Clinical trial NCT04665076: Multicenter Clinical Study on the Safety and Effectiveness of CAR-T in the Treatment of Relapsed/Refractory Plasma Cell Tumors
Official title: Multicenter Clinical Study on the Safety and Effectiveness of CAR-T in the Treatment of Relapsed/Refractory Plasma Cell Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Plasma Cell Tumors
Lead sponsor: Hebei Senlang Biotechnology Inc., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Hebei Medical University Fourth Hospital
First posted: 2020-12-11
Enrollment: 60
Sex: ALL
Minimum age (years): 14
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is a multi-center, non-randomized, single-arm, open clinical trial.

Detailed description: A single car consists of scFv, hinge region, transmembrane region, costimulatory domain and zeta subunit of CD3.Prior to CAR-T cell infusion, the patients will be subjected to preconditioning treatment. After CAR-T cell infusion, the patients will be evaluated for adverse reactions and efficacy.

Eligibility criteria: Inclusion Criteria:

1. Fully understand and voluntarily sign the informed consent form, and be willing and able to comply with the visits, treatment plans, laboratory inspections, and other requirements of the research as specified in the test procedure;
2. Patients with relapsed/refractory plasma cell tumors determined by clinical diagnosis;

   The definition of relapsed/refractory plasma cell tumors is:
   1. Primary resistance to standard treatment regimens;
   2. Or PD occurs after standard treatment with at least second-line standard treatment plan;
   3. Or the last treatment effect is SD and the duration does not exceed 6 months;
   4. Or treatment with proteasome inhibitors and immunomodulators is ineffective or relapses;
   5. Patients who have PD after autologous hematopoietic stem cell transplantation or confirmed recurrence by biopsy within 12 months, or patients who undergo salvage treatment after autologous hematopoietic stem cell transplantation have no remission or relapse after treatment.
3. According to RECIST version 1.1 , there should be at least one measurable tumor (soft tissue mass) or serum M protein ≥10g/L or urine M protein ≥200mg/24h;
4. Subjects whose physical status scored by the Eastern Cooperative Oncology Group (ECOG) is 0\~2;
5. 14 years old ≤ age ≤ 75 years old, both male and female;
6. Immunohistochemistry or flow cytometry detects tumor cells as BCMA or CD19/CD22/CD79 positive;
7. The estimated survival period from the date of signing the informed consent form is greater than 3 months;
8. Laboratory examinations meet the following conditions: hemoglobin ≥80g/L, platelet count ≥50 × 109/L, absolute neutrophil count (ANC) ≥1.0 × 109/L, if the investigator believes that the above inspection value is below the lower limit It is caused by tumor invading bone marrow and can be included in the group after consultation with the sponsor;
9. The main organ function indicators meet the following conditions: AST (aspartate aminotransferase)/ALT (alanine aminotransferase)/ALP (alkaline phosphatase) ≤2.5 ULN, serum creatinine ≤1.5 ULN, total bilirubin ≤1.5 ULN, left Ventricular ejection fraction (LVEF) ≥50%, and minimum pulmonary function reserve (dyspnea is not higher than grade 1 and blood oxygen saturation\> 92% under indoor conditions).

Exclusion Criteria:

1. Severe cardiac insufficiency, left ventricular ejection fraction \<50%;
2. There is a history of severe lung dysfunction diseases;
3. The patient has had other malignant tumors in the past 5 years, except for skin basal cell carcinoma, breast carcinoma in situ and cervical carcinoma in situ that have undergone radical treatment;
4. Combined with severe or persistent infection and cannot be effectively controlled; Severe infection: Refers to sepsis or uncontrolled infection of the infected foci, and can be included in the group after infection is controlled
5. Combined metabolic diseases (except diabetes);
6. Combined with severe autoimmune disease or innate immune deficiency;
7. Untreated active hepatitis (hepatitis B, defined as hepatitis B virus surface antigen \[HBsAg\] test results are positive, HBV-DNA ≥ 500 IU/ml and abnormal liver function; hepatitis C, defined as hepatitis C antibody \[ HCV-Ab\] positive, HCV-RNA higher than the detection limit of the analysis method and abnormal liver function) or combined with hepatitis B and C co-infection;
8. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), or syphilis infection;
9. A history of severe allergies to biological products (including antibiotics);
10. Participate in any other clinical drug trials at the same time within one month;
11. There are other serious physical or mental illnesses or laboratory abnormalities that may increase the risk of participating in the research, or interfere with the results of the research, and patients who the researcher believes are not suitable for participating in this research.

Primary outcomes:
measure: Safety: Incidence and severity of adverse events
timeFrame: first one month after CAR-T infusion
measure: Efficacy: Remission Rate
timeFrame: 3 months post CAR-T cells infusion
Secondary outcomes:
measure: Efficacy:duration of response (DOR)
timeFrame: 24 months after CAR-T infusion
measure: Efficacy: progression-free survival (PFS)
timeFrame: 24 months after CAR-T infusion
Other outcomes:
Locations:
city: Shijiazhuang
country: China
facility: Hematology Department, Hebei Medical University Fourth Hospital
state: Hebei
Study officials:
affiliation: Hebei Medical University Fourth Hospital
name: Baoen Shan, PhD & MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hebei Medical University Fourth Hospital
name: Lihong Liu, PhD & MD
role: PRINCIPAL_INVESTIGATOR
References: