Clinical trial NCT03975907: Clinical Trial to Evaluate CT053 in Patients With Relapsed and/or Refractory Multiple Myeloma (LUMMICAR STUDY 1)
Official title: Open Label, Phase I/II Clinical Trial to Evaluate the Safety and Efficacy of Fully Human Anti-BCMA Chimeric Antibody Receptor Autologous T Cell （CAR T）in Patients With Relapsed and/or Refractory Multiple Myeloma (LUMMICAR STUDY 1)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: multiple myeloma
car-T
Lead sponsor: CARsgen Therapeutics Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Beijing Chao Yang Hospital
name: The First Affiliated Hospital of Soochow University
name: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
name: Tianjin Medical University General Hospital
name: First Affiliated Hospital of Zhejiang University
name: Beijing Hospital
name: Shanghai Tongji Hospital, Tongji University School of Medicine
name: First Affiliated Hospital of Wenzhou Medical University
name: Xiangya Hospital of Central South University
name: Peking University People's Hospital
name: Qilu Hospital of Shandong University
name: Sun Yat-sen University
name: First Affiliated Hospital, Sun Yat-Sen University
First posted: 2019-06-05
Enrollment: 121
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Phase I is an open-label, dose escalation study and 2 cohorts to evaluate the safety and tolerability of treatment with CT053 and to determine maximum tolerable dose (MTD) and the Recommended Phase 2 Dose (RP2D) for CT053.

Phase 2 is a single-arm, open, multi-center study, to evaluate the efficacy and safety of CAR-BCMA T cells (CT053) in subjects with RR/MM.
Primary purpose: TREATMENT

Brief summary: This is an open-label, single arm study to evaluate the safety and tolerability of treatment with CT053 CAR-BCMA T in patients with relapsed and/or refractory multiple myeloma.

Detailed description: The study is composed of two stages, Phase I stage is for dose escalation and recommendation of phase 2 dose, and Phase II stage is to Detailed Description: verify the efficacy and safety of the dose proposed.

Eligibility criteria: Inclusion Criteria:

1. Patients and legally acceptable representative must have voluntarily signed ICF and willing to complete the study procedure, after fully understanding of the study.
2. Age ≥ 18 years and ≤ 75 years, male or female
3. The patients have received at least 3 prior lines for MM, (Induction therapy followed by autologous transplantation\[ASCT\] and maintenance therapy represents one line of therapy, those who have not been treated with ASCT should have documented rationale); For each line of therapy, the patient should have received at least one standard treatment cycle (2016 IMWG) unless the best response to the treatment line is documented as progressive diseases (PD)
4. The patients should have received treatment with at least one proteasome inhibitor AND one immunomodulatory drug, and have ever been relapsed or deteriorated after treatment with at least one regimen consisting of above-mentioned medications (combination or single use)；
5. Patient should be relapsed within 12 months after the last line of therapy, or disease progressed within 60 days after last line of therapy (IMWG criteria 2016), with documented evidence.
6. The patients should have measurable disease based on at least one of the following parameters：

   * Serum M-protein ≥ 10 g/L;
   * Urine M-protein ≥ 200 mg/24 hrs;
   * For those whose Serum or Urine M- protein dose not meed the measurable criteria but the light chain type, serum free light chain (FLC): involved FLC level ≥ 10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal
7. Estimated life expectancy \> 12 weeks
8. ECOG performance score 0-1；
9. Sufficient venous access for leukapheresis collection, and no other contraindications to leukapheresis
10. Patients should maintain adequate organ function
11. Women of childbearing age must undergo a serum pregnancy test with negative results before screening and lymphodepletion preconditioning with fludarabine and cyclophosphamide, and are willing to use effective and reliable method of contraception for at least 1 year after T cell infusion
12. Men who actively have intercourse with child-bearing potential women must be willing to use effective and reliable method of contraception for at least 1 year after T cell infusion

Exclusion Criteria:

1. Pregnant or lactating women；
2. Positive for any following tests: human immunodeficiency virus (HIV) antibody, Treponema Pallidum antibody, hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg), HBV e antigen (HBeAg), HBV e antibody, hepatitis B core antibody, HBV DNA;
3. Patients with any uncontrolled active infection including but not limited to active tuberculosis.
4. Patients with AEs from previous treatment that have not recovered to Common Terminology Criteria for Adverse Events (CTCAE) ≤ 1, excluding hair loss, neuropathy and other events that the treating physician can determine to be tolerable.
5. Patients who have ever had any CAR T cell therapy；
6. Patients who have ever had anti-BCMA therapy；
7. Patients have received allogeneic stem cell transplantation for treating multiple myeloma;
8. Patients have received autologous stem cell transplantation less than 12 weeks before leukapheresis；
9. Patients have received any anti-cancer treatment within 14 days before leukapheresis including but not limited to cytotoxic therapy, proteasome inhibitors, immunomodulatory agents, targeted therapies, epigenetic therapy or experimental drug therapy. If the field of radiation covers ≤ 5% of the bone marrow, the subjects are eligible to participate in the study regardless of the radiotherapy end date；
10. Patients have received ≥ 5 mg prednisone daily or other equivalent dose of steroids within 14 days before leukapheresis or lymphodepletion；
11. Patients have plasma cell leukemia, Waldenström macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome or AL amyloidosis；
12. Patients have been administered live attenuated vaccine 4 weeks before leukapheresis or lymphodepletion
13. Patients allergic to component of study treatment.
14. Patients have any of the condition as following within 6 months of ICF sign-off: New York Heart Association (NYHA) stage III or IV congestive heart failure, angina pectoris, myocardial infarction, coronary artery bypass graft, stroke (excluding lacunar stroke), history of clinically significant arrhythmia including but not limited to ventricular arrhythmia, significant QT interval prolongation, uncontrolled blood pressure as defined as systolic \> 160 mmHg, diastolic \> 100 mmHg, uncontrolled diabetes mellitus, pulmonary thrombolism, other conditions that investigators believe that participating in this clinical trial may endanger the health of the patients
15. Patients are known to have active autoimmune diseases including but not limited to psoriasis, rheumatoid arthritis and other needs of long-term immunosuppressive therapy
16. patients are oxygen dependent as defined by the blood oxygen saturation (finger oxygen detection method) can be maintained \> 95% only by oxygen inhalation before leukapheresis
17. Patients with second malignancies in addition to MM are not eligible if the second malignancy has required treatment within the past 5 years or is not in complete remission. There are two exceptions to this criterion: successfully treated cervical carcinoma in situ and non-metastatic basal cell skin carcinoma
18. Patients have central nervous system (CNS) metastases or CNS involvement (including cranial neuropathies or mass lesions and leptomeningeal disease). Patients with history of spinal cord compression from MM are eligible provided spinal cord compression has been treated with surgery or radiation at least 28 days prior to study entry
19. Patients are unable or unwilling to comply with the requirements of clinical trial
20. Patients have received major surgery 2 weeks prior to leukapheresis or 4 weeks prior to lymphodepletion and after the study treatment (excluding cataract and other local anesthesia)
21. Patients are relatives to investigator or his/her staff, or those who may have an interest in the investigator and/or his/her staff.

