Chemoimmunotherapy and Allogeneic Stem Cell Transplant for NK T-cell Leukemia/Lymphoma
NK-Cell Lymphoma, NK-Cell Leukemia, Peripheral T Cell Lymphoma
About this trial
This is an interventional treatment trial for NK-Cell Lymphoma
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).
Sites / Locations
- University of California San FranciscoRecruiting
- New York Medical CollegeRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Cohort 1
Cohort 2
Patients with aggressive NK cell leukemia or stage III or IV extranodal NK/T-cell lymphoma, nasal type. Chemotherapy Regimen: mSMILE: Methotrexate Day 1, Ifosfamide Days 2-4, Dexamethasone Days 2-4, Etoposide Days 2-4, calaspargase pegol Day 8. For patients in CR and no available allogeneic SCT can receive up to 2 additional cycles of mSMILE. Pembrolizumab: For patients in PR/MR/NR/PD after 2 cycles of mSMILE. Allogeneic Stem Cell Transplant if donor available and not in PD.
Patients with stage III or IV peripheral T-cell lymphoma-NOS, angioimmunoblastic T-cell lymphoma, hepatosplenic T-cell lymphoma, or enteropathy-associated T-cell lymphoma (other histologies will be considered after case-by-case discussion with Study Chairs and Executive Vice-Chairs). Chemotherapy Regimen: Cycle 1 & 2: Pralatrexate Days 1, 8, and 15, cyclophosphamide Day 1, DOXOrubicin Day 1, predniSONE days 1-5 Cycle 3 & 5: Brentuximab vedotin Day 1, cyclophosphamide Day 1, DOXOrubicin Day 1, predniSONE days 1-5 Cycle 4 & 6: Pralatrexate Days 1, 8, and 15, cyclophosphamide Day 1, DOXOrubicin Day 1, predniSONE days 1-5 Allogeneic Stem Cell Transplant if donor available and not in PD.