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

NCT03719105 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: NYMC 575
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 6

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.

Conditions

NK-Cell Lymphoma; NK-Cell Leukemia; Peripheral T Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• overall response rate

  to assess overall response rate following chemoimmunotherapy induction therapy

  1 year

Secondary Outcomes (1)

• event free survival

  2 year

Study Arms (2)

Cohort 1

EXPERIMENTAL

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; Drug: Ifosfamide; Drug: Dexamethasone; Drug: Etoposide; Drug: calaspargase pegol

Cohort 2

EXPERIMENTAL

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,; Drug: cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone; Drug: Brentuximab Vedotin

Interventions

Methotrexate DRUG

Patients will receive methotrexate as part of chemoimmunotherapy regemin followed by allogeneic stem cell transplant.

Cohort 1

pralatraxate, DRUG

Patients will receive pralaxtraxate as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.

Cohort 2

Ifosfamide DRUG

Patients will receive Ifsofamide as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.

Cohort 1

Dexamethasone DRUG

Patients will receive dexamethasone as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.

Cohort 1

Etoposide DRUG

Patients will receive etoposide as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.

Cohort 1

calaspargase pegol DRUG

Patients will receive pegaspargase as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.

Cohort 1

cyclophosphamide DRUG

Patients will receive cyclophosphamide as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.

Cohort 2

Doxorubicin DRUG

Patients will receive doxorubicin as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.

Cohort 2

Prednisone DRUG

Patients will receive prednisone as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.

Cohort 2

Brentuximab Vedotin DRUG

Patients will receive brentuximab vedotin as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.

Cohort 2

Eligibility Criteria

• Age: 1 Year - 31 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• New York Medical College: lead
• University of Alabama at Birmingham: collaborator

Study Sites (6)

University of Alabama

Birmingham, Alabama, 35223, United States

RECRUITING

Children's Hospital Orange County

Orange, California, 92968, United States

RECRUITING

University of California San Francisco

San Francisco, California, 94143, United States

RECRUITING

Helen De Vos

Grand Rapids, Michigan, 49503, United States

RECRUITING

New York Medical College

Valhalla, New York, 10595, United States

RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Large Granular Lymphocytic; Lymphoma, T-Cell, Peripheral

Interventions

Methotrexate; Ifosfamide; Dexamethasone; Etoposide; calaspargase pegol; Cyclophosphamide; Doxorubicin; Prednisone; Brentuximab Vedotin

Condition Hierarchy (Ancestors)

Leukemia, T-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Glucosides; Glycosides; Carbohydrates; Daunorubicin; Anthracyclines; Naphthacenes; Aminoglycosides; Pregnadienediols; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Study Officials

• Mitchell Cairo, MD

  New York Medical College

  STUDY DIRECTOR

Central Study Contacts

Ana Xavier

CONTACT

(205) 638-6763; axavier@peds.uab.edu

Lauren Harrison

CONTACT

6172857844; lauren_harrison@nymc.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Executive Vice-Chair

Model Details: Cohort 1 and 2 will be based on initial diagnosis.

Study Record Dates

• First Submitted: October 23, 2018
• First Posted: October 25, 2018
• Study Start: March 1, 2019
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: August 8, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)