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

Overview

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

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).