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

Sponsor

Keimyung University Dongsan Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT02859402

Collaborator

Otsuka Pharmaceutical Co., Ltd. (Industry)

Enrollment

Locations

Arm

132

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
T-cell Non-Hodgkin Lymphoma Lymphoma, Extranodal NK-T-Cell	Drug: Busulfan Drug: Fludarabine	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

34 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Allogeneic Stem Cell Transplantation With 3-days Busulfan Plus Fludarabine as Conditioning in Patients With Relapsed or Refractory T-, NK/T-cell Lymphomas

Actual Study Start Date :

Dec 1, 2016

Anticipated Primary Completion Date :

Dec 1, 2025

Anticipated Study Completion Date :

Dec 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental Arm Conditioning chemotherapy: Fludarabine and Busulfan followed by Allogeneic stem cell transplantation	Drug: 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) Other Names: Busulfex Drug: Fludarabine intravenous, 30 mg/m2 + 5% DW 100㎖, over 1 hour once daily for 6 days (days -8 to -3)

Arm

Intervention/Treatment

Experimental: Experimental Arm

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

Drug: 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)

Other Names:

Busulfex

Drug: Fludarabine

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

Outcome Measures

Primary Outcome Measures

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

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.
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.
Rate of hepatic venoocclusive disease (HVOD) [Day 30]
Summarized using standard descriptive statistics.
Acute graft-versus-host disease (GVHD) grades I-IV [Day 100]
Summarized using standard descriptive statistics.
Chronic GVHD grades I-IV [2 year]
Summarized using standard descriptive statistics.
Rate of cytomegalovirus (CMV) infection [2 year]
Summarized using standard descriptive statistics.

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Age 19 - 65
Histologically confirmed T or NK cell lymphomas :

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

Relapsed after or refractory to one or more of previous chemotherapy including frontline autologous HSCT.
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
Complete or Partial response after short cycles of salvage chemotherapy
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
ECOG performance status ≤ 2
Charlson Comorbidity Index (CCI) before HSCT ≤ 3
Adequate renal function : serum creatinine level < 2.0 mg/dL
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)

Cardiac ejection fraction ≥ 50 % as measured by MUGA or 2D ECHO without clinically significant abnormality
No clinically significant infection
No clinically significant bleeding symptoms or sign
Patients who decided to participate in this study and signed for a written consent

Exclusion Criteria:

Adult T cell leukemia/lymphoma, Lymphoblastic lymphoma, Primary cutaneous CD30+ T cell disorders Mycosis fungoides, Sezary SD
Patients who have previously performed Allo-HSCT
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.

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.

Any other malignancies within the past 5 years

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

Ejection fraction < 50% by a echocardiography
FEV1 <60% or DLCO <60% by a pulmonary function test
ECOG performance status 3 or 4
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