Chemoimmunotherapy and Allogeneic Stem Cell Transplant for NK T-cell Leukemia/Lymphoma
Study Details
Study Description
Brief 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.
Condition or Disease | Intervention/Treatment | Phase |
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Early Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Cohort 1 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. |
Drug: Methotrexate
Patients will receive methotrexate as part of chemoimmunotherapy regemin followed by allogeneic stem cell transplant.
Drug: Ifosfamide
Patients will receive Ifsofamide as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
Drug: Dexamethasone
Patients will receive dexamethasone as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
Drug: Etoposide
Patients will receive etoposide as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
Drug: calaspargase pegol
Patients will receive pegaspargase as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
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Experimental: Cohort 2 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. |
Drug: pralatraxate,
Patients will receive pralaxtraxate as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
Drug: cyclophosphamide
Patients will receive cyclophosphamide as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
Drug: Doxorubicin
Patients will receive doxorubicin as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
Drug: Prednisone
Patients will receive prednisone as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
Drug: Brentuximab Vedotin
Patients will receive brentuximab vedotin as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
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Outcome Measures
Primary Outcome Measures
- overall response rate [1 year]
to assess overall response rate following chemoimmunotherapy induction therapy
Secondary Outcome Measures
- event free survival [2 year]
to determine the event free survival after induction chemoimmunotherapy and allogeneic stem cell transplantation
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients must weigh at least 10 kilograms at the time of the study enrollment.
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Diagnosis
Newly diagnosed patients with histologically proven mature T- and NK- cell neoplasms:
COHORT 1
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Aggressive NK cell leukemia (ICD-O code 9948/3)
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Extranodal NK/T-cell lymphoma, nasal type (ICD-O code 9719/3) COHORT 2
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Enteropathy-associated T-cell lymphoma (ICD-O code 9717/3)
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Hepatosplenic T-cell lymphoma (ICD-O code 9716/3)
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Peripheral T-cell lymphoma, non-otherwise specified (ICD-O code 9702/3)
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Angioimmunoblastic T-cell lymphoma (ICD-O code 9705/3)
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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).
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Organ Function Requirements
Adequate liver function defined as:
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Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age.
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ALT (SGPT) < 3 x ULN for age.
Adequate cardiac function defined as:
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Shortening fraction of ≥ 27% by echocardiogram, or
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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:
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Alk+ or Alk- Anaplastic Large Cell Lymphoma (ALCL)
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Patients with active CNS disease.
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Patients with stage I or stage II disease (See Appendix III for Staging).
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Patients who have received any prior cytotoxic chemotherapy for the current diagnosis of NHL.
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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.
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Female patients who are pregnant. Pregnancy tests must be obtained in girls who are post menarchal.
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Lactating females, unless they have agreed not to breastfeed their infants.
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Patients with Down syndrome.
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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.
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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.
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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).
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | University of California San Francisco | San Francisco | California | United States | 94143 |
2 | New York Medical College | Valhalla | New York | United States | 10595 |
Sponsors and Collaborators
- New York Medical College
- University of Alabama at Birmingham
Investigators
- Study Director: Mitchell Cairo, MD, New York Medical College
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NYMC 575