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Pembrolizumab in Patients Failing to Respond to or Relapsing After CAR T Cell Therapy for Relapsed or Refractory Lymphomas

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02650999
Recruitment Status : Active, not recruiting
First Posted : January 8, 2016
Results First Posted : May 12, 2020
Last Update Posted : May 12, 2020
Sponsor:
Information provided by (Responsible Party):
Abramson Cancer Center of the University of Pennsylvania

Tracking Information
First Submitted Date  ICMJE January 7, 2016
First Posted Date  ICMJE January 8, 2016
Results First Submitted Date  ICMJE April 28, 2020
Results First Posted Date  ICMJE May 12, 2020
Last Update Posted Date May 12, 2020
Study Start Date  ICMJE January 2016
Actual Primary Completion Date February 25, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 11, 2020)
Dose-limiting Toxicity [ Time Frame: 3 years ]
Percentage of subjects who discontinued therapy due to dose-limiting toxicity
Original Primary Outcome Measures  ICMJE
 (submitted: January 7, 2016)
Number of adverse events [ Time Frame: 3 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 11, 2020)
Overall Response Rates [ Time Frame: 3 months ]
3 months Overall response rates
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pembrolizumab in Patients Failing to Respond to or Relapsing After CAR T Cell Therapy for Relapsed or Refractory Lymphomas
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • CD19+ Diffuse Large B-cell Lymphomas
  • Follicular Lymphomas
  • Mantle Cell Lymphomas
Intervention  ICMJE Drug: Pembrolizumab
200mg intravenously (IV)
Study Arms  ICMJE Experimental: Pembrolizumab
Single arm, pembrolizumab 200mg IV every 3 weeks until progression/toxicity
Intervention: Drug: Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: January 7, 2016)
12
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2021
Actual Primary Completion Date February 25, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02650999
Other Study ID Numbers  ICMJE UPCC 46415
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Abramson Cancer Center of the University of Pennsylvania
Study Sponsor  ICMJE Abramson Cancer Center of the University of Pennsylvania
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Stephen Schuster, MD Abramson Cancer Center of the University of Pennsylvania
PRS Account Abramson Cancer Center of the University of Pennsylvania
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP