Relmacabtagene Autoleucel Combined With Autologous Hematopoietic Stem Cell Transplantation, Orelabrutinib, and Sintilimab for Primary Central Nervous System Lymphoma

Official title

A Prospective, Multicenter Clinical Study of Relmacabtagene Autoleucel Combined With Autologous Hematopoietic Stem Cell Transplantation, Orelabrutinib, and Sintilimab for Primary Central Nervous System Lymphoma

Overview

To evaluate the efficacy and safety of relmacabtagene autoleucel combined with autologous hematopoietic stem cell transplantation, orelabrutinib, and sintilimab as first-line or relapsed/refractory treatment for primary central nervous system diffuse large B-cell lymphoma.

Interventions

• Drug Relmacabtagene autoleucel and transplantation
  This study enrolled patients with primary central nervous system lymphoma, from whom mononuclear cells and hematopoietic stem cells were collected. Participants receive infusions of hematopoietic stem cells and CAR-T cells, followed by maintenance therapy with orelabrutinib and sintilimab starting on day 15 post-transplantation, for a median duration of up to 6 months and 1 year, respectively.

Primary outcome measures

• progression-free survival(PFS) [Time frame: Up to 60 months]
• overall response rate(ORR) [Time frame: Up to 3 months]

Secondary outcome measures (1)

• Overall Survival (OS) [Time frame: Up to 60 months]

Eligibility criteria

Inclusion criteria

1.18-60 years 2.ECOG performance status 0-2 3.No prior treatment with CAR-T cell therapy or autologous stem cell transplantation (ASCT) 4.Expected survival ≥ 3 months 5.No history of malignancy (except for in situ carcinoma or other indolent malignancies), or inactive malignancy with treatment completed >1 year ago 6.Histopathologically confirmed PCNSL (lymphoma confined to the brain without systemic involvement, with histopathological type being diffuse large B-cell lymphoma, or systemic lymphoma with central nervous system involvement and histopathological type being diffuse large B-cell lymphoma) 7.Refractory disease is defined as failure to achieve complete remission after first-line therapy (excluding intolerance to first-line therapy), including: Progressive disease (PD) as best response to first-line therapy, or Stable disease (SD) as best response after at least 4 cycles of first-line therapy (e.g., 4 cycles of R-CHOP), or Residual disease after at least 6 cycles of first-line therapy, or relapse within 12 months after completing first-line therapy 8.Relapsed disease is defined as recurrence after achieving complete remission following first-line therapy, occurring within 12 months after treatment completion 9.Positive CD19 expression by immunohistochemistry 10.No contraindications for CAR-T cell therapy or ASCT 11.No concurrent use of other anti-tumor therapies during this treatment; bisphosphonates for bone metastases and symptomatic supportive treatments are allowed 12.Able to understand the study and provide signed Informed Consent Form

Exclusion criteria

• Pregnant or lactating women
• Any uncontrolled medical condition (including active infection, uncontrolled diabetes, severe cardiac, hepatic or renal insufficiency, interstitial pneumonia, etc.)
• Use of systemic corticosteroids within 7 days before CD19 CAR-T cell infusion (except ≤ 5 mg/day dexamethasone or equivalent doses of other corticosteroids)
• Prior exposure to ≥ 2 of the following agents with documented resistance: orelabrutinib, fotemustine, carmustine, thiotepa, or PD-1/PD-L1 inhibitors
• History of autoimmune disease
• Presence of cachexia or any other contraindication to chemotherapy
• Active, uncontrolled infection
• History of poorly controlled psychiatric disorder
• Any condition that, in the opinion of the investigator, would preclude safe participation in this trial

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07198464 · IIT-ZD-003-ATT02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