NK-Cell LymphomaEarly Phase 1NCT03719105
Chemoimmunotherapy and Allogeneic Stem Cell Transplant for NK T-cell Leukemia/Lymphoma
A Early Phase 1 study testing Methotrexate, pralatraxate, and Ifosfamide in people with NK-Cell Lymphoma and NK-Cell Leukemia, run by New York Medical College at 6 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 1 year to 31 years
- Conditions the study is for
- NK-Cell Lymphoma, NK-Cell Leukemia, Peripheral T Cell Lymphoma
- What is being tested?
- Methotrexate, pralatraxate, and Ifosfamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 6 sitesUnited States
- Study dates
- 1 Mar 2019to 31 Dec 2028
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 31 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Show all 20Show fewer
- 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.
Who cannot join
- 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.
Show all 11Show fewer
- 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).
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
United States6 sites, 6 recruiting
- Recruiting
University of Alabama
Birmingham, Alabama, 35223
Ana Xavier, MD, axavier@peds.uab.edu
- Recruiting
Nationwide Children's Hospital
Columbus, Ohio, 43205
Anthony Audino, MD, Anthony.Audino@nationwidechildrens.org
- Recruiting
Helen De Vos
Grand Rapids, Michigan, 49503
Troy Quigg, MD, troy.quigg@spectrumhealth.org
- Recruiting
Children's Hospital Orange County
Orange, California, 92968
Carol Lin, MD, clin@choc.org
- Recruiting
University of California San Francisco
San Francisco, California, 94143
Rohini Jain, MD, 877-827-3222, cancertrials@ucsf.edu
- Recruiting
New York Medical College
Valhalla, New York, 10595
Mitchell Cairo, MD, 914-594-3650, mitchell_cairo@nymc.edu
Lauren Harrison, MSN, 617-285-7844, lauren_harrison@nymc.edu
About this study
Official title: 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.
- Being tested
- Methotrexate, pralatraxate,, Ifosfamide, Dexamethasone, Etoposide
- Medical subject headings
- Leukemia, Large Granular Lymphocytic, Lymphoma, T-Cell, Peripheral
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethotrexateDrug
Patients will receive methotrexate as part of chemoimmunotherapy regemin followed by allogeneic stem cell transplant.
pralatraxate,Drug
Patients will receive pralaxtraxate as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
IfosfamideDrug
Patients will receive Ifsofamide as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
DexamethasoneDrug
Patients will receive dexamethasone as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
EtoposideDrug
Patients will receive etoposide as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
calaspargase pegolDrug
Patients will receive pegaspargase as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
cyclophosphamideDrug
Patients will receive cyclophosphamide as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
DoxorubicinDrug
Patients will receive doxorubicin as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
PrednisoneDrug
Patients will receive prednisone as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
Brentuximab VedotinDrug
Patients will receive brentuximab vedotin as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | 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. Receives: Drug: Methotrexate; Drug: Ifosfamide; Drug: Dexamethasone; Drug: Etoposide; Drug: calaspargase pegol |
| Cohort 2 | Experimental | 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. Receives: Drug: pralatraxate,; Drug: cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone; Drug: Brentuximab Vedotin |
What is being measured
The primary outcome is the main question the study is designed to answer.
overall response rate
to assess overall response rate following chemoimmunotherapy induction therapy
Measured: 1 year
Secondary outcomes (1)
event free survival
to determine the event free survival after induction chemoimmunotherapy and allogeneic stem cell transplantation
Measured: 2 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2018
- Study start1 Mar 2019
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NK-Cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Cohort 1 and 2 will be based on initial diagnosis.
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- New York Medical College
- Sponsor type
- University, hospital or other
- Collaborators
- University of Alabama at Birmingham
- Responsible party
- Principal investigator, Mitchell Cairo, New York Medical College
- Investigators
- Mitchell Cairo, MD, Study director, New York Medical College
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03719105
- Sponsor's protocol ID
- NYMC 575
- Status last verified
- Aug 2026
- First submitted
- 23 Oct 2018
- Last updated
- 18 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03719105
- Acronym / sponsor ID
- NYMC 575
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- New York Medical CollegeUniversity, hospital or other
- Collaborators
- University of Alabama at Birmingham
- Study start
- 1 Mar 2019 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 25 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Cohort 1 and 2 will be based on initial diagnosis.
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: Methotrexate, Drug: Ifosfamide, Drug: Dexamethasone, Drug: Etoposide, Drug: calaspargase pegolPatients 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. |
| Cohort 2 | Experimental | Drug: pralatraxate,, Drug: cyclophosphamide, Drug: Doxorubicin, Drug: Prednisone, Drug: Brentuximab VedotinPatients 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. |
Who may qualify
- Ages
- 1 year to 31 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (20 listed)
- Patients must weigh at least 10 kilograms at the time of the study enrollment.
- Diagnosis
- 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
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethotrexatePatients will receive methotrexate as part of chemoimmunotherapy regemin followed by allogeneic stem cell transplant. | Drug | Cohort 1 |
| pralatraxate,Patients will receive pralaxtraxate as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant. | Drug | Cohort 2 |
| IfosfamidePatients will receive Ifsofamide as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant. | Drug | Cohort 1 |
| DexamethasonePatients will receive dexamethasone as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant. | Drug | Cohort 1 |
| EtoposidePatients will receive etoposide as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant. | Drug | Cohort 1 |
| calaspargase pegolPatients will receive pegaspargase as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant. | Drug | Cohort 1 |
| cyclophosphamidePatients will receive cyclophosphamide as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant. | Drug | Cohort 2 |
| DoxorubicinPatients will receive doxorubicin as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant. | Drug | Cohort 2 |
| PrednisonePatients will receive prednisone as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant. | Drug | Cohort 2 |
| Brentuximab VedotinPatients will receive brentuximab vedotin as part of chemoimmunotherapy regimen followed by allogeneic stem cell transplant. | Drug | Cohort 2 |
Primary outcome
overall response rate
Time frame: 1 year
to assess overall response rate following chemoimmunotherapy induction therapy
1 secondary outcome
event free survival
Time frame: 2 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2026.
- Individual participant dataSharing planned: No
Related trials for NK-Cell Lymphoma
Active, not recruitingPhase 2
Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma
Adult T-Cell Leukemia/Lymphoma, Anaplastic Large Cell Lymphoma, ALK-Negative
Active, not recruitingObservational study
Multi-omics Profiling of Relapsed Extranodal Natural Killer (NK)/T-cell Lymphoma
Extranodal NK/T-cell Lymphoma, Nasal Type
Not yet recruitingPhase 1
BLinatumomab and iNKT in Relapsed B-Cell ALL
B-Cell ALL, ALL (Acute B-Lymphoblastic Leukemia)
Active, not recruitingPhase 1
A Study of Ruxolitinib and Duvelisib in People With Lymphoma
T-cell Lymphomas, NK-Cell Lymphomas
Not yet recruitingPhase 1
Study to Evaluate the Feasibility and Safety of Autologous Cytokine-Induced Killer Cells (CIK_D332) in Combination With Tafasitamab and Lenalidomide in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Diffuse Large B-Cell Lymphoma (DLBCL)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Mitchell Cairo, MD study director
New York Medical College
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Methotrexate, pralatraxate, and Ifosfamide in people with NK-Cell Lymphoma and NK-Cell Leukemia, run by New York Medical College at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ana Xavier ((205) 638-6763, axavier@peds.uab.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
overall response rate (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2026.