Chemoimmunotherapy and stem cell transplant for NK T-cell leukemia and lymphoma

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

This study is testing two different treatment combinations for people with advanced NK-cell leukemia and lymphoma to see which one works better before they receive a stem cell transplant.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 1 Year to 31 Years
• Sex: All
• Sponsor: New York Medical College (Academic / other)
• Drugs / interventions: chemotherapy, radiation, pembrolizumab, brentuximab, methotrexate, cyclophosphamide, doxorubicin, prednisone
• Locations: 6 sites (Birmingham, Alabama and 5 other locations)
• Trial ID: NCT03719105 on ClinicalTrials.gov

What this trial studies

This clinical trial involves two cohorts of patients with advanced stage NK-cell leukemia and lymphoma. Cohort 1 receives a modified chemotherapy regimen including dexamethasone, methotrexate, ifosfamide, pegaspargase, and etoposide, along with pembrolizumab. Cohort 2 combines pralatrexate and brentuximab vedotin with cyclophosphamide, doxorubicin, and prednisone. Both cohorts will proceed to allogeneic stem cell transplant based on their disease response.

Who should consider this trial

Good fit: Ideal candidates include children, adolescents, and young adults with newly diagnosed advanced stage NK-cell or peripheral T-cell malignancies.

Not a fit: Patients with early-stage disease or those with non-mature T- and NK-cell neoplasms may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes for patients with aggressive NK-cell and peripheral T-cell malignancies.

How similar studies have performed: While similar approaches have been explored, this specific combination of therapies in this patient population is novel.

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).

Where this trial is running

Birmingham, Alabama and 5 other locations

• University of Alabama — Birmingham, Alabama, United States (Recruiting)
• Children's Hospital Orange County — Orange, California, United States (Recruiting)
• University of California San Francisco — San Francisco, California, United States (Recruiting)
• Helen De Vos — Grand Rapids, Michigan, United States (Recruiting)
• New York Medical College — Valhalla, New York, United States (Recruiting)
• Nationwide Children's Hospital — Columbus, Ohio, United States (Recruiting)

Study contacts

• Study coordinator: Ana Xavier

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