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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• 2-year progression-free survival [Срок оценки: 2 years]

Вторичные конечные точки (10)

• Response rate [Срок оценки: 3-months]
• Time to neutrophil engraftment [Срок оценки: Day 30]
• Time to platelet engraftment [Срок оценки: Day 30]
• 2-year overall survival [Срок оценки: 2 years]
• 100-days treatment-related mortality [Срок оценки: Days 100]
• Rate of regimen-related toxicities [Срок оценки: Day 30]
• Rate of hepatic venoocclusive disease (HVOD) [Срок оценки: Day 30]
• Acute graft-versus-host disease (GVHD) grades I-IV [Срок оценки: Day 100]
• Chronic GVHD grades I-IV [Срок оценки: 2 year]
• Rate of cytomegalovirus (CMV) infection [Срок оценки: 2 year]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

South Korea · 2 центра

• Dong-A University — Busan
• Keimyung University Dongsan Medical Center — Daegu

Идентификаторы

NCT: NCT02859402 · DSMC 2016-05-051

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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