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

• ClinicalTrials.gov Identifier: NCT03719105
• Recruitment Status: Recruiting
• First Posted: October 25, 2018
• Last Update Posted: March 14, 2019
• Sponsor: New York Medical College
• Collaborator: University of Alabama at Birmingham
• Information provided by (Responsible Party): Mitchell Cairo, New York Medical College

Tracking Information

• First Submitted Date: October 23, 2018
• First Posted Date: October 25, 2018
• Last Update Posted Date: March 14, 2019
• Actual Study Start Date: March 1, 2019
• Estimated Primary Completion Date: December 31, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 23, 2018)

overall response rate [ Time Frame: 1 year ]

to assess overall response rate following chemoimmunotherapy induction therapy

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT03719105 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: October 23, 2018)

event free survival [ Time Frame: 2 year ]

to determine the event free survival after induction chemoimmunotherapy and allogeneic stem cell transplantation

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Chemoimmunotherapy and Allogeneic Stem Cell Transplant for NK T-cell Leukemia/Lymphoma
• Official Title: Induction Chemo-Immunotherapy Followed by Reduced Toxicity Conditioning and Allogeneic Stem Cell Transplant in Advanced Stage Mature Non-anaplastic T-cell or NK Lymphoma/Leukemia

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Early Phase 1

Study Design

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Cohort 1 and 2 will be based on initial diagnosis.

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

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

Intervention

• Drug: Methotrexate
  Patients will receive methotrexate as part of chemoimmunotherapy regemin followed by allogeneic stem cell transplant.
• Drug: pralatraxate,
  Patients will receive pralaxtraxate as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
• Drug: Ifosfamide
  Patients will receive Ifsofamide as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
• Drug: Dexamethasone
  Patients will receive dexamethasone as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
• Drug: Etoposide
  Patients will receive etoposide as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
• Drug: Pegaspargase
  Patients will receive pegaspargase as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
• Drug: cyclophosphamide
  Patients will receive cyclophosphamide as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
• Drug: Doxorubicin
  Patients will receive doxorubicin as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
• Drug: Prednisone
  Patients will receive prednisone as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
• Drug: Brentuximab Vedotin
  Patients will receive brentuximab vedotin as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.

Study 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, Pegaspargase 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.

  Interventions:

  • Drug: Methotrexate
  • Drug: Ifosfamide
  • Drug: Dexamethasone
  • Drug: Etoposide
  • Drug: Pegaspargase
• 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:

  • Drug: pralatraxate,
  • Drug: cyclophosphamide
  • Drug: Doxorubicin
  • Drug: Prednisone
  • Drug: Brentuximab Vedotin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 23, 2018): 40
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2023
• Estimated Primary Completion Date: December 31, 2022 (Final data collection date for primary outcome measure)

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year to 31 Years (Child, Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Ana Xavier; (205) 638-6763; axavier@peds.uab.edu

Contact: Lauren Harrison; 6172857844; lauren_harrison@nymc.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03719105
• Other Study ID Numbers: NYMC 575
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Mitchell Cairo, New York Medical College
• Study Sponsor: New York Medical College
• Collaborators: University of Alabama at Birmingham

Investigators

• Study Director: Mitchell Cairo, MD; New York Medical College

• PRS Account: New York Medical College
• Verification Date: March 2019