Sequential Radiotherapy With CAR-T Cells in the Treatment of Relapsed and Refractory Hematological Malignancies With Extramedullary Lesions

Sponsor

Zhejiang University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04790747

Collaborator

Yake Biotechnology Ltd. (Industry)

Enrollment

Location

Arm

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Clinical trial for the safety and efficacy of sequential radiotherapy with CAR-T cells in the treatment of relapsed and refractory hematological malignancies with extramedullary lesions

Condition or Disease	Intervention/Treatment	Phase
Hematological Malignancies	Drug: CAR-T cells	Phase 1/Phase 2

Detailed Description

This is a prospective, single arm study. To evaluate the safety and efficacy of sequential radiotherapy with CAR-T cells in the treatment of relapsed and refractory hematological malignancies with extramedullary lesions. The main endpoints were dose limiting toxicity (DLT) and incidence of adverse events (TEAEs).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Clinical Trial for the Safety and Efficacy of Sequential Radiotherapy With CAR-T Cells in the Treatment of Relapsed and Refractory Hematological Malignancies With Extramedullary Lesions

Anticipated Study Start Date :

Mar 1, 2021

Anticipated Primary Completion Date :

Mar 1, 2024

Anticipated Study Completion Date :

Mar 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: radiotherapy and CAR-T therapy sequential radiotherapy and CAR-T cell therapy	Drug: CAR-T cells Each subject receives sequential radiotherapy and CAR-T cells by intravenous infusion

Arm

Intervention/Treatment

Experimental: radiotherapy and CAR-T therapy

sequential radiotherapy and CAR-T cell therapy

Drug: CAR-T cells

Each subject receives sequential radiotherapy and CAR-T cells by intravenous infusion

Outcome Measures

Primary Outcome Measures

Dose-limiting toxicity (DLT) [Baseline up to 28 days after CAR-T cells infusion]
Adverse events assessed according to NCI-CTCAE v5.0 criteria
Incidence of treatment-emergent adverse events (TEAEs) [Up to 2 years after CAR-T cells infusion]
Incidence of treatment-emergent adverse events [Safety and Tolerability]

Secondary Outcome Measures

Complete Remission Rate [up to 28 days after CAR-T cells infusion]
Complete Remission Rate after CAR-T cell therapy
Overall survival (OS) [Up to 2 years after CAR-T cells infusion]
From the first infusion of CD19 CAR-T cells to death or the last visit
Disease-free survival (DFS) [Up to 2 years after CAR-T cells infusion]
From the complete remission to the occurrence of any event, including death, relapse (any one occurs first), and the last visit
Quality of life [At Baseline, Month 1, 3, 6, 9 and 12]
Assessment using European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scale [For item1-28: max score: 112, min score: 28, higher scores mean a better outcome; for item 28-29: max score: 14, min score: 2, higher scores mean a worse outcome] to measure Quality of life at Baseline, Month 1, 3, 6, 9 and 12

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age≥15 years old; Relapsed and refractory hematological malignancies with extramedullary lesions, mainly including B-cell non Hodgkin's lymphoma, multiple myeloma, acute lymphoblastic leukemia, etc; Flow cytometry or pathological biopsy confirmed that tumor cells have potential therapeutic targets for Car-T cells; PET-CT confirmed that the extramedullary lesions were located in a single radiotherapy region; Anticipated survival time more than 12 weeks; Those who voluntarily participated in this trial and provided informed consent.

Exclusion Criteria:

History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases; Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past; Pregnant (or lactating) women; Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis); Active infection of hepatitis B virus or hepatitis C virus; Concurrent therapy with systemic steroids within 2 weeks prior to screening, except for the patients recently or currently receiving inhaled steroids; Previously treated with any CAR-T cell product or other genetically-modified T cell therapies; Creatinine>2.5mg/dl, or ALT / AST > 3 times of normal amounts, or bilirubin>2.0 mg/dl; Other uncontrolled diseases that were not suitable for this trial; Patients with HIV infection; Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.