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

NCT ID: NCT02859402

Last Updated: 2022-08-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-31
• Study Completion Date: 2027-12-31

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.

Conditions

T-cell Non-Hodgkin Lymphoma; Lymphoma, Extranodal NK-T-Cell

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental Arm

Conditioning chemotherapy: Fludarabine and Busulfan followed by Allogeneic stem cell transplantation

Group Type: EXPERIMENTAL

Busulfan

Intervention Type: DRUG

intravenous, 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), once daily for 3 hours for 3 days (days -7 to -5)

Fludarabine

Intervention Type: DRUG

intravenous, 30 mg/m2 + 5% DW 100㎖, over 1 hour once daily for 6 days (days -8 to -3)

Interventions

Busulfan

intravenous, 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), once daily for 3 hours for 3 days (days -7 to -5)

Intervention Type: DRUG

Fludarabine

intravenous, 30 mg/m2 + 5% DW 100㎖, over 1 hour once daily for 6 days (days -8 to -3)

Intervention Type: DRUG

Other Intervention Names

Busulfex

Eligibility Criteria

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

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Otsuka Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Keimyung University Dongsan Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Young Rok Do

Prof.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Dong-A University

Busan, , South Korea

Site Status: RECRUITING

Keimyung University Dongsan Medical Center

Daegu, , South Korea

Site Status: RECRUITING

Countries

South Korea

Central Contacts

Young Rok Do, MD., Ph.D.

Role: CONTACT

dyr1160@dsmc.or.kr

+82-10-3541-1160

Ji Hyun Lee, MD., Ph.D.

Role: CONTACT

hidrleejh@dau.ac.kr

+82-10-9397-5694

Facility Contacts

Ji Hyun Lee, MD., Ph.D.

Role: primary

hidrleejh@dau.ac.kr

+82-10-9397-5694

Young Rok Do, MD., Ph.D.

Role: primary

dyr1160@dsmc.or.kr

+82-10-3541-1160

Other Identifiers

DSMC 2016-05-051

Identifier Type: -

Identifier Source: org_study_id