 2019
• Estimated Primary Completion Date: November 30, 2022
• Estimated Study Completion Date: December 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: experiment group; In this arm, patients are treated with B Cell Maturation Antigen (BMCA)-targeted CAR-T cells and the safety and efficacy will be observed.	Biological: CAR-T treatment; a novel method for treatment of multiple myeloma, in which patients' T cells are engineered into B Cell Maturation Antigen（BMCA）-Targeted CAR-T cells to eliminate myeloma cells.

Outcome Measures

Primary Outcome Measures :

1. complete remission rate [ Time Frame: at the time point 3 months after CAR-T cell transfusion ]
   complete remission rate after treated by CAR-T therapy
2. incidence and severity of adverse events [ Time Frame: from the date of the start of treatment to 36 months after last patient's enrollment ]

   any unfavorable and unintended sign , symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure

   any unfavorable and unintended sign , symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure

   any unfavorable and unintended sign , symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure

Secondary Outcome Measures :

1. progression free survival [ Time Frame: from the day of treatment to the date of first documented progression，up to 36 months after the last patient's enrollment ]
   from date of inclusion to date of progression, relapse, or death from any cause
2. overall survival [ Time Frame: from the day of treatment to the date of first documented progression，up to 36 months after the last patient's enrollment ]
   from the date of inclusion to date of death, irrespective of cause
3. duration of the CAR-T cells in the patients [ Time Frame: from the date of re-transfusison to 36 months after last patient's enrollment ]
   time from re-transfusion to date when the modified T cells become non-detectable

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 1. Age≥18，male or female;
• 2. ECOG 0-3;
• 3. Clearly diagnosed as multiple myeloma (MM) [according to IMWG 2014 criteria];
• 4. Patients should have received 3 different regimens prior to enrollment (each regimen should last for at least one complete cycle, except for the case of disease progression);
• 5. Previously received one PI and IMiD treatment;
• 6. MM patients should fit one of the following: 1) disease progression; 2) relapsed after CR. The corresponding criteria is defined as follows: a, disease progression should satisfy at least 1 of the following: serum M protein ≥0.5g/dl, or urine M protein>200mg/24h, or FLC increasement >10mg/dl, or bone marrow plasma cell proportion >10%, or with new bone disease/plasmacytoma/original focus increased by 50% or more, or hypercalcemia ( corrected serum calcium level >11.5mg/dL(2.65mmol/L); b. relapse after CR, should satisfy one of the following: ①M protein in urine or blood; ②bone marrow plasma cell proportion≥5%; ③manifestation of disease progression, such as plasmacytoma, osteolytic lesions or hypercalcemia.
• 7. Peripheral blood mononucleated cell separation should be at least 2 weeks from chemo/radiotherapy;
• 8. Neutrophil count≥1000/ul, platelet count≥45000/ul, Hb>60g/l;
• 9. Cardiac, hepatic and renal function: Creatinin <1.5 times of normal maximum；ALT/AST level <2.5 times of the maximum of normal range; total bilirubin<1.5 times of ULN；cardiac ejection fraction≥ 50%; no pericardial effusion within 6 weeks prior to enrollment;
• 10. Being able to understand and willing to sign the written consent;
• 11. Fertile patients should agree to take contraceptive measures during the process of this trial.

Exclusion Criteria:

• 1. History of other tumors other than multiple myeloma, except for the following: malignant tumor after radical surgery, and have been inactive for ≥3 years prior to enrollment; skin cancer (not melanoma) after sufficient treatment, no evidence of disease at enrollment;
• 2. History of the following treatment: received targeted therapy, epigenetic therapy or clinical trials, invasive operation within 14 days/5 half-time prior to enrollment. History of monoclonal antibody within 21 days prior to enrollment. History of cytotoxic medicine or proteasome treatment within 14 days prior to enrollment. History of immunomodulatory treatment within 7 days prior to enrollment;
• 3. History of >5mg/d systemic prednisone treatment (or other glucocorticoids of the equivalent dosage) within 2 weeks prior to peripheral mononucleated cell collection;
• 4. With CNS involvement or clinical manifestation of meningeal myeloma;
• 5. With active systemic infection;
• 6. With active HBV infection or HCV infection, or history of type C hepatitis;
• 7. With immunodeficiency, including HIV infection;
• 8. With the following heart condition: NYHA level III or IV congestive heart failure; myocardial infarction or CABG within 6 months prior to enrollment; clinically meaningful ventricular arrythmia, or history of idiopathic syncope (not caused by vascular-vagal disorder or dehydration), history of non-ischemic myopathy;
• 9. With active autoimmune disease;
• 10. History of autologous stem cell transplantation within 6 weeks prior to enrollment;
• 11. History of allogenic stem cell transplantation.

Contacts and Locations

Contacts

Contact: Wenbin Qian, MD,PhD; (+86)13605801032; qianwenb@aliyun.com

Contact: Hui Liu, MD,PhD; (+86)13819198629

Locations

China, Zhejiang

The first affiliated hospital of Zhejiang University; Recruiting

Hangzhou, Zhejiang, China, 310000

Contact: Wenbin Qian, MD,PhD (+86)13605801032 qianwenb@aliyun.com

Sponsors and Collaborators

First Affiliated Hospital of Zhejiang University

More Information

• Responsible Party: Wenbin Qian, clinical professor, First Affiliated Hospital of Zhejiang University
• ClinicalTrials.gov Identifier: NCT03931421
• Other Study ID Numbers: lymphoma center Q004
• First Posted: April 30, 2019
• Last Update Posted: June 4, 2019
• Last Verified: June 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: All the data would be available on the website of the affiliated hospital after the trial is completed
• Supporting Materials: Study Protocol; Clinical Study Report (CSR)

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

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