Autologous Hematopoietic Stem Cell Boost Study After CAR-T Therapy

Prospective Study of Autologous Hematopoietic Stem Cell Boost to Improve Myelosuppression in B-NHL Patients with High-risk Immunologic Hematologic Toxic After Chimeric Antigen Receptor T-Cell Immunotherapy

This is a prospective, single-arm, open study to observe the efficacy and safety of the CART-SCB regimen (Clinical Regimen for the Prospective Study of Autologous Hematopoietic Stem Cell Boost for the Improvement of Bone Marrow Suppression in Patients with High-Risk Immunohematologic Toxicity Lymphoma After Chimeric Antigen Receptor T (CAR-T)-Cell Immunotherapy Therapy) . After the patient has completed CAR-T therapy, if the patient has unrelieved hematologic toxicity, consider infusing a reserve of stem cells; if myelosuppression has not been significantly relieved, stem cell infusion can be performed again.

Study Overview

• Status: Recruiting
• Conditions: Diffuse Large B Cell Lymphoma
• Intervention / Treatment: Drug: autologous hematopoietic stem cell

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Weili Zhao, Doctor; Phone Number: 610707 +862164370045; Email: zhao.weili@yahoo.com
• Study Contact Backup: Name: Lingshuang Sheng, Doctor; Phone Number: 610707 +862164370045; Email: lssheng1122@163.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
    • Contact: Weili Zhao; Email: zwl_trial@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 years of age or older and gender-neutral;
• Diagnosis of B-cell non-Hodgkin lymphoma confirmed histologically or cytologically according to World Health Organization 2016 criteria;
• Prior CAR-T cell immunotherapy;
• Patients who are at high risk according to the CAR-HEMATOTOX score prior to leukapheresis; or patients who are clinically considered potentially at high risk for hematologic toxicity following immunotherapy (including age ≥60 years; or Eastern Cooperative Oncology Group (ECOG) Performance Status≥ 2 points; or number of prior lines of therapy ≥ 2, etc.);
• Myelosuppression as determined by the investigator has occurred after CAR-T therapy;
• Have a storage of stem cell;
• Stable lymphoma disease status (final investigator-assessed efficacy CR/PR);
• Bone marrow biopsy to rule out hemophilia/infection/bone marrow infiltration;
• Adequate organ function;
• Able to provide written informed consent (ICF) and able to understand and agree to comply with the study requirements and assessment schedule;
• Patients of childbearing potential must be willing to use highly effective contraception for the duration of the study, and for 120 days after the last dose of treatment.

Exclusion Criteria:

• History of allogeneic hematopoietic stem cell transplantation;
• History of epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving the central nervous system;
• Presence of or current concurrent other malignancies within the past 2 years, with the exception of cured carcinoma in situ of the uterine cervix, non-melanoma skin cancers, and superficial bladder tumors (Ta (non-invasive tumors), Tis (carcinoma in situ), and T1 (tumors infiltrating the basement membrane));
• Suffering from severe cardiovascular disease: grade II or greater myocardial ischemia or myocardial infarction, poorly controlled arrhythmias; grade III-IV cardiac insufficiency according to New York Heart Association (NYHA) criteria, or cardiac ultrasound suggestive of a left ventricular ejection fraction (LVEF) <50%;
• Allergy to any investigational drug or excipient;
• Presence of any active autoimmune disease (including, but not limited to: autoimmune hepatitis, interstitial pneumonitis, uveitis, enteritis, hepatitis, pituitary gland inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism), or known history of allograft transplantation, or patients with prolonged and heavy use of hormones or use of other immune-modulating agents or other patients who, as assessed by the Investigator Patients who are considered to have an impact on study treatment;
• Have an active infection;
• History of uncontrolled systemic disease, including diabetes mellitus, hypertension, and acute pulmonary disease;
• Known human immunodeficiency virus (HIV) infection;
• Presence of an underlying medical condition or alcohol/substance abuse or dependence that is not conducive to the administration of study medication, or that may interfere with the interpretation of results, or that puts the patient at high risk for developing treatment complications;
• End-organ damage due to autoimmune disease (e.g., Crohns disease, rheumatoid arthritis, systemic lupus erythematosus) within the past 2 years, or the need for systemic immunosuppression or other systemic disease-control medications.

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: Patients treated with stem cell boost; If the patient continues to have unrelieved hematologic toxicity after CAR-T cell therapy, consider infusing a reserve of stem cells; If there is no significant recovery from myelosuppression, another stem cell infusion can be performed.	Drug: autologous hematopoietic stem cell; Intervention were given myelosuppression occurring that cannot be controlled with other drugs as judged by the investigators

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year overall survival	Overall survival was defined as the time from the date of leukapheresis to the date of death from any cause.	1 year after CAR-T cell infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.	End of treatment visit (1 years after stem cell infusion)
Best objective response rate	Defined as the proportion of patients with an efficacy evaluation of complete response (CR) or partial response (PR) at any time point after infusing back CAR-T cells as a percentage of all patients, with efficacy assessed by the investigators according to the 2014 Lugano efficacy criteria	End of treatment visit (1 years after stem cell infusion)
Best complete response rate	Defined as the proportion of patients with an efficacy evaluation of CR at any time point after infusing back CAR-T cells as a percentage of all patients, with efficacy assessed by the investigators according to the 2014 Lugano efficacy criteria	End of treatment visit (1 years after stem cell infusion)
Time to reponse	Time from CAR-T cell infusion to the first assessment of CR or PR on the basis of investigator assessments according to 2014 Lugano criteria.	End of treatment visit (1 years after stem cell infusion)
Duration of response	Time from the first efficacy assessment of CR or PR to the time of first disease progression on the basis of investigator assessments according to 2014 Lugano criteria.	End of treatment visit (1 years after stem cell infusion)
Progression-free survival	Progression-free survival was defined as the time from the date of leukapheresis until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria, or death from any cause, whichever occurred first.	End of treatment visit (1 years after stem cell infusion)
Overall survival	Overall survival was defined as the time from the date of leukapheresis to the date of death from any cause.	End of treatment visit (1 years after stem cell infusion)
Overall days of hospitalization	Defined as total number of days admitted to the hospital since being infused back for CAR-T, including days of readmission for supportive care for myelosuppression	End of treatment visit (1 years after stem cell infusion)

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): October 15, 2024
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: September 2, 2024
• First Submitted That Met QC Criteria: September 5, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): October 23, 2024
• Last Update Submitted That Met QC Criteria: October 21, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Lymphoma, Large B-Cell, Diffuse
• Other Study ID Numbers: CART-SCB

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No