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.

Full Title of Study: “Induction Chemo-Immunotherapy Followed by Reduced Toxicity Conditioning and Allogeneic Stem Cell Transplant in Advanced Stage Mature Non-anaplastic T-cell or NK Lymphoma/Leukemia”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 31, 2022

Interventions

  • Drug: Methotrexate
    • Patients will receive methotrexate as part of chemoimmunotherapy regemin followed by allogeneic stem cell transplant.
  • Drug: pralatraxate,
    • Patients will receive pralaxtraxate as part of chemoimmunotherapy regimen 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.
  • 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.

Arms, Groups and Cohorts

  • 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.
  • 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.

Clinical Trial Outcome Measures

Primary Measures

  • overall response rate
    • Time Frame: 1 year
    • to assess overall response rate following chemoimmunotherapy induction therapy

Secondary Measures

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

Participating in This Clinical Trial

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).

Gender Eligibility: All

Minimum Age: 1 Year

Maximum Age: 31 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • New York Medical College
  • Collaborator
    • University of Alabama at Birmingham
  • Provider of Information About this Clinical Study
    • Principal Investigator: Mitchell Cairo, Executive Vice-Chair – New York Medical College
  • Overall Official(s)
    • Mitchell Cairo, MD, Study Director, New York Medical College
  • Overall Contact(s)
    • Ana Xavier, (205) 638-6763, axavier@peds.uab.edu

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