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

August 17, 2022 updated by: Young Rok Do, Keimyung University Dongsan Medical Center

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

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.

Study Overview

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 Type

Interventional

Enrollment (Anticipated)

34

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

      • Busan, Korea, Republic of, 602-713
        • Recruiting
        • Dong-A University
        • Contact:
      • Daegu, Korea, Republic of, 700-712
        • Recruiting
        • Keimyung University Dongsan Medical Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
2-year progression-free survival
Time Frame: 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.
2 years

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

December 1, 2016

Primary Completion (ANTICIPATED)

December 1, 2025

Study Completion (ANTICIPATED)

December 1, 2027

Study Registration Dates

First Submitted

August 4, 2016

First Submitted That Met QC Criteria

August 8, 2016

First Posted (ESTIMATE)

August 9, 2016

Study Record Updates

Last Update Posted (ACTUAL)

August 18, 2022

Last Update Submitted That Met QC Criteria

August 17, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

age,gender, disease type, stage, previous chemotherapy regimens, response to transplantation, patient survival, progression, toxicity profiles to the transpantation will be shared

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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