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

Peripheral T Cell Lymphoma Clinical Trial

Official title:

Pilot Study Using Induction Chemo-immunotherapy Followed by Consolidation With Reduced Toxicity Conditioning and Allogenic Stem Cell Transplant in Advanced Stage Mature Non-anaplastic T-Cell or NK Lymphoma/Leukemia in Children, Adolescents and Young Adults; A NK/T-Cell Lymphoma/Leukemia Consortium Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03719105
• Other study ID #: NYMC 575
• Status: Recruiting
• Phase: Early Phase 1
• Start date: March 1, 2019
• Est. completion date: December 31, 2026

Study information

• Verified date: October 2023
• Source: New York Medical College
• Contact: Ana Xavier
• Phone: (205) 638-6763
• Email: axavier[@]peds.uab.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 31 Years

Eligibility

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).

Related Conditions & MeSH terms

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

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
United States	University of Alabama	Birmingham	Alabama
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Helen De Vos	Grand Rapids	Michigan
United States	Children's Hospital Orange County	Orange	California
United States	University of California San Francisco	San Francisco	California
United States	New York Medical College	Valhalla	New York

Sponsors (2)

Lead Sponsor	Collaborator
New York Medical College	University of Alabama at Birmingham

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	overall response rate	to assess overall response rate following chemoimmunotherapy induction therapy	1 year
Secondary	event free survival	to determine the event free survival after induction chemoimmunotherapy and allogeneic stem cell transplantation	2 year