Clinical trial NCT06741813: Allo-HSCT vs ASCT in Adult T-LBL
Official title: Allogeneic Versus Autologous Hematopoietic Stem Cell Transplantation for Adult T Lymphoblastic Lymphoma as First-line Consolidation.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: T Lymphoblastic Lymphoma
Keywords: allogeneic hematopoietic stem cell transplantation
Autologous hematopoietic stem cell transplantation
T Lymphoblastic Lymphoma
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
First posted: 2024-12-19
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: For the adult patients (≥ 18 years) with Ann-Arbor stage III or IV T-LBL and achieving CR after 3 courses of induction chemotherapy, all the patients who fulfilled inclusion/exclusion criteria were randomly assigned in a 1:1 ratio to receive ASCT (ASCT group) or receive allo-HSCT (Allo-HSCT group). Patients would receive additional 1 course of chemotherapy after randomization and then received HSCT. Then we compared the clinical outcomes between the two groups.
Primary purpose: TREATMENT

Brief summary: 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?

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free survival
timeFrame: Probability of PFS at months 1, 2, 6, 12, 18 & 24 will be estimated from the Kaplan-Meier curves for each arm.
Secondary outcomes:
measure: Relapse
timeFrame: Cumulative incidence of disease progression/relapse at months 1, 2, 6, 12, 18 & 24 will be estimated, considering non-relapse mortality as competing events.
measure: Non-relapse mortality (NRM)
timeFrame: Cumulative incidence of NRM at months 1, 2, 6, 12, 18 & 24 will be estimated, considering disease progression/relapse as competing events.
measure: Overall survival (OS)
timeFrame: Probability of overall survival at months 1, 2, 6, 12, 18 & 24 will be estimated from the Kaplan-Meier curves for each arm.
Other outcomes:
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