Allo-HSCT vs ASCT in Adult T-LBL (TROPHY-NHL01)

Allogeneic Versus Autologous Hematopoietic Stem Cell Transplantation for Adult T Lymphoblastic Lymphoma as First-line Consolidation.

Autologous hematopoietic stem cell transplantation (ASCT) is the important consolidation for adult T-LBL. Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is also the important consolidation for adult T-LBL. So ASCT vs allo-HSCT: which is better consolidation for adult T-LBL?

Study Overview

• Status: Not yet recruiting
• Conditions: T Lymphoblastic Lymphoma
• Intervention / Treatment: Procedure: ASCT; Procedure: Allo-HSCT

Detailed Description

1. Characteristics of adult T-lymphoblastic lymphoma (T-LBL) T-lymphoblastic lymphoma (T-LBL) is a highly aggressive lymphoma which shares biological and morphological features with T-cell acute lymphoblastic leukemia (T-ALL), and T-LBL is conventionally distinguished from T-ALL by less than 25% bone marrow (BM) infiltrating blasts cells. T-LBL only represents 3-4% of adult's non-Hodgkin lymphomas (NHL) which is a rare histologic subtype of NHL in adults. For this reason, few studies had focused on the disease-specific cohort of adult T-LBL patients and most of the studies included both T-LBL and T-ALL.

2. Autologous hematopoietic stem cell transplantation (ASCT) is the important consolidation for adult T-LBL The treatment paradigm of T-LBL is evolving. In the 1980s, when patients were treated with lymphoma-like regimens, the outcome of T-LBL was dismal and the 5-year progression-free survival (PFS) and overall survival (OS) was only 22% and 32%, respectively. ALL-like regimens significantly increase the complete response (CR) rate to more than 90% in T-LBL patients; however, disease relapse negatively impacts the long-term survival. For example, the 3-year OS rates of T-LBL could be as high as 66.9% to 70% while the 5-year OS rates decrease to below 50% in adults.

   ASCT is an important consolidation for adult T-LBL, which could also improve the survival of T-LBL compared with those only receiving chemotherapy. However, for patients with some risk factors (such as central nervous system [CNS] involvement or bone marrow [BM] involvement), the survival was very poor. In addition, ASCT is associated with a significantly higher risk of disease progression or recurrence.

3. Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is also the important consolidation for adult T-LBL Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most important curative treatments for T-LBL mainly because of the graft-versus-lymphoma effect, particularly for those with high-risk characteristics of relapse. Recently, in a multicenter study of China enrolled 130 Ann-Arbor stage III or IV T-LBL patients (> 16 years) treated with allo-HSCT, the 2-year probabilities of disease progression, PFS, OS and NRM after allo-HSCT were 21.0%, 69.8%, 79.5%, and 9.2%, respectively. Patients with CNS involvement had a higher cumulative incidence of disease progression compared with those without CNS involvement (57.1% vs. 18.9%, P = 0.014). Patients receiving allo-HSCT in non-remission (NR) had a poorer PFS compared with those receiving allo-HSCT in complete remission (CR) or partial remission (PR) (49.2% vs. 72.7%, P = 0.041). Particularly, for patients with BM involvement and achieving CR before allo-HSCT, measurable residual disease (MRD) positivity before allo-HSCT was associated with a poorer PFS compared with MRD negativity (62.7% vs. 86.8 %, HR 1.94, P = 0.036). Thus, this real-world data suggested that allo-HSCT appeared to be an effective therapy for adults T-LBL patients with Ann-Arbor stage III or IV disease.
4. ASCT vs allo-HSCT: which is better consolidation for adult T-LBL Thus far, whether allo-HSCT could be superior to ASCT as consolidation in T-LBL was unknown, which should be identified by randomized controlled trials.

