PTCLPhase 1NCT03240211
Study of Pembrolizumab Combined With Decitabine and Pralatrexate in PTCL and CTCL
A Phase 1 study testing Pembrolizumab, Pralatrexate and Decitabine in people with PTCL and CTCL, run by University of Virginia at 2 sites in United States.
Trial summary
This is an international, multicenter, multi-arm, phase Ib, model-based dose-escalation study. The primary objectives of the study in each arm is to determine the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), dose limiting toxicities (DLTs) and to evaluate the clinical efficacy at the MTD of various… Read more about this study
- Who is it for?
- Ages 18 to 90 years
- What is being tested?
- Pembrolizumab, Pralatrexate and Decitabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 2 sitesUnited States
- Study dates
- 2 Feb 2022to 25 May 2026
- Phase
- 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 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be willing and able to provide written informed consent/assent for the trial.
- Be ≥ 18 years of age on day of signing informed consent.
- Have measurable disease as defined by the Lugano Criteria for PTCL and by the Global Response Score for CTCL.
- Patient must have histologically confirmed relapsed or refractory Peripheral T-cell lymphoma (PTCL) or cutaneous T-cell Lymphoma (CTCL) as per WHO criteria and TNMB classification and staging.
- There is no upper limit for the number of prior therapies. Patient may have relapsed after prior autologous stem cell transplant.
- Patients who had prior treatment for their disease, as long as there is radiographic evidence of refractory or relapsed disease and the patient meets all other clinical and laboratory criteria for study treatment.
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- Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Be willing to provide FNA of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor.
- Have a performance status of 0 or 1 on the ECOG Performance Scale.
- Demonstrate adequate organ function as defined in the protocol, all screening labs should be performed within 10 days of treatment initiation.
- Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Female subjects of childbearing potential (Section 7.7.9.2) must be willing to use an adequate method of contraception as outlined in Section 7.9.2 - Contraception for the course of the study through 120 days after the last dose of study medication.
- Male subjects of childbearing potential (Section 7.9.2) must agree to use an adequate method of contraception as outlined in Section 7.9.2- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.
Who cannot join
- Has lack of resolution of adverse events (AE) due to previously administered antineoplastic therapy to grade 1 or less according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
- Had prior therapy with PD-1 inhibitors.
- Has a diagnosis of immunodeficiency or has been receiving any immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Use of steroid equivalent to prednisone 10 mg/day does not constitute an exclusion criterion.
- Has a known history of active TB (Bacillus Tuberculosis)
- Hypersensitivity to pralatrexate, or decitabine or pembrolizumab or any of its excipients.
- Has received prior allogeneic stem cell transplant.
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- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. The following are exceptions to this criterion: subjects with vitiligo or alopecia; subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement; subjects with psoriasis not requiring systemic treatment; patients with autoimmune phenomena secondary to active lymphoma.
- Has known history of, or any evidence of non-infectious pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Has received a live vaccine or live-attenuated vaccine within 30 days of planned start of study therapy. Administration of killed vaccines is allowed.
- Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Virginia
Charlottesville, Virginia, 22911
Allegheny Health Network
Pittsburgh, Pennsylvania, 15212-4722
About this study
Official title: Novel Immuno-epigenetic Based Platform for Patients With Peripheral T-cell Lymphoma (PTCL) and Cutaneous T-cell Lymphoma (CTCL): an International Phase Ib Study of Pembrolizumab Combined With Decitabine and/or Pralatrexate
This is an international, multicenter, multi-arm, phase Ib, model-based dose-escalation study. The primary objectives of the study in each arm is to determine the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), dose limiting toxicities (DLTs) and to evaluate the clinical efficacy at the MTD of various combinations of pembrolizumab, pralatrexate and decitabine.
Read the detailed description
The peripheral T-cell lymphomas (PTCLs) are rare subtypes of Non-Hodgkin lymphoma (NHL) with unique clinicopathologic features and very unfavorable prognosis. Recently it has been demonstrated that PTCLs are characterized by recurrent mutations in epigenetic operators (e.g. TET2, DNMT3A, and IDH2) and escape from immune surveillance.
The safety and toxicity of these combinations will be evaluated throughout the entire study. Dose allocation in Arms A and C will be based upon a continual reassessment method (CRM), and combination allocation in Arm B will be conducted using a DLT-adapted partial order continual reassessment method (POCRM) for dose-finding with combinations of agents.
Study Hypothesis: If pralatrexate and/or decitabine functions in an immunomodulatory fashion then priming and modulating the malignant cells and the microenvironment will enhance the antitumor activity of pembrolizumab in patients with PTCLs and CTCLs.
- Being tested
- Pembrolizumab, Pralatrexate, Decitabine
- Keywords
- Pembrolizumab, Decitabine, Pralatrexate, T-cell lymphoma
- Medical subject headings
- Lymphoma, T-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called Keytruda
Pembrolizumab 200 mg IV
PralatrexateDrug
Also called Folotyn
Pralatrexate 20 or 30 mg/m2 IV push
DecitabineDrug
Also called Dacogen
Decitabine 10 mg/m2
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Pembrolizumab plus Pralatrexate | Experimental | Subjects will receive pembrolizumab 200 mg IV day 1 with pralatrexate 30 mg/m2 IV day 1, 8, and 15. Receives: Drug: Pembrolizumab; Drug: Pralatrexate |
| Arm B: Pembrolizumab plus Pralatrexate plus Decitabine | Experimental | Subjects will receive pembrolizumab 200 mg IV day 8 with pralatrexate 20 mg/m2 IV day 1, 8, and 15 and decitabine 10 mg/m2 from day 1 to 5 ( or day 1 to 3, depending on dose level). Receives: Drug: Pembrolizumab; Drug: Pralatrexate; Drug: Decitabine |
| Arm C: Pembrolizumab plus Decitabine | Experimental | Subjects will receive pembrolizumab 200 mg IV and decitabine 20 mg/m2 from day 1 to 5 (or day 1 to 3, depending on dose level). Receives: Drug: Pembrolizumab; Drug: Decitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
The study dose level that is recommended after the maximum target sample size of 10 participants are accrued to each arm
Measured: 1-2 years
Dose Limiting Toxicity (DLT)
Only DLT's that occur prior to the initiation of cycle 2 will be used to determine dose escalation/de-escalation decisions. DLT criteria are defined as any non-hematologic toxicity greater and/or equal to grade 3 except for exceptions outlined in the protocol.
Measured: 1-2 years
Overall Response Rate (ORR)
Evaluate the efficacy, as determined by the ORR (complete + partial response) for each Arm
Measured: 1-2 years
Secondary outcomes (4)
Anti-tumor activity
Describe the anti-tumor activity of the combinations in each Arm.
Measured: 1-2 years
ORR, PFS, DOR
Evaluate the efficacy, as determined by the overall response rate (ORR), progression free survival (PFS), and duration of response (DOR) for each Arm.
Measured: 1-2 years
Pharmacodynamic markers
Evaluate pharmacodynamic markers of drug effect in paired tissue biopsies (pre- and post-treatment).
Measured: 1-2 years
Pharmacokinetic Profile
Establish pharmacokinetic profile for pembrolizumab when administered with pralatrexate (Arm A), with decitabine (Arm C) and when given as a combination (Arm B) during cycle 1 only.
Measured: 1-2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2017
- Study start2 Feb 2022
- Primary completion24 Jul 2025
- Study completion25 May 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PTCLStudies of the same condition, open and under way.
- More trials run by University of VirginiaThe sponsor's other registered studies.
- 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
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- This is a multicenter, multi-arm, phase Ib, model-based dose-escalation study. There will be 3 treatment arms in this study.
- Masking
- None (open label)
- Enrolment
- 37 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nathan L. Roberts, University of Virginia
- Investigators
- Owen O'Connor, MD, PhD, Study chair, University of VirginiaEnrica Marchi, MD, PhD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03240211
- Sponsor's protocol ID
- PTCL-002
- Status last verified
- Apr 2026
- First submitted
- 31 Jul 2017
- Last updated
- 7 Apr 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 7 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Immuno-epigenetic Based Platform for Patients With Peripheral T-cell Lymphoma (PTCL) and Cutaneous T-cell Lymphoma (CTCL): an International Phase Ib Study of Pembrolizumab Combined With Decitabine and/or Pralatrexate
- ClinicalTrials.gov ID
- NCT03240211
- Acronym / sponsor ID
- PTCL-002
- Keywords
- Pembrolizumab, Decitabine, Pralatrexate, T-cell lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 37 participants (estimated)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, Otsuka Pharmaceutical Development & Commercialization, Inc.
- Study start
- 2 Feb 2022 (actual)
- Primary completion
- 24 Jul 2025 (actual)
- Study completion
- 25 May 2026 (estimated)
- First posted
- 7 Aug 2017 (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.
This is an international, multicenter, multi-arm, phase Ib, model-based dose-escalation study. The primary objectives of the study in each arm is to determine the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), dose limiting toxicities (DLTs) and to evaluate the clinical efficacy at the MTD of various combinations of pembrolizumab, pralatrexate and decitabine.
Detailed description
The peripheral T-cell lymphomas (PTCLs) are rare subtypes of Non-Hodgkin lymphoma (NHL) with unique clinicopathologic features and very unfavorable prognosis. Recently it has been demonstrated that PTCLs are characterized by recurrent mutations in epigenetic operators (e.g. TET2, DNMT3A, and IDH2) and escape from immune surveillance.
The safety and toxicity of these combinations will be evaluated throughout the entire study. Dose allocation in Arms A and C will be based upon a continual reassessment method (CRM), and combination allocation in Arm B will be conducted using a DLT-adapted partial order continual reassessment method (POCRM) for dose-finding with combinations of agents.
