Reduced Intensity Conditioning With Thiotepa Combined With Bu/Flu/Ara-C in Allo-HSCT for Relapsed or Refractory Peripheral T-cell Lymphoma.

Peripheral T Cell Lymphoma Clinical Trial

Official title:

Reduced Intensity Conditioning With Thiotepa Combined With Busulfan, Fludarabine and Cytarabine in Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of Relapsed or Refractory Peripheral T-cell Lymphoma.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06468267
• Other study ID #: SHSYXY-202402-THI-FAB
• Status: Recruiting
• Phase: Phase 2
• Start date: June 2024
• Est. completion date: June 2026

Study information

• Verified date: June 2024
• Source: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
• Contact: xianmin Song, MD
• Phone: +86 1350167250
• Email: shongxm[@]139.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a multicenter, single-arm, prospective phase II clinical trial that evaluates the efficacy and safety of an intensive conditioning regimen with thiotepa combined with busulfan, fludarabine, and cytarabine for allogeneic hematopoietic stem cell transplantation in the treatment of myeloid malignancies with extramedullary involvement. The conditioning regimen includes thiotepa at a dose of 5mg/kg/d at d -7 (1 day), fludarabine at 30mg/m2/d from d -6 to d -2 (5 days), cytarabine at 1g/m2/d from d -6 to d -2 (5 days), and busulfan at 3.2mg/kg/d from d -4 to d -3 (2 days). Conditioning begins on day -7, and donor hematopoietic stem cell infusion is performed on day 0. All patients will undergo bone marrow examination on day 14 and day 28 post-transplant, followed by bone marrow examinations every 30 days within the first year after transplantation, and every 60 days within the second year after transplantation. If disease relapse is suspected during the follow-up period, bone marrow or extramedullary relapse site examinations will be conducted at any time. The primary study endpoints are the 1-year and 2-year progression-free survival (PFS) rates post-transplant. Secondary study endpoints include the incidence of acute graft-versus-host disease (GVHD) within 180 days post-transplant, cumulative relapse rates at 1 year and 2 years post-transplant, 1-year and 2-year overall survival (OS), graft-versus-host disease-free, relapse-free survival (GRFS), non-relapse mortality (NRM), cumulative incidence of chronic GVHD, and the incidence of Cytomegalovirus （CMV）and Epstein-Barr virus（EBV）reactivation within 1 year.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: June 2026
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Age between 18 and less than 70 years, regardless of gender

2. Peripheral T-cell lymphoma (PTCL) was diagnosed according to the 2016 WHO criteria and met any of the following criteria:

1) High risk: IPI score = 3 or aaIPI score = 2 ( aaIPI is suitable for patients younger than 60 years old).

2) Patients who achieved CR or PR after first-line chemotherapy (PET-CT or CT examination was performed according to the patient 's economic conditions)

3.Patients must have a suitable hematopoietic stem cell donor:

1. Related donors must have at least 5/10 matches for HLA-A, -B, -C, -DQB1, and - DRB1.

2. Unrelated donors must have at least 8/10 matches for HLA-A, -B, -C, -DQB1, and -DRB1.

4.Hematopoietic cell transplantation comorbidity index (HCT-CI) score = 2.

5.ECOG (Eastern Cooperative Oncology Group) performance status: 0-2.

6.Adequate liver, kidney, and cardiopulmonary function, meeting the following requirements:

a.Serum creatinine = 1.5x ULN (the upper limit of normal). b.Cardiac function: Ejection fraction = 50%. c.Baseline oxygen saturation > 92%. d.Total bilirubin = 2.0 x ULN; ALT and AST = 2.0 x ULN,AKP = 2.0 x ULN e.Pulmonary function: DLCO (corrected for hemoglobin) = 40% and FEV1 (Forced Expiratory Volume in 1 second) = 50%.

7.Patients must have the ability to understand and be willing to participate in this study and sign an informed consent form.

Exclusion Criteria:

1. PTCL patients did not meet the criteria of high-risk.

2. PTCL ALK + patients with CR after first-line treatment.

3. History of malignancies other than lymphoid tumors within the 5 years prior to screening, except for adequately treated in situ cervical cancer, basal cell carcinoma, squamous cell carcinoma of the skin, and curatively treated localized prostate cancer or ductal carcinoma in situ

4. ECOG = 3.

5. HCT-CI score = 3.

6. Any unstable systemic diseases, including but not limited to unstable angina, recent cerebrovascular accidents or transient ischemic attacks within the 3 months prior to screening, myocardial infarction within the 3 months prior to screening, congestive heart failure (New York Heart Association [NYHA] class = III), severe arrhythmias requiring drug treatment after pacemaker implantation, significant liver, kidney, or metabolic diseases, and pulmonary arterial hypertension.

7. Active, uncontrolled infections, including those associated with hemodynamic instability, new or worsening infection symptoms or signs, new infectious lesions on imaging, or persistent unexplained fever without signs or symptoms of infection.

8. HIV-infected individuals.

9. Active hepatitis B (HBV) or active hepatitis C (HCV) requiring antiviral therapy.

Patients at risk of HBV reactivation, are defined as those who are positive for hepatitis B surface antigen or core antibody without receiving antiviral therapy.

10. History of autoimmune diseases

11. Pregnant or breastfeeding women.

12. Fertile males and females unwilling to use contraception during the treatment period and for 12 months after treatment.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• Peripheral T Cell Lymphoma

Intervention

Drug:
• Thiotepa
The reduced intensity conditioning regimen is composed by thiotepa (5mg / kg / d-7d (1d)), fludarabine (30mg / m2 / d, -6d--2d (5d)), Ara-C (1g / m2 / d, -6d--2d (5d)), and busulfan (3.2mg / m2 / d, -4d-3d (2d)).

Locations

Country	Name	City	State
China	Shanghai General Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Xianmin Song, MD

Country where clinical trial is conducted

China, 

References & Publications (15)

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* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1y and 2y-PFS	1-year and 2-year progression-free survival (PFS) rates post-transplant	up to 1 years for the 1y-PFS and up to 2 years for the 2y-PFS
Secondary	aGVHD	acute graft-versus-host disease (GVHD) within 180 days post-transplant	up to 180 days
Secondary	1y and 2y-CIR	cumulative relapse rates (CIR) at 1 year and 2 years post-transplant	up to 1 years for the 1y-CIR and up to 2 years for the 2y-CIR
Secondary	1y and 2y-OS	overall survival (OS) at 1 year and 2 years post-transplant	up to 1 years for the 1y-OS and up to 2 years for the 2y-OS
Secondary	GRFS	graft-versus-host disease-free, relapse-free survival (GRFS) at 2 years post-transplant	up to 2 years
Secondary	NRM	non-relapse mortality (NRM) at 2 years post-transplant	up to 2 years
Secondary	cGVHD	cumulative incidence of chronic GVHD at 2 years post-transplant	up to 2 years
Secondary	CMV and EBV reactivation	the incidence of CMV and EBV reactivation within 1 year	up to 1 year