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

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

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

Study Overview

• Status: Recruiting
• Conditions: Hematological Malignancies
• Intervention / Treatment: Drug: CAR-T cells

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 Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The First Hospital of Zhejiang Medical Colleage Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life	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	At Baseline, Month 1, 3, 6, 9 and 12
Complete Remission Rate	Complete Remission Rate after CAR-T cell therapy	up to 28 days after CAR-T cells infusion
Overall survival (OS)	From the first infusion of CD19 CAR-T cells to death or the last visit	Up to 2 years after CAR-T cells infusion
Disease-free survival (DFS)	From the complete remission to the occurrence of any event, including death, relapse (any one occurs first), and the last visit	Up to 2 years after CAR-T cells infusion

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: Yake Biotechnology Ltd.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): March 1, 2021
• Primary Completion (ANTICIPATED): March 1, 2024
• Study Completion (ANTICIPATED): March 1, 2025

Study Registration Dates

• First Submitted: March 8, 2021
• First Submitted That Met QC Criteria: March 8, 2021
• First Posted (ACTUAL): March 10, 2021

Study Record Updates

• Last Update Posted (ACTUAL): March 10, 2021
• Last Update Submitted That Met QC Criteria: March 8, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: CAR-T; radiotherapy; relapsed and refractory; extramedullary lesions
• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms
• Other Study ID Numbers: EML-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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