Clinical Trials /

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

NCT03719105

Description:

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.

Related Conditions:
  • Aggressive NK-Cell Leukemia
  • Angioimmunoblastic T-Cell Lymphoma
  • Enteropathy-Associated T-Cell Lymphoma
  • Hepatosplenic T-Cell Lymphoma
  • Nasal Type Extranodal NK/T-Cell Lymphoma
  • Peripheral T-Cell Lymphoma, Not Otherwise Specified
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Chemoimmunotherapy and Allogeneic Stem Cell Transplant for NK T-cell Leukemia/Lymphoma
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: NYMC 575
  • NCT ID: NCT03719105

Conditions

  • NK-Cell Lymphoma
  • NK-Cell Leukemia
  • Peripheral T Cell Lymphoma

Interventions

DrugSynonymsArms
MethotrexateCohort 1
pralatraxate,Cohort 2
IfosfamideCohort 1
DexamethasoneCohort 1
EtoposideCohort 1
calaspargase pegolCohort 1
cyclophosphamideCohort 2
DoxorubicinCohort 2
PrednisoneCohort 2
Brentuximab VedotinCohort 2

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Cohort 1ExperimentalPatients 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.
  • Methotrexate
  • Ifosfamide
  • Dexamethasone
  • Etoposide
  • calaspargase pegol
Cohort 2ExperimentalPatients 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.
  • pralatraxate,
  • cyclophosphamide
  • Doxorubicin
  • Prednisone
  • Brentuximab Vedotin

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).
      
Maximum Eligible Age:31 Years
Minimum Eligible Age:1 Year
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:overall response rate
Time Frame:1 year
Safety Issue:
Description:to assess overall response rate following chemoimmunotherapy induction therapy

Secondary Outcome Measures

Measure:event free survival
Time Frame:2 year
Safety Issue:
Description:to determine the event free survival after induction chemoimmunotherapy and allogeneic stem cell transplantation

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:New York Medical College

Last Updated

February 26, 2020