Primary outcomes:
measure: Phase 1, Safety and tolerability: dose limiting toxicity
timeFrame: 28days post administration of CAR-T-cells
measure: Phase 2, efficacy of CT053 CAR-BCMA T cells: overall response rate
timeFrame: 3 months post administration of CAR-T-cells
Secondary outcomes:
measure: Additional efficacy evaluation after 12 weeks of CT053 CAR-BCMA T cells infusion
timeFrame: 3 months post administration of CAR-T-cells
measure: Additional efficacy evaluation after 12 weeks of CT053 CAR-BCMA T cells infusion
timeFrame: 3 months post administration of CAR-T-cells
measure: Additional efficacy evaluation after 12 weeks of CT053 CAR-BCMA T cells infusion
timeFrame: 3 months post administration of CAR-T-cells
measure: Additional efficacy evaluation after 12 weeks of CT053 CAR-BCMA T cells infusion
timeFrame: 3 months post administration of CAR-T-cells
measure: Additional efficacy evaluation after 12 weeks of CT053 CAR-BCMA T cells infusion
timeFrame: 3 months post administration of CAR-T-cells
measure: Additional efficacy evaluation after 12 weeks of CT053 CAR-BCMA T cells infusion
timeFrame: 3 months post administration of CAR-T-cells
measure: Safety and tolerability of CAR-BCMA T cell therapy
timeFrame: through 24 months post administration of CAR-T-cells
measure: Pharmacokinetics (the cell persistence duration in peripheral blood)
timeFrame: through 24 months post administration of CAR-T-cells
measure: Pharmacokinetics (the cell persistence duration in peripheral blood)
timeFrame: through 24 months post administration of CAR-T-cells
measure: Safety and tolerability of CAR-BCMA T cell therapy
timeFrame: through 24 months post administration of CAR-T-cells
measure: Efficacy endpoint of CAR-BCMA T cells after infusion
timeFrame: through 24 months post administration of CAR-T-cells
measure: Efficacy endpoint of CAR-BCMA T cells after infusion
timeFrame: through 24 months post administration of CAR-T-cells
measure: Efficacy endpoint of CAR-BCMA T cells after infusion
timeFrame: through 24 months post administration of CAR-T-cells
measure: Efficacy endpoint of CAR-BCMA T cells after infusion
timeFrame: through 24 months post administration of CAR-T-cells
measure: Efficacy endpoint of CAR-BCMA T cells after infusion
timeFrame: through 24 months post administration of CAR-T-cells
measure: Efficacy endpoint of CAR-BCMA T cells after infusion
timeFrame: through 24 months post administration of CAR-T-cells
measure: Efficacy endpoint of CAR-BCMA T cells after infusion
timeFrame: through 24 months post administration of CAR-T-cells
measure: Efficacy endpoint of CAR-BCMA T cells after infusion
timeFrame: through 24 months post administration of CAR-T-cells
measure: Efficacy endpoint of CAR-BCMA T cells after infusion
timeFrame: through 24 months post administration of CAR-T-cells
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The first affiliated hospital of bengbu medical college
state: Anhui
city: Beijing
country: China
facility: Beijing Chaoyang hospital
state: Beijing
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Centre
state: Guangdong
city: Shenzhen
country: China
facility: The 2nd People's Hospital of Shenzhen
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Nantong
country: China
facility: Affiliated Hospital of Nantong University
state: Jiangsu
city: Suzhou
country: China
facility: The First Affiliated Hospital Of Soochow University
state: Jiangsu
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Hanzhou
country: China
facility: The first Affiliated Hospital, College of medicine, Zhejiang University
state: Zhejiang
city: Wenzhou
country: China
facility: The first Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
city: Beijing
country: China
facility: Beijing Boren Hospital
city: Beijing
country: China
facility: Beijing Hospital
city: Beijing
country: China
facility: Peking University People's Hospital
city: Beijing
country: China
facility: Peking University Third Hospital
city: Shanghai
country: China
facility: Tongji Hospital of Tongji University
city: Shanghai
country: China
facility: Xinhua Hospital Affiliated To Shanghai Jiaotong University School of Medicine
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
Study officials:
affiliation: Beijing Chao Yang Hospital
name: Wenming CHEN, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital of Soochow University
name: Zhengzheng FU, MD
role: PRINCIPAL_INVESTIGATOR
References: