Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 17 of 19 for:    pralatrexate AND PTCL

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE October 23, 2018
First Posted Date  ICMJE October 25, 2018
Last Update Posted Date March 14, 2019
Actual Study Start Date  ICMJE March 1, 2019
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 23, 2018)
overall response rate [ Time Frame: 1 year ]
to assess overall response rate following chemoimmunotherapy induction therapy
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03719105 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Chemoimmunotherapy and Allogeneic Stem Cell Transplant for NK T-cell Leukemia/Lymphoma
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE 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  ICMJE
  • NK-Cell Lymphoma
  • NK-Cell Leukemia
  • Peripheral T Cell Lymphoma
Intervention  ICMJE
  • 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  ICMJE
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 23, 2018)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2023
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 31 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Ana Xavier (205) 638-6763 axavier@peds.uab.edu
Contact: Lauren Harrison 6172857844 lauren_harrison@nymc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03719105
Other Study ID Numbers  ICMJE 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  ICMJE
Plan to Share IPD: No
Responsible Party Mitchell Cairo, New York Medical College
Study Sponsor  ICMJE New York Medical College
Collaborators  ICMJE University of Alabama at Birmingham
Investigators  ICMJE
Study Director: Mitchell Cairo, MD New York Medical College
PRS Account New York Medical College
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP