Clinical Trials /

Pembrolizumab for Patients With PD-L1 Diffuse Large B Cell Lymphoma (DLBCL)

NCT03990961

Description:

A non randomized, unblinded, open label phase 2 study to investigate the efficacy of pembrolizumab in patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL) with PD-L1 genetic alterations

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Double-Hit Lymphoma
  • Transformed Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab for Patients With PD-L1 Diffuse Large B Cell Lymphoma (DLBCL)
  • Official Title: Phase II Study of Pembrolizumab for PD-L1 Gene-Altered, Relapsed/Refractory DLBCL

Clinical Trial IDs

  • ORG STUDY ID: IRB19-0076
  • NCT ID: NCT03990961

Conditions

  • Diffuse Large B Cell Lymphoma
  • Lymphoma

Interventions

DrugSynonymsArms
PembrolizumabKeytrudaPembrolizumab Treatment

Purpose

A non randomized, unblinded, open label phase 2 study to investigate the efficacy of pembrolizumab in patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL) with PD-L1 genetic alterations

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab TreatmentExperimental
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          1. Male/female participants who are at least 18 years of age on the day of signing
             informed consent with a histologically confirmed diagnosis of DLBCL will be enrolled
             in this study.

             Note: Patients with high-grade B cell lymphomas not otherwised specified and those
             with MYC and BCL2 translocations (double hit lymphoma) are eligible, as are patients
             with transformed indolent lymphoma, so long as PD-L1 gene alterations are present.

          2. A male participant must agree to use a contraception during the treatment period and
             for at least 120 days after the last dose of study treatment. Participants must
             refrain from donating sperm during this period.

          3. A female participant is eligible to participate if she is not pregnant, not
             breastfeeding, and at least one of the following conditions applies:

               1. Not a woman of childbearing potential (WOCBP)

               2. A WOCBP who agrees to follow the contraceptive guidance during the treatment
                  period and for at least 120 days after the last dose of study treatment.

             C.) patient must have negative pregnancy test within 72 hours of beginning treatment
             if WOCBP

          4. The participant (or legally acceptable representative if applicable) provides written
             informed consent for the trial.

          5. Have measurable disease, defined as at least one lesion that can be accurately
             measured in at least two dimensions by CT scan. Minimum measurement must be >15 mm in
             the longest diameter by >10 mm in the short axis. Lesions situated in a previously
             irradiated area are considered measurable if radiographic progression has been
             demonstrated in such lesions.

          6. Participants must have available archived biopsy material (ideally to be performed
             shortly before enrollment at the time of most recent relapse) for PD-L1 FISH and
             correlative studies.

          7. There is evidence of a PD-L1 gene alteration within lymphoma cells as assessed by
             FISH.

          8. Participants must have received ≥ 2 lines of prior systemic therapy, ≥ 1 line of prior
             systemic therapy (if ineligible for or refused autologous stem cell transplantation),
             or have received 1 line of prior therapy with primary-refractory disease or have
             relapsed within 12 months from the time of initial diagnosis.

             Note: patients having undergone prior CAR T cell therapy are eligible, as are patients
             having received a prior allogeneic transplantation, provided they do not meet any of
             the exclusionary GVHD criteria, and are at least 5 years removed from the date of
             their transplant.

          9. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

         10. Have adequate organ function within 10 days prior to the date of treatment allocation.
             Please see below for Adequate Organ Function Laboratory Values:

               -  Hematological

                    -  Absolute neutrophil count (ANC) less than or equal to 1,000/microliters

                    -  Platelets less than or equal to 50,000/microliters

                    -  Hemoglobin less than or equal to 8.0 grams per decilitre

               -  Renal

                    -  Creatinine OR measured or calculated clearance (GFR can also be used in
                       place of creatinine or CrCl) greater than or equal to 1.5XULN OR less than
                       or equal to 30mL/min for participant with creatinine levels less than 1.5 X
                       institutional ULN

               -  Hepatic

                    -  Total bilirubin greater than or equal to 1.5 X ULN or direct bilirubin
                       greater than or equal to ULN for participants with total bilirubin levels
                       less than 1.5 x ULN

                    -  AST (SGOT) and ALT (SGPT) greater than or equal to 2.5 x ULN (greater than
                       or equal to 5 x ULN for participants with liver metastases)

               -  Coagulation

                    -  International normalized ratio (INR) OR prothrombin time (PT) and Activated
                       partial thromboplastin time (aPTT) greater than or equal to 1.5 x ULN unless
                       participant is receiving anticoagulant therapy as long as PT or aPTT is
                       within therapeutic range of intended use of anticoagulants.

        Exclusion Criteria:

          1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to treatment
             allocation . If the urine test is positive or cannot be confirmed as negative, a serum
             pregnancy test will be required.

          2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with
             an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4,
             OX-40, CD137).

          3. Has received chemotherapy, monoclonal antibody therapy, or targeted small molecule
             therapy within 4 weeks prior to the first dose of study medication. Subjects must have
             recovered (≤ Grade 1) from adverse events related to a previously administered agent
             (patients with ≤ Grade 2 neuropathy are eligible). Subjects who have previously
             received CAR T cell therapy are eligible provided that relapse occurred > 90 days
             following the date of CAR T cell infusion.

             Note: If a participant received major surgery, he or she must have recovered
             adequately from complications from the intervention prior to starting study treatment.

          4. Has received prior radiotherapy within 1 week of start of study treatment.
             Participants must have recovered from all radiation-related toxicities, not require
             corticosteroids, and not have had radiation pneumonitis.

          5. Has a histologic diagnosis of primary mediastinal lymphoma or gray zone lymphoma.

          6. Has known active CNS lymphoma and/or lymphomatous meningitis. Participants with
             previously treated brain metastases may participate provided they are radiologically
             stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging
             (note that the repeat imaging should be performed during study screening), clinically
             stable and without requirement of steroid treatment for at least 14 days prior to
             first dose of study treatment.

          7. Has received a live vaccine within 30 days prior to the first dose of study drug.
             Examples of live vaccines include, but are not limited to, the following: measles,
             mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
             Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection
             are generally killed virus vaccines and are allowed; however, intranasal influenza
             vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.

          8. Is currently participating in or has participated in a study of an investigational
             agent or has used an investigational device within 4 weeks prior to the first dose of
             study treatment.

          9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
             immunosuppressive therapy within 7 days prior to the first dose of study drug. Short
             courses of corticosteroids will be allowed for palliation of symptoms related to
             lymphoma, but must be discontinued within 7 days prior to the first dose of study
             drug.

         10. Subjects having received prior allogeneic stem cell transplant, must be at least 5
             years removed from the date of their transplant. The also must have no history of
             severe (grade 3-4) acute GVHD, and/or current > grade 1 acute GHVD. Subjects must not
             have active chronic GVHD that requires active immune suppression or more than 10 mg of
             prednisone/day or equivalent.

         11. Has a history of a solid organ transplant.

         12. Has a known additional malignancy that is progressing or has required active treatment
             within the past 3 years.

             Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of
             the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that
             have undergone potentially curative therapy are not excluded

         13. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.

         14. 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 (eg., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment.

         15. Has a history of (non-infectious) pneumonitis that required steroids or has current
             pneumonitis.

         16. Has an active infection requiring systemic therapy.

         17. Has a known history of Human Immunodeficiency Virus (HIV) infection.

         18. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
             reactive) or known active Hepatitis C virus (defined as detection of HCV RNA)
             infection.

         19. Has a known history of active TB (Bacillus Tuberculosis).

         20. Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the study, interfere with the subject's
             participation for the full duration of the study, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator.

         21. Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

         22. Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the study, starting with the screening visit through 120 days
             after the last dose of trial treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate (ORR) to pembrolizumab treatment compared to historical controls.
Time Frame:2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Duration of response (DOR) to pembrolizumab treatment
Time Frame:2 years
Safety Issue:
Description:
Measure:Progression-free survival (PFS)
Time Frame:2 years
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:5 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Chicago

Last Updated