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

NCT ID: NCT03719105

Last Updated: 2025-08-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-01
• Study Completion Date: 2028-12-31

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 Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Methotrexate

Intervention Type: DRUG

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

Ifosfamide

Intervention Type: DRUG

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

Dexamethasone

Intervention Type: DRUG

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

Etoposide

Intervention Type: DRUG

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

calaspargase pegol

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

pralatraxate,

Intervention Type: DRUG

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

cyclophosphamide

Intervention Type: DRUG

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

Doxorubicin

Intervention Type: DRUG

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

Prednisone

Intervention Type: DRUG

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

Brentuximab Vedotin

Intervention Type: DRUG

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

Interventions

Methotrexate

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

Intervention Type: DRUG

pralatraxate,

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

Intervention Type: DRUG

Ifosfamide

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

Intervention Type: DRUG

Dexamethasone

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

Intervention Type: DRUG

Etoposide

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

Intervention Type: DRUG

calaspargase pegol

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

Intervention Type: DRUG

cyclophosphamide

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

Intervention Type: DRUG

Doxorubicin

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

Intervention Type: DRUG

Prednisone

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

Intervention Type: DRUG

Brentuximab Vedotin

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

Intervention Type: DRUG

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).

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 31 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Alabama at Birmingham

OTHER

Sponsor Role: collaborator

New York Medical College

OTHER

Sponsor Role: lead

Responsible Party

Mitchell Cairo

Executive Vice-Chair

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mitchell Cairo, MD

Role: STUDY_DIRECTOR

New York Medical College

Locations

University of Alabama

Birmingham, Alabama, United States

Site Status: RECRUITING

Children's Hospital Orange County

Orange, California, United States

Site Status: RECRUITING

University of California San Francisco

San Francisco, California, United States

Site Status: RECRUITING

Helen De Vos

Grand Rapids, Michigan, United States

Site Status: RECRUITING

New York Medical College

Valhalla, New York, United States

Site Status: RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Ana Xavier

Role: CONTACT

axavier@peds.uab.edu

(205) 638-6763

Lauren Harrison

Role: CONTACT

lauren_harrison@nymc.edu

6172857844

Facility Contacts

Ana Xavier, MD

Role: primary

axavier@peds.uab.edu

Carol Lin, MD

Role: primary

clin@choc.org

MIchelle Hermiston, MD

Role: primary

michelle.hermiston@ucsf.edu

Troy Quigg, MD

Role: primary

troy.quigg@spectrumhealth.org

Mitchell Cairo, MD

Role: primary

mitchell_cairo@nymc.edu

914-594-3650

Lauren Harrison, MSN

Role: backup

lauren_harrison@nymc.edu

617-285-7844

Anthony Audino, MD

Role: primary

Anthony.Audino@nationwidechildrens.org

Other Identifiers

NYMC 575

Identifier Type: -

Identifier Source: org_study_id