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

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).