Chemoimmunotherapy and Allogeneic Stem Cell Transplant for NK T-cell Leukemia/Lymphoma

Официальное название

Pilot Study Using Induction Chemo-immunotherapy Followed by Consolidation With Reduced Toxicity Conditioning and Allogenic Stem Cell Transplant in Advanced Stage Mature Non-anaplastic T-Cell or NK Lymphoma/Leukemia in Children, Adolescents and Young Adults; A NK/T-Cell Lymphoma/Leukemia Consortium Study

Обзор

Patients are in 2 cohorts: Cohort 1: dexamethasone, methotrexate, ifosfamide, pegaspargase, and etoposide (modified SMILE) chemotherapy regimen alone and pembrolizumab in children, adolescents, and young adults with advanced stage NK lymphoma and leukemia Cohort 2: combining pralatrexate (PRX) (Cycles 1, 2, 4, 6) and brentuximab vedotin (BV) (Cycles 3, 5) to cyclophosphamide, doxorubicin, and prednisone in children, adolescent, and young adults with advanced peripheral T-cell lymphoma (non-anaplastic large cell lymphoma or non-NK lymphoma/leukemia) . Both groups proceed to allogeneic stem cell transplant with disease response.

Вмешательства

• Препарат Methotrexate
  Patients will receive methotrexate as part of chemoimmunotherapy regemin followed by allogeneic stem cell transplant.
• Препарат pralatraxate,
  Patients will receive pralaxtraxate as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
• Препарат Ifosfamide
  Patients will receive Ifsofamide as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
• Препарат Dexamethasone
  Patients will receive dexamethasone as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
• Препарат Etoposide
  Patients will receive etoposide as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
• Препарат calaspargase pegol
  Patients will receive pegaspargase as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
• Препарат cyclophosphamide
  Patients will receive cyclophosphamide as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
• Препарат Doxorubicin
  Patients will receive doxorubicin as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
• Препарат Prednisone
  Patients will receive prednisone as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
• Препарат Brentuximab Vedotin
  Patients will receive brentuximab vedotin as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.

Первичные конечные точки

• overall response rate [Срок оценки: 1 year]

Вторичные конечные точки (1)

• event free survival [Срок оценки: 2 year]

Критерии участия

Критерии включения

• Patients must weigh at least 10 kilograms at the time of the study enrollment.
• Diagnosis

Newly diagnosed patients with histologically proven mature T- and NK- cell neoplasms:

COHORT 1

• Aggressive NK cell leukemia (ICD-O code 9948/3)
• Extranodal NK/T-cell lymphoma, nasal type (ICD-O code 9719/3) COHORT 2
• Enteropathy-associated T-cell lymphoma (ICD-O code 9717/3)
• Hepatosplenic T-cell lymphoma (ICD-O code 9716/3)
• Peripheral T-cell lymphoma, non-otherwise specified (ICD-O code 9702/3)
• Angioimmunoblastic T-cell lymphoma (ICD-O code 9705/3)
• Other mature T- and NK-cell neoplasm histologies will considered after case-by-case discussion with Study Chairs and executive Vice-Chair Patients with lymphoma must have stage III or IV disease (See Appendix III for Staging).

• Organ Function Requirements

Adequate liver function defined as:

• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age.
• ALT (SGPT) < 3 x ULN for age.

Adequate cardiac function defined as:

• Shortening fraction of ≥ 27% by echocardiogram, or
• Ejection fraction of ≥ 50% by radionuclide angiogram.

Adequate pulmonary function defined as:

• Patients with a history of pulmonary dysfunction must have no evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficiency, and a pulse oximetry > 92% while breathing room air unless current dysfunction is due to the lymphoma, in which case the patient is eligible.

Критерии исключения

• Alk+ or Alk- Anaplastic Large Cell Lymphoma (ALCL)
• Patients with active CNS disease.
• Patients with stage I or stage II disease (See Appendix III for Staging).
• Patients who have received any prior cytotoxic chemotherapy for the current diagnosis of NHL.
• Previous steroid treatment and/or radiation treatment are not allowed unless they are used for emergency management. Patients who have received emergency irradiation and/or steroid therapy will be eligible only if started on protocol therapy not more than one week from the start of radiotherapy or steroids.
• Female patients who are pregnant. Pregnancy tests must be obtained in girls who are post menarchal.
• Lactating females, unless they have agreed not to breastfeed their infants.
• Patients with Down syndrome.
• Patients taking CYP3A4 substrates with narrow therapeutic indices. Patients (COHORT 2 ONLY) chronically receiving medications known to be metabolized by CYP3A4 and with narrow therapeutic indices (See Appendix V). The topical use of these medications (if applicable) is allowed.
• Patients taking CYP3A4 inhibitors. Patients (COHORT 2 ONLY) chronically receiving drugs that are known potent CYP3A4 inhibitors within 7 days prior to study enrollment (See Appendix V). The topical use of these medications (if applicable) is allowed.
• Patients taking CYP3A4 inducers. Patients (COHORT 2 ONLY) chronically receiving drugs that are known potent CYP3A4 inducers within 12 days prior to study enrollment (See Appendix V).

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 6 центров

• University of Alabama — Birmingham
• Children's Hospital Orange County — Orange
• University of California San Francisco — San Francisco
• Helen De Vos — Grand Rapids
• New York Medical College — Valhalla
• Nationwide Children's Hospital — Columbus

Идентификаторы

NCT: NCT03719105 · NYMC 575

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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