- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03719105
Chemoimmunotherapy and Allogeneic Stem Cell Transplant for NK T-cell Leukemia/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
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.
Study Overview
Status
Study Type
Enrollment (Estimated)
Phase
- Early Phase 1
Contacts and Locations
Study Contact
- Name: Ana Xavier
- Phone Number: (205) 638-6763
- Email: axavier@peds.uab.edu
Study Contact Backup
- Name: Lauren Harrison
- Phone Number: 6172857844
- Email: lauren_harrison@nymc.edu
Study Locations
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Alabama
-
Birmingham, Alabama, United States, 35223
- Recruiting
- University of Alabama
-
Contact:
- Ana Xavier, MD
- Email: axavier@peds.uab.edu
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California
-
Orange, California, United States, 92968
- Recruiting
- Children's Hospital Orange County
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Contact:
- Carol Lin, MD
- Email: clin@choc.org
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San Francisco, California, United States, 94143
- Recruiting
- University of California San Francisco
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Contact:
- MIchelle Hermiston, MD
- Email: michelle.hermiston@ucsf.edu
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Michigan
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Grand Rapids, Michigan, United States, 49503
- Recruiting
- Helen De Vos
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Contact:
- Troy Quigg, MD
- Email: troy.quigg@spectrumhealth.org
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New York
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Valhalla, New York, United States, 10595
- Recruiting
- New York Medical College
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Contact:
- Mitchell Cairo, MD
- Phone Number: 914-594-3650
- Email: mitchell_cairo@nymc.edu
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Contact:
- Lauren Harrison, MSN
- Phone Number: 617-285-7844
- Email: lauren_harrison@nymc.edu
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Ohio
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Columbus, Ohio, United States, 43205
- Recruiting
- Nationwide Children's Hospital
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Contact:
- Anthony Audino, MD
- Email: Anthony.Audino@nationwidechildrens.org
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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, calaspargase pegol 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. |
Patients will receive methotrexate as part of chemoimmunotherapy regemin followed by allogeneic stem cell transplant.
Patients will receive Ifsofamide as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
Patients will receive dexamethasone as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
Patients will receive etoposide as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
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. |
Patients will receive pralaxtraxate as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
Patients will receive cyclophosphamide as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
Patients will receive doxorubicin as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
Patients will receive prednisone as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
Patients will receive brentuximab vedotin as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
overall response rate
Time Frame: 1 year
|
to assess overall response rate following chemoimmunotherapy induction therapy
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
event free survival
Time Frame: 2 year
|
to determine the event free survival after induction chemoimmunotherapy and allogeneic stem cell transplantation
|
2 year
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Mitchell Cairo, MD, New York Medical College
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Lymphoma
- Leukemia
- Lymphoma, T-Cell
- Lymphoma, T-Cell, Peripheral
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Antineoplastic Agents, Immunological
- Dermatologic Agents
- Antibiotics, Antineoplastic
- Reproductive Control Agents
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Immunoconjugates
- Immunotoxins
- Dexamethasone
- Cyclophosphamide
- Etoposide
- Ifosfamide
- Prednisone
- Doxorubicin
- Methotrexate
- Brentuximab Vedotin
Other Study ID Numbers
- NYMC 575
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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