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

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

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.


Condition or disease Intervention/treatment Phase
NK-Cell Lymphoma NK-Cell Leukemia Peripheral T Cell Lymphoma Drug: Methotrexate Drug: pralatraxate, Drug: Ifosfamide Drug: Dexamethasone Drug: Etoposide Drug: Pegaspargase Drug: cyclophosphamide Drug: Doxorubicin Drug: Prednisone Drug: Brentuximab Vedotin Early Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
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
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
Actual Study Start Date : March 1, 2019
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2023


Arm Intervention/treatment
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.

Drug: Methotrexate
Patients will receive methotrexate as part of chemoimmunotherapy regemin 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.

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.

Drug: pralatraxate,
Patients will receive pralaxtraxate 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.




Primary Outcome Measures :
  1. overall response rate [ Time Frame: 1 year ]
    to assess overall response rate following chemoimmunotherapy induction therapy


Secondary Outcome Measures :
  1. event free survival [ Time Frame: 2 year ]
    to determine the event free survival after induction chemoimmunotherapy and allogeneic stem cell transplantation



Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 31 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03719105


Contacts
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Contact: Ana Xavier (205) 638-6763 axavier@peds.uab.edu
Contact: Lauren Harrison 6172857844 lauren_harrison@nymc.edu

Locations
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United States, New York
New York Medical College Recruiting
Valhalla, New York, United States, 10595
Contact: Mitchell Cairo, MD    914-594-3650    mitchell_cairo@nymc.edu   
Contact: Lauren Harrison, MSN    617-285-7844    lauren_harrison@nymc.edu   
Sponsors and Collaborators
New York Medical College
University of Alabama at Birmingham
Investigators
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Study Director: Mitchell Cairo, MD New York Medical College

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Responsible Party: Mitchell Cairo, Executive Vice-Chair, New York Medical College
ClinicalTrials.gov Identifier: NCT03719105     History of Changes
Other Study ID Numbers: NYMC 575
First Posted: October 25, 2018    Key Record Dates
Last Update Posted: March 14, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Lymphoma, T-Cell, Peripheral
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, T-Cell
Lymphoma, Non-Hodgkin
Dexamethasone
Dexamethasone acetate
Prednisone
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Methotrexate
Etoposide
Etoposide phosphate
Ifosfamide
Isophosphamide mustard
Pegaspargase
BB 1101
Antibodies, Monoclonal
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs