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Phase I/II Study of Pembrolizumab in Patients Failing to Respond to or Relapsing After Anti-CD19 Chimeric Antigen Receptor Modified T Cell Therapy for Relapsed or Refractory CD19+ Lymphomas

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ClinicalTrials.gov Identifier: NCT02650999
Recruitment Status : Recruiting
First Posted : January 8, 2016
Last Update Posted : December 20, 2016
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
Single center, phase I/II trial of pembrolizumab after CTL019 for CD19+ lymphomas. Patients will have CD19+ diffuse large B-cell, follicular, or mantle cell lymphomas relapsed/refractory after CTL019. 12 total patients will be enrolled. Safety of pembrolizumab (primary endpoint) will be determined using a Bayesian monitoring rule for treatment-related adverse events causing drug discontinuation. Secondary efficacy endpoints include overall response rate and progression-free survival.

Condition or disease Intervention/treatment Phase
CD19+ Diffuse Large B-cell Lymphomas Follicular Lymphomas Mantle Cell Lymphomas Drug: Pembrolizumab Phase 1 Phase 2

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Study of Pembrolizumab in Patients Failing to Respond to or Relapsing After Anti-CD19 Chimeric Antigen Receptor Modified T Cell Therapy for Relapsed or Refractory CD19+ Lymphomas
Study Start Date : January 2016
Estimated Primary Completion Date : January 2019


Arms and Interventions

Arm Intervention/treatment
Experimental: Single Arm Drug: Pembrolizumab
200mg intravenously (IV)


Outcome Measures

Primary Outcome Measures :
  1. Number of adverse events [ Time Frame: 3 years ]

Eligibility Criteria

Information from the National Library of Medicine

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

Inclusion Criteria:

  • Histologically confirmed follicular lymphoma grade 1-3A, diffuse large B cell lymphoma, and mantle cell lymphoma by World Health Organization 2009 classification
  • Relapsed/refractory lymphoma after CTL019 - Be willing and able to provide written informed consent/assent for the trial.
  • Age 18 years or older on day of signing informed consent.
  • Have baseline imaging within 6 weeks of enrollment (CT, MR or PET/CT imaging) and have measurable disease on physical examination or imaging studies.

    -- Not pregnant or breastfeeding

  • Any lesion 1.5 cm in long axis dimension is considered measurable.
  • Performance status of 0-2 on the ECOG Performance Scale
  • Demonstrate adequate organ function.
  • Absolute neutrophil count (ANC) ≥1,000 /mcL
  • Platelets≥50,000 / mcL
  • Hemoglobin ≥8 g/dL without transfusion or EPO dependency (within 7 days of assessment)
  • Serum creatinine OR Measured or calculated a creatinine clearance (aCreatinine clearance should be estimated per institutional standard) (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
  • 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
  • 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.

Exclusion Criteria:

  1. 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. An exception will be made for patients who have received CTL019/CTL119 on experimental protocol; these patients will be eligible to enroll once progression of disease or failure to respond is documented by clinical or radiologic assessment.
  2. Patient has received intervening therapy for lymphoma after CTL019/CTL119 infusion.
  3. Has active cytokine release syndrome from CTL019/CTL119 infusion.
  4. Has a known history of active TB (Bacillus Tuberculosis).
  5. Hypersensitivity to pembrolizumab or any of its excipients.
  6. 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. Toxicities that are disease related will not exclude patients.
  7. 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 in the opinion of the Principal Investigator prior to starting therapy.
  8. 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.
  9. 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.
  10. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  11. Has known history of, or any evidence of active, non-infectious pneumonitis.
  12. Has an active infection requiring systemic therapy.
  13. 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.
  14. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  15. 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.
  16. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  17. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  18. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  19. 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.
  20. Has a history of (non-infectious pneumonitis that required steroids or has current pneumonitis.
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): NCT02650999


Contacts
Contact: Stephen Schuster, MD 855-216-0098 PennCancerTrials@emergingmed.com

Locations
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Stephen Schuster, MD    855-216-0098    PennCancerTrials@emergingmed.com   
Principal Investigator: Stephen Schuster, MD         
Sponsors and Collaborators
Abramson Cancer Center of the University of Pennsylvania
Investigators
Principal Investigator: Stephen Schuster, MD Abramson Cancer Center of the University of Pennsylvania
More Information

Responsible Party: Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier: NCT02650999     History of Changes
Other Study ID Numbers: UPCC 46415
First Posted: January 8, 2016    Key Record Dates
Last Update Posted: December 20, 2016
Last Verified: December 2016

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Pembrolizumab
Antineoplastic Agents