A Multicenter Clinical Study on the Safety and Effectiveness of CAR-T in the Treatment of Relapsed/Refractory Hodgkin's Lymphoma

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

Study Overview

• Status: Recruiting
• Conditions: Hodgkin's Lymphoma
• Intervention / Treatment: Biological: Auto CAR-T; Drug: Cyclophosphamide,Fludarabine; Procedure: Leukapheresis

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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jianqiang Li, PhD & MD; Phone Number: 008615511369555; Email: limmune@gmail.com

Study Locations

• China
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • Recruiting
      • Hematology Department, Hebei Medical University Fourth Hospital
      • Contact: Lihong Liu, PhD & MD; Phone Number: +8613831177920; Email: limmune@gmail.com
      • Principal Investigator: Baoen Shan, PhD & MD
      • Principal Investigator: Lihong Liu, PhD & MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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. Hodgkin lymphoma patients who are judged to be relapsed/refractory by clinical diagnosis, relapse or refractory are defined as:

   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 after anti-PD-1 monoclonal antibody treatment 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;
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 CD30 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 functions need to meet the following conditions: serum creatinine ≤1.5 ULN, AST (aspartate aminotransferase)/ALT (alanine aminotransferase)/ALP (alkaline phosphatase) ≤2.5 ULN, total bilirubin ≤1.5 ULN, left Ventricular ejection fraction (LVEF) ≥50%, and minimum lung function reserve (dyspnea is not higher than level 1 and blood oxygen saturation is greater than 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.

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: Auto CAR-T; Patients will be treated with Auto CAR-T cells	Biological: Auto CAR-T; Biological: Auto CAR-T; Drug: Cyclophosphamide,Fludarabine; Drug: Cyclophosphamide,Fludarabine; Procedure: Leukapheresis; Leukapheresis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: Incidence and severity of adverse events	To evaluate the possible adverse events occurred within first one month after CAR-T infusion, including the incidence and severity of symptoms such as cytokine release syndrome and neurotoxicity	first one month after CAR-T infusion
Efficacy: Remission Rate	Remission Rate including complete remission (CR), partial remission (PR), objective response (ORR = CR + PR), disease stability (SD), disease progression (PD) and and unresponsive (NR)	3 months post CAR-T cells infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy:duration of response (DOR)	duration of response (DOR)	24 months after CAR-T infusion
Efficacy: progression-free survival (PFS)	progression-free survival (PFS) time	24 months after CAR-T infusion

Collaborators and Investigators

• Sponsor: Hebei Senlang Biotechnology Inc., Ltd.
• Collaborators: Hebei Medical University Fourth Hospital
• Investigators: Principal Investigator: Baoen Shan, PhD & MD, Hebei Medical University Fourth Hospital; Principal Investigator: Lihong Liu, PhD & MD, Hebei Medical University Fourth Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2020
• Primary Completion (Anticipated): October 21, 2023
• Study Completion (Anticipated): October 21, 2025

Study Registration Dates

• First Submitted: December 7, 2020
• First Submitted That Met QC Criteria: December 7, 2020
• First Posted (Actual): December 11, 2020

Study Record Updates

• Last Update Posted (Actual): December 29, 2020
• Last Update Submitted That Met QC Criteria: December 24, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease; 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: 2020103

Drug and device information, study documents

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