Recruiting
Early Phase 1

Dexamethasone & Pembrolizumab, PRX & BV

Sponsor:

New York Medical College

Code:

NCT03719105

Conditions

NK-Cell Lymphoma

NK-Cell Leukemia

Peripheral T Cell Lymphoma

Eligibility Criteria

Sex: All

Age: 1 - 31

Healthy Volunteers: Not accepted

Interventions

Methotrexate

pralatraxate,

Ifosfamide

Dexamethasone

Etoposide

Study Details

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

Study ID

NCT03719105

Start date

Mar 1, 2019

Status verified date

Aug, 2026

Completion date

Dec 31, 2028

Anticipated

Primary completion date

Dec 31, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 1 - 31

Healthy Volunteers: Not accepted

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).

Study Design

Enrollment

40 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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.

Interventions

Methotrexate

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

pralatraxate,

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

Ifosfamide

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

Dexamethasone

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

Etoposide

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

calaspargase pegol

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

cyclophosphamide

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

Doxorubicin

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

Prednisone

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

Brentuximab Vedotin

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

Primary outcome measure

  • overall response rate [ Time Frame: 1 year ]

Central Contacts and Locations

Central contacts

Ana Xavier

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

Lauren Harrison

6172857844lauren_harrison@nymc.edu

Locations

University of Alabama

Recruiting

Birmingham, Alabama, United States, 35223

Contacts

Ana Xavier, MD

axavier@peds.uab.edu

Children's Hospital Orange County

Recruiting

Orange, California, United States, 92968

Contacts

Carol Lin, MD

clin@choc.org

University of California San Francisco

Recruiting

San Francisco, California, United States, 94143

Contacts

Rohini Jain, MD

877-827-3222cancertrials@ucsf.edu

Helen De Vos

Recruiting

Grand Rapids, Michigan, United States, 49503

Contacts

Troy Quigg, MD

troy.quigg@spectrumhealth.org

New York Medical College

Recruiting

Valhalla, New York, United States, 10595

Contacts

Mitchell Cairo, MD

914-594-3650mitchell_cairo@nymc.edu

Lauren Harrison, MSN

617-285-7844lauren_harrison@nymc.edu

Nationwide Children's Hospital

Recruiting

Columbus, Ohio, United States, 43205

Contacts

Anthony Audino, MD

Anthony.Audino@nationwidechildrens.org

More Information

Sponsor

New York Medical College

Last update posted

Aug 18, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by New York Medical College on 2026-08-18.