Allogeneic Stem Cell Transplantation in Relapsed/Refractory T-, NK/T-cell Lymphomas

Phase 2

Recruiting

• Conditions: T-cell Non-Hodgkin Lymphoma; Lymphoma, Extranodal NK-T-Cell
• Interventions: Drug: Busulfan; Drug: Fludarabine

• Registration Number: NCT02859402
• Lead Sponsor: Keimyung University Dongsan Medical Center

Brief Summary

Relapsed and refractory T-cell lymphomas have been reported to have dismal outcomes. The role of allogeneic stem cell transplantation have been demonstrated in these patients. This clinical trial is studying the efficacy and safety of busulfan plus fludarabine as conditioning therapy followed by allogeneic stem cell transplantation (Allo-SCT) in T- and NK/T-cell lymphoma patients who have relapsed or are refractory to previous chemotherapies including autologous transplantation.

Detailed Description

Conditioning therapy

* Busulfan (Busulfex®; Patheon Manufacturing Services LLC, Greenville, NC 27834) 3.2 mg/kg + 5% DW (the diluent quantity should be 10 times the volume of Busulfan, so that the final concentration of busulfan becomes approximately 0.5 mg/mL), intravenously for 3 hours once daily for 3 days (days -7 to -5)

* Fludarabine (Fludarabine®, Zydus Hospira Oncology Private Ltd., Ahmedabad, India) 30 mg/m2 + 5% DW 100㎖, intravenously for over 1 hour once daily for 6 days (days -8 to -3)

* Busulfan should be infused as soon as completion of fludarabine infusion

Primary objective of this study I. To determine the 2-year progression-free survival of this reduced toxicity conditioning in relapsed or refractory T- and NK/T-cell non-hodgkin lymphoma patients.

Secondary endpoints I. To evaluate the response rate, engraftment rate and time to engraftment, 2-year overall survival, 100-days treatment-related mortality, regimen-related toxicities by CTCAE version 4.03, post-transplantation complications (HVOD, acute/chronic graft-versus-host disease (GVHD), cytomegalovirus (CMV) infection,CMV disease) of this reduced toxicity conditioning in relapsed or refractory T- and NK/T-cell non-hodgkin lymphoma patients.

Study Timeline

• Study First Submitted: 2016-08-04
• Study First Submitted QC: 2016-08-08
• Study First Posted: 2016-08-09
• Study Start: 2016-12
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-17
• Last Update Posted: 2022-08-18
• Primary Completion: 2025-12
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 34

Inclusion Criteria

1. Age 19 - 65

2. Histologically confirmed T or NK cell lymphomas :

   • anaplastic large cell lymphoma
   • angioimmunoblastic T-cell lymphoma,
   • peripheral T-cell lymphoma, NOS
   • NK/T-cell lymphoma

3. Relapsed after or refractory to one or more of previous chemotherapy including frontline autologous HSCT.

4. At least one measured lesion using conventional CT or PET CT at the time of relapse after or refractory to one or more of previous chemotherapy and before salvage chemotherapy

5. Complete or Partial response after short cycles of salvage chemotherapy

6. Patients who have HLA full-match (8/8 in HLA-A, B, C, DR by DNA high-resolution technique) or one-locus mismatch (7/8) sibling, or unrelated bone marrow or peripheral blood or cord blood stem cell donors

7. ECOG performance status ≤ 2

8. Charlson Comorbidity Index (CCI) before HSCT ≤ 3

9. Adequate renal function : serum creatinine level < 2.0 mg/dL

10. Adequate liver function :

    • Transaminase (AST/ALT) < 3 X upper normal value (or < 5 x ULN in the presence of lymphoma involvement of the liver)
    • Total bilirubin < 2 X upper normal value (or < 5 x ULN in the presence of NK/T involvement of the liver)

11. Cardiac ejection fraction ≥ 50 % as measured by MUGA or 2D ECHO without clinically significant abnormality

12. No clinically significant infection

13. No clinically significant bleeding symptoms or sign

14. Patients who decided to participate in this study and signed for a written consent

Exclusion Criteria

1. Adult T cell leukemia/lymphoma, Lymphoblastic lymphoma, Primary cutaneous CD30+ T cell disorders Mycosis fungoides, Sezary SD

2. Patients who have previously performed Allo-HSCT

3. T cell lymphoma with primary central nervous system (CNS) Involvement.

   ** However, patients who have only had prophylactic intrathecal or intravenous chemotherapy against CNS disease are eligible.

4. Patients with a known history of HIV seropositivity or HCV (+).

   ** Patients with HBV are eligible. However, primary prophylaxis using antiviral agents is recommended for HBV carrier or prevent HBV reactivation during whole treatment period.

5. Any other malignancies within the past 5 years

   ** Except curatively treated non-melanoma skin cancer or in situ carcinoma of cervix uteri

6. Ejection fraction < 50% by a echocardiography

7. FEV1 <60% or DLCO <60% by a pulmonary function test

8. ECOG performance status 3 or 4

9. Combined serious medical problem or disease

   • Serious or unstable heart disease although proper treatment
   • Myocardial infarction in recent 3 months
   • Underlying serious neurologic or psychiatric disease including dementia or seizure
   • Active uncontrolled infection including hepatitis B and C
   • Serious other medical problems observed by the doctors in charge of the patient

10. Pregnant or lactating women, women of childbearing potential not employing adequate contraception

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental Arm	Busulfan	Conditioning chemotherapy: Fludarabine and Busulfan followed by Allogeneic stem cell transplantation
Experimental Arm	Fludarabine	Conditioning chemotherapy: Fludarabine and Busulfan followed by Allogeneic stem cell transplantation

Primary Outcome Measures

Name	Time	Method
2-year progression-free survival	2 years	2 year progression-free survival rate from the date of allogeneic stem cell transplantation. Estimated using the Kaplan-Meier method. Median value will be provided.

Secondary Outcome Measures

Name	Time	Method
Rate of hepatic venoocclusive disease (HVOD)	Day 30	Summarized using standard descriptive statistics.
Chronic GVHD grades I-IV	2 year	Summarized using standard descriptive statistics.
Acute graft-versus-host disease (GVHD) grades I-IV	Day 100	Summarized using standard descriptive statistics.
Response rate	3-months	Response will be measured after 3 months of the date of allogeneic stem cell transplantation. Mean value will be provided.
Time to neutrophil engraftment	Day 30	Summarized using standard descriptive statistics along with corresponding 95% confidence intervals.
Time to platelet engraftment	Day 30	Summarized using standard descriptive statistics along with corresponding 95% confidence intervals.
Rate of cytomegalovirus (CMV) infection	2 year	Summarized using standard descriptive statistics.
2-year overall survival	2 years	2 year overall survival rate from the date of allogeneic stem cell transplantation. Estimated using the Kaplan-Meier method. Median value will be provided.
100-days treatment-related mortality	Days 100	Summarized using standard descriptive statistics.
Rate of regimen-related toxicities	Day 30	Toxicity according to CTCAE version 4.03. Summarized using standard descriptive statistics.

Trial Locations

Locations (2)

Dong-A University; 🇰🇷 Busan, Korea, Republic of

Keimyung University Dongsan Medical Center; 🇰🇷 Daegu, Korea, Republic of