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

Sponsor
New York Medical College (Other)
Overall Status
Recruiting
CT.gov ID
NCT03719105
Collaborator
University of Alabama at Birmingham (Other)
40
2
2
58
20
0.3

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
40 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Cohort 1 and 2 will be based on initial diagnosis.Cohort 1 and 2 will be based on initial diagnosis.
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Mar 1, 2019
Anticipated Primary Completion Date :
Dec 31, 2022
Anticipated Study Completion Date :
Dec 31, 2023

Arms and Interventions

Arm Intervention/Treatment
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.

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.

Outcome Measures

Primary Outcome Measures

  1. overall response rate [1 year]

    to assess overall response rate following chemoimmunotherapy induction therapy

Secondary Outcome Measures

  1. event free survival [2 year]

    to determine the event free survival after induction chemoimmunotherapy and allogeneic stem cell transplantation

Eligibility Criteria

Criteria

Ages Eligible for Study:
1 Year to 31 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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).

Contacts and Locations

Locations

Site City State Country Postal Code
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.
Responsible Party:
Mitchell Cairo, Executive Vice-Chair, New York Medical College
ClinicalTrials.gov Identifier:
NCT03719105
Other Study ID Numbers:
  • NYMC 575
First Posted:
Oct 25, 2018
Last Update Posted:
Sep 2, 2021
Last Verified:
Sep 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Sep 2, 2021