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

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

Primary outcomes

• overall response rate [1 year]: to assess overall response rate following chemoimmunotherapy induction therapy

Secondary outcomes

• event free survival [2 year]: to determine the event free survival after induction chemoimmunotherapy and allogeneic stem cell transplantation

Sex: All, ages: 1 Year to 31 Years

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).

• Mitchell Cairo, MD, Study director, New York Medical College