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

Primary Purpose

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

Status
Recruiting
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Busulfan
Fludarabine
Sponsored by
Keimyung University Dongsan Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for T-cell Non-Hodgkin Lymphoma focused on measuring T-cell Non-Hodgkin Lymphoma, NK/T-cell Non-Hodgkin Lymphoma, Relapsed, refractory, Conditioning, Allogeneic stem cell transplantation

Eligibility Criteria

19 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Dong-A UniversityRecruiting
  • Keimyung University Dongsan Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Experimental Arm

Arm Description

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

Outcomes

Primary Outcome Measures

2-year progression-free survival
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
Response will be measured after 3 months of the date of allogeneic stem cell transplantation. Mean value will be provided.
Time to neutrophil engraftment
Summarized using standard descriptive statistics along with corresponding 95% confidence intervals.
Time to platelet engraftment
Summarized using standard descriptive statistics along with corresponding 95% confidence intervals.
2-year overall survival
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
Summarized using standard descriptive statistics.
Rate of regimen-related toxicities
Toxicity according to CTCAE version 4.03. Summarized using standard descriptive statistics.
Rate of hepatic venoocclusive disease (HVOD)
Summarized using standard descriptive statistics.
Acute graft-versus-host disease (GVHD) grades I-IV
Summarized using standard descriptive statistics.
Chronic GVHD grades I-IV
Summarized using standard descriptive statistics.
Rate of cytomegalovirus (CMV) infection
Summarized using standard descriptive statistics.

Full Information

First Posted
August 4, 2016
Last Updated
August 17, 2022
Sponsor
Keimyung University Dongsan Medical Center
Collaborators
Otsuka Pharmaceutical Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT02859402
Brief Title
Allogeneic Stem Cell Transplantation in Relapsed/Refractory T-, NK/T-cell Lymphomas
Acronym
RRTCLAlloSCT
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 2016 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Keimyung University Dongsan Medical Center
Collaborators
Otsuka Pharmaceutical Co., Ltd.

4. Oversight

Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
T-cell Non-Hodgkin Lymphoma, Lymphoma, Extranodal NK-T-Cell
Keywords
T-cell Non-Hodgkin Lymphoma, NK/T-cell Non-Hodgkin Lymphoma, Relapsed, refractory, Conditioning, Allogeneic stem cell transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
34 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental Arm
Arm Type
Experimental
Arm Description
Conditioning chemotherapy: Fludarabine and Busulfan followed by Allogeneic stem cell transplantation
Intervention Type
Drug
Intervention Name(s)
Busulfan
Other Intervention Name(s)
Busulfex
Intervention Description
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
Intervention Name(s)
Fludarabine
Intervention Description
intravenous, 30 mg/m2 + 5% DW 100㎖, over 1 hour once daily for 6 days (days -8 to -3)
Primary Outcome Measure Information:
Title
2-year progression-free survival
Description
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.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Response rate
Description
Response will be measured after 3 months of the date of allogeneic stem cell transplantation. Mean value will be provided.
Time Frame
3-months
Title
Time to neutrophil engraftment
Description
Summarized using standard descriptive statistics along with corresponding 95% confidence intervals.
Time Frame
Day 30
Title
Time to platelet engraftment
Description
Summarized using standard descriptive statistics along with corresponding 95% confidence intervals.
Time Frame
Day 30
Title
2-year overall survival
Description
2 year overall survival rate from the date of allogeneic stem cell transplantation. Estimated using the Kaplan-Meier method. Median value will be provided.
Time Frame
2 years
Title
100-days treatment-related mortality
Description
Summarized using standard descriptive statistics.
Time Frame
Days 100
Title
Rate of regimen-related toxicities
Description
Toxicity according to CTCAE version 4.03. Summarized using standard descriptive statistics.
Time Frame
Day 30
Title
Rate of hepatic venoocclusive disease (HVOD)
Description
Summarized using standard descriptive statistics.
Time Frame
Day 30
Title
Acute graft-versus-host disease (GVHD) grades I-IV
Description
Summarized using standard descriptive statistics.
Time Frame
Day 100
Title
Chronic GVHD grades I-IV
Description
Summarized using standard descriptive statistics.
Time Frame
2 year
Title
Rate of cytomegalovirus (CMV) infection
Description
Summarized using standard descriptive statistics.
Time Frame
2 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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 Pregnant or lactating women, women of childbearing potential not employing adequate contraception
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Young Rok Do, MD., Ph.D.
Phone
+82-10-3541-1160
Email
dyr1160@dsmc.or.kr
First Name & Middle Initial & Last Name or Official Title & Degree
Ji Hyun Lee, MD., Ph.D.
Phone
+82-10-9397-5694
Email
hidrleejh@dau.ac.kr
Facility Information:
Facility Name
Dong-A University
City
Busan
ZIP/Postal Code
602-713
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ji Hyun Lee, MD., Ph.D.
Phone
+82-10-9397-5694
Email
hidrleejh@dau.ac.kr
Facility Name
Keimyung University Dongsan Medical Center
City
Daegu
ZIP/Postal Code
700-712
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Young Rok Do, MD., Ph.D.
Phone
+82-10-3541-1160
Email
dyr1160@dsmc.or.kr

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
age,gender, disease type, stage, previous chemotherapy regimens, response to transplantation, patient survival, progression, toxicity profiles to the transpantation will be shared

Learn more about this trial

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

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