• Study Type: Interventional
• Enrollment (Estimated): 230
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiao-Dong Mo None; Phone Number: 13810096698; Email: moxiaodong@pkuph.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1) Newly diagnosed T-LBL; 2) 18-65 years of age at the time of diagnosis; 3) Categorized into Ann-Arbor stage III or IV; 4) Achieving complete response (CR) after 3 courses of induction chemotherapies; 5) ECOG PS score 0 or 1; 6) It needs consent from the patients or/and legal guardian, and signature on the Informed Consent.

Exclusion Criteria:

• 1) Newly diagnosed T-LBL, but categorized into Ann-Arbor stage I or II; 2) < 18 years, or older than 65 years at the time of diagnosis; 3) Achieving CR after 4 or more courses of induction chemotherapies, or could not achieve at least CR after induction chemotherapies; 4) with > 25% BM involvement or > 5% lymphoma cells in the peripheral blood; 5) ECOG PS score of 2 or more; 6) Patients with other comorbidities or mental diseases that influence the life safety and compliance of patients as well as affect informed consent, enrollment in the research, follow-up visit or result interpretation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ASCT group; T-LBL patients achieving CR after induction chemotherapy and then received ASCT as first line consolidation	Procedure: ASCT; The chemotherapy-based preconditioning regimen was BeEAM, which consisted of bendamustine (120-180 mg·m-2·day-1，days -8 to -7), etoposide (200 mg·m-2·day-1，days -6 to -3), cytarabine (400 mg·m-2·day-1，days -6 to -3), and melphalan (140 mg·m-2·day-1，days -2).
Experimental: Allo-HSCT; T-LBL patients achieving CR after induction chemotherapy and received allo-HSCT as first line consolidation	Procedure: Allo-HSCT; Chemotherapy-based preconditioning regimen consisted of cytarabine 4 g·m-2·day-1 (days -9), busulfan (3.2 mg·kg-1·day-1 administered intravenously on days -8 to -6) (day 0 being the first day of donor cell infusion), cyclophosphamide (1.8 g·m-2·day-1, days -5 to -4), and semustine (250 mg.m-2, day -3). For the patients older than 55 years old or with HCT-CI score of 3 or more, cyclophosphamide can be decreased to 1.0 g·m-2·day-1, days -5 to -4, and added fludarabine (30mg·m-2·day-1, days -6 to -2). Rabbit antithymocyte globulin (thymoglobulin, 1.5 to 2.5 mg/kg, days -5 to -2; Sanofi, France) was administered to the HID and URD groups or MSD HSCT recipients who older than 40 years old (1.5 mg/kg, days -4 to -2). All MSD, HID, and URD HSCT recipinets received cyclosporine A (CsA), mycophenolate mofetil (MMF), and short-term methotrexate (MTX) for GVHD prophylaxis. CsA (2.5 mg/kg, q12h, intravenous [i.v.]) was used from day -9, of which the trough concentration was adjusted to 150-250 ng

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Progression-free survival (PFS), defined as the time from the date of randomization to the date of disease progression/relapse, or death due to any cause.	Probability of PFS at months 1, 2, 6, 12, 18 & 24 will be estimated from the Kaplan-Meier curves for each arm.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse	Relapse, defined as the time from date of randomization to date of disease progression/relapse.	Cumulative incidence of disease progression/relapse at months 1, 2, 6, 12, 18 & 24 will be estimated, considering non-relapse mortality as competing events.
Non-relapse mortality (NRM)	NRM, defined as the time from date of randomization to date of death not preceded by disease progression/relapse.	Cumulative incidence of NRM at months 1, 2, 6, 12, 18 & 24 will be estimated, considering disease progression/relapse as competing events.
Overall survival (OS)	OS, defined as the time from the date of randomization to the date of death due to any cause.	Probability of overall survival at months 1, 2, 6, 12, 18 & 24 will be estimated from the Kaplan-Meier curves for each arm.

Collaborators and Investigators

• Sponsor: Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: December 15, 2024
• First Submitted That Met QC Criteria: December 15, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 15, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: allogeneic hematopoietic stem cell transplantation; Autologous hematopoietic stem cell transplantation; T Lymphoblastic Lymphoma
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: Peking University People's Hos

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