Clinical trial NCT02859402: Allogeneic Stem Cell Transplantation in Relapsed/Refractory T-, NK/T-cell Lymphomas
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
Overall status: RECRUITING
Phase: PHASE2
Conditions: 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
Lead sponsor: Keimyung University Dongsan Medical Center
Sponsor class: OTHER
Collaborators: name: Otsuka Pharmaceutical Co., Ltd.
First posted: 2016-08-09
Enrollment: 34
Sex: ALL
Minimum age (years): 19
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 2-year progression-free survival
timeFrame: 2 years
Secondary outcomes:
measure: Response rate
timeFrame: 3-months
measure: Time to neutrophil engraftment
timeFrame: Day 30
measure: Time to platelet engraftment
timeFrame: Day 30
measure: 2-year overall survival
timeFrame: 2 years
measure: 100-days treatment-related mortality
timeFrame: Days 100
measure: Rate of regimen-related toxicities
timeFrame: Day 30
measure: Rate of hepatic venoocclusive disease (HVOD)
timeFrame: Day 30
measure: Acute graft-versus-host disease (GVHD) grades I-IV
timeFrame: Day 100
measure: Chronic GVHD grades I-IV
timeFrame: 2 year
measure: Rate of cytomegalovirus (CMV) infection
timeFrame: 2 year
Other outcomes:
Locations:
city: Busan
country: Korea, Republic of
facility: Dong-A University
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
Study officials:
References: