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Trial record 14 of 33 for:    pralatrexate

Study of Pembrolizumab Combined With Decitabine and Pralatrexate in PTCL and CTCL

This study is not yet open for participant recruitment.
Verified August 2017 by Owen A. O'Connor, Columbia University
Sponsor:
ClinicalTrials.gov Identifier:
NCT03240211
First Posted: August 7, 2017
Last Update Posted: August 28, 2017
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.
Collaborators:
University of Bologna
Samsung Medical Center
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Owen A. O'Connor, Columbia University
  Purpose
This is a multicenter, multi-arm, international, phase Ib, 3 x 3 dose-escalation study with an initial phase I followed by an expansion phase. The primary objective of the phase Ib is to determine the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), and dose limiting toxicity (DLT) of various combinations of pembrolizumab, pralatrexate and decitabine.

Condition Intervention Phase
PTCL CTCL Drug: Pembrolizumab Drug: Pralatrexate Drug: Decitabine Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This is a multicenter, international, phase Ib, 3 x 3 dose-escalation study with an initial phase I followed by an expansion phase.

There will be 3 treatment arms in this study.

Masking: None (Open Label)
Primary Purpose: Other
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 Pralatrexate

Resource links provided by NLM:


Further study details as provided by Owen A. O'Connor, Columbia University:

Primary Outcome Measures:
  • Estimated maximum Tolerated Dose (MTD) [ Time Frame: 1 year ]
    If 0 out of 3 patients will experience a DLT, 3 more patients will be enter at the next dose level. If 1 patient will experience a DLT, 3 more patients will be treated at the same dose level. If >1 patient will experience a DLT, then the dose escalation is stopped and this dose is declared MTD. The estimated MTD would be the highest dose at which 0/3 or 1/6 subjects experience a DLT, i.e. dose with an observed DLT rate of less than 0.33.

  • Recommended Phase 2 Dose [ Time Frame: 1 year ]
    Determine the recommended dose for the Phase 2 portion of the study based on the estimated MTD.


Other Outcome Measures:
  • Overall Response Rate (ORR) [ Time Frame: 1 year ]
    (ORR) (complete + partial response) will be evaluated using clinical parameters, computerized tomography (CT) scan (PET/CT scan is optional) and bone marrow biopsy, as outlined by the 2007 International Harmonization Project criteria and revised criteria (Lugano).

  • Progression free survival (PFS) [ Time Frame: 1 year ]
    The length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse.

  • Duration of response (DOR) [ Time Frame: 1 year ]
    The time between the initial response to therapy and subsequent disease progression or relapse.


Estimated Enrollment: 42
Anticipated Study Start Date: October 1, 2017
Estimated Study Completion Date: December 10, 2020
Estimated Primary Completion Date: September 10, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pembrolizumab plus Pralatrexate
Subjects will receive pembrolizumab 200 mg IV day 1 with pralatrexate 30 mg/m2 IV day 1, 8, and 15.
Drug: Pembrolizumab
Pembrolizumab 200 mg IV
Drug: Pralatrexate
Pralatrexate 20-30 mg/m2 IV
Experimental: Pembrolizumab plus Pralatrexate plus Decitabine
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.
Drug: Pembrolizumab
Pembrolizumab 200 mg IV
Drug: Pralatrexate
Pralatrexate 20-30 mg/m2 IV
Drug: Decitabine
Decitabine 10-20 mg/m2
Experimental: Pembrolizumab plus Decitabine
Subjects will receive pembrolizumab 200 mg IV and decitabine 20 mg/m2 from day 1 to 5.
Drug: Pembrolizumab
Pembrolizumab 200 mg IV
Drug: Decitabine
Decitabine 10-20 mg/m2

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 and escape from immune surveillance.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 90 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 based on the Lugano Criteria
  • Phase I: patient must have histologically confirmed relapsed or refractory Peripheral T-cell lymphoma (PTCL) or cutaneous T-cell Lymphoma (PTCL) as per World Health Organization (WHO) criteria. Expansion phase: patients must have histologically confirmed relapsed or refractory PTCL, relapsed or refractory CTCL, de novo PTCL, de novo tumor stage mycosis fungoides (excluding de novo plaque and patches CTCL) as per WHO criteria.
  • There is no upper limit for the number of prior therapies. Patient may have relapsed after prior autologous stem cell transplant.
  • Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Be willing to provide fine-needle aspiration (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 Eastern Cooperative Oncology Group (ECOG) Performance Scale.
  • Demonstrate adequate organ function, all screening labs should be performed within 10 days of treatment initiation.
  • Female subject 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 must be willing to use an adequate method of contraception - Contraception, for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  • Male subjects of childbearing potential must agree to use an adequate method of contraception - Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.

Exclusion Criteria:

  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  • Has a known history of active Bacillus Tuberculosis (TB)
  • Hypersensitivity to pralatrexate, or decitabine or pembrolizumab or any of its excipients.
  • Has received prior allogeneic stem cell transplant.
  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.

    • Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
    • Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • 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.
  • Has known history of, or any evidence of active, non-infectious pneumonitis.
  • 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-programmed death (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 (HCV) (e.g., HCV RNA [qualitative] is detected).
  • Has received a live vaccine within 30 days of planned start of study therapy.
  Contacts and Locations
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): NCT03240211


Contacts
Contact: Michelle Malanga 212-326-5731 mm4629@cumc.columbia.edu

Locations
United States, New York
51 West 51st Street, Suite 200 Not yet recruiting
New York, New York, United States, 10019
Contact: Michelle Malanga    212-326-5731    mm4629@cumc.columbia.edu   
Italy
University of Bologna Not yet recruiting
Bologna, Italy
Principal Investigator: Pier Luigi Zinzani, MD, PhD         
Korea, Republic of
Samsung Medical Center Not yet recruiting
Seoul, Korea, Republic of
Principal Investigator: Won Seog Kim, MD, PhD         
Sponsors and Collaborators
Owen A. O'Connor
University of Bologna
Samsung Medical Center
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Owen O'Connor, MD, PhD Columbia University
  More Information

Responsible Party: Owen A. O'Connor, Professor of Medicine, Columbia University
ClinicalTrials.gov Identifier: NCT03240211     History of Changes
Other Study ID Numbers: AAAR2435
First Submitted: July 31, 2017
First Posted: August 7, 2017
Last Update Posted: August 28, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Owen A. O'Connor, Columbia University:
Pembrolizumab
Decitabine
Pralatrexate
T-cell lymphoma

Additional relevant MeSH terms:
Lymphoma, T-Cell
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Pembrolizumab
Decitabine
Azacitidine
Aminopterin
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Folic Acid Antagonists