Study Hypothesis: If pralatrexate and/or decitabine functions in an immunomodulatory fashion then priming and modulating the malignant cells and the microenvironment will enhance the antitumor activity of pembrolizumab in patients with PTCLs and CTCLs.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- This is a multicenter, multi-arm, phase Ib, model-based dose-escalation study. There will be 3 treatment arms in this study.
| Arm | Type | Receives |
|---|---|---|
| Arm A: Pembrolizumab plus Pralatrexate | Experimental | Drug: Pembrolizumab, Drug: PralatrexateSubjects will receive pembrolizumab 200 mg IV day 1 with pralatrexate 30 mg/m2 IV day 1, 8, and 15. |
| Arm B: Pembrolizumab plus Pralatrexate plus Decitabine | Experimental | Drug: Pembrolizumab, Drug: Pralatrexate, Drug: DecitabineSubjects will receive pembrolizumab 200 mg IV day 8 with pralatrexate 20 mg/m2 IV day 1, 8, and 15 and decitabine 10 mg/m2 from day 1 to 5 ( or day 1 to 3, depending on dose level). |
| Arm C: Pembrolizumab plus Decitabine | Experimental | Drug: Pembrolizumab, Drug: DecitabineSubjects will receive pembrolizumab 200 mg IV and decitabine 20 mg/m2 from day 1 to 5 (or day 1 to 3, depending on dose level). |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Be willing and able to provide written informed consent/assent for the trial.
- Be ≥ 18 years of age on day of signing informed consent.
- Have measurable disease as defined by the Lugano Criteria for PTCL and by the Global Response Score for CTCL.
- Patient must have histologically confirmed relapsed or refractory Peripheral T-cell lymphoma (PTCL) or cutaneous T-cell Lymphoma (CTCL) as per WHO criteria and TNMB classification and staging.
- There is no upper limit for the number of prior therapies. Patient may have relapsed after prior autologous stem cell transplant.
Key exclusion criteria (19 listed)
- Has lack of resolution of adverse events (AE) due to previously administered antineoplastic therapy to grade 1 or less according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
- Had prior therapy with PD-1 inhibitors.
- Has a diagnosis of immunodeficiency or has been receiving any immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Use of steroid equivalent to prednisone 10 mg/day does not constitute an exclusion criterion.
- Has a known history of active TB (Bacillus Tuberculosis)
- Hypersensitivity to pralatrexate, or decitabine or pembrolizumab or any of its excipients.
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 |
|---|---|---|
| PembrolizumabAlso: KeytrudaPembrolizumab 200 mg IV | Drug | Arm A: Pembrolizumab plus Pralatrexate, Arm B: Pembrolizumab plus Pralatrexate plus Decitabine, Arm C: Pembrolizumab plus Decitabine |
| PralatrexateAlso: FolotynPralatrexate 20 or 30 mg/m2 IV push | Drug | Arm A: Pembrolizumab plus Pralatrexate, Arm B: Pembrolizumab plus Pralatrexate plus Decitabine |
| DecitabineAlso: DacogenDecitabine 10 mg/m2 | Drug | Arm B: Pembrolizumab plus Pralatrexate plus Decitabine, Arm C: Pembrolizumab plus Decitabine |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: 1-2 years
The study dose level that is recommended after the maximum target sample size of 10 participants are accrued to each arm
Dose Limiting Toxicity (DLT)
Time frame: 1-2 years
Only DLT's that occur prior to the initiation of cycle 2 will be used to determine dose escalation/de-escalation decisions. DLT criteria are defined as any non-hematologic toxicity greater and/or equal to grade 3 except for exceptions outlined in the protocol.
Overall Response Rate (ORR)
Time frame: 1-2 years
Evaluate the efficacy, as determined by the ORR (complete + partial response) for each Arm
4 secondary outcomes
Anti-tumor activity
Time frame: 1-2 years
ORR, PFS, DOR
Time frame: 1-2 years
Pharmacodynamic markers
Time frame: 1-2 years
Pharmacokinetic Profile
Time frame: 1-2 years
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 7 Apr 2026.
- Individual participant dataSharing planned: No
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Active, not recruitingPhase 1
A Dose Escalation Study Evaluating CPI-818 in Relapsed/Refractory T-Cell Lymphoma
T-cell Lymphoma
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. This study is not recruiting at the moment.
Owen O'Connor, MD, PhD study chair
University of Virginia
Enrica Marchi, MD, PhD principal investigator
University of Virginia
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pembrolizumab, Pralatrexate and Decitabine in people with PTCL and CTCL, run by University of Virginia at 2 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 12 inclusion and 19 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: under way, not looking for participants, as of the sponsor's last update on 7 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) (time frame: 1-2 years). The study lists 3 primary outcomes in all. 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 7 Apr 2026.