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

Overview

About this study

The purpose of this study 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.  It is a multicenter, multi-arm, international, phase Ib, 3 x 3 dose-escalation study with an initial phase I followed by an expansion phase.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

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 (Cheson et al., 2014).
  • Phase I: patient must have histologically confirmed relapsed or refractory Peripheral T-cell lymphoma (PTCL) or cutaneous T-cell Lymphoma (CTCL) with tumor stage as per WHO criteria andTNMB classification and staging. Expansion phase: patients must have histologically confirmed relapsed or refractory PTCL, relapsed or refractory CTCL with tumor stage mycosis fungoides (excluding de novo plaque and patches CTCL) as per WHO criteria andTNMB classification and staging, de novo PTCL, de novo tumor stage mycosis fungoides (excluding de novo plaque and patches 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.
  • 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 below; all screening labs should be performed within 10 days of treatment initiation.

Hematological

  • Absolute neutrophil count (ANC)
    • ≥ 1,000 /mcL
  • Platelets
    • ≥ 75,000 / mcL
  • Hemoglobin
    • ≥ 9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)

Renal

  • Serum creatinine OR Measured or calculated* creatinine clearance
    • GFR can also be used in place of creatinine or CrCl
    • ≤ 1.5 X upper limit of normal (ULN) OR ≥ 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
  • *Creatinine clearance should be calculated per institutional standard.

Hepatic

  • Serum total bilirubin
    • ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN
  • AST (SGOT) and ALT (SGPT)
    • ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
  • Albumin
    • >2.5 mg/dL

Coagulation

  • International Normalized Ratio (INR) or Prothrombin Time (PT)
    • ≤ 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Activated Partial Thromboplastin Time (aPTT)
    • ≤ 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • 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.
    • Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

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 confirmed diagnosis of de novo plaque and patches CTCL as per WHO criteria and does not require systemic treatment.
  • 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.
  • 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-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 within 30 days of planned start of study therapy.
    • 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

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Nabila Bennani, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

N. Nora Bennani, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

N. Nora Bennani, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20459374

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