chemoimmunotherapy and allogeneic stem cell transplant for nk t-cell leukemia/lymphoma

Conditions: NK-Cell Lymphoma; NK-Cell Leukemia; Peripheral T Cell Lymphoma

Summary: 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.


Eligibility criteria:
inclusion criteria: * 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. exclusion criteria: * 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).