Clinical Trials /

Umbralisib and Pembrolizumab in Treating Patients With Relapsed or Refractory Classical Hodgkin Lymphoma

NCT03776864

Description:

This phase II trial studies how well umbralisib and pembrolizumab work in treating patients with classical Hodgkin lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Umbralisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Giving umbralisib and pembrolizumab may work better in treating classical Hodgkin lymphoma.

Related Conditions:
  • Classical Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Umbralisib and Pembrolizumab in Treating Patients With Relapsed or Refractory Classical Hodgkin Lymphoma
  • Official Title: A Phase II Trial of Umbralisib and Pembrolizumab in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: RG1003718
  • SECONDARY ID: NCI-2018-02836
  • SECONDARY ID: 10075
  • NCT ID: NCT03776864

Conditions

  • Hodgkin's Lymphoma

Interventions

DrugSynonymsArms
PembrolizumabImmunoglobulin G4, Anti-(Human Programmed Cell Death 1), Lambrolizumab, MK-3475, SCH 900475Treatment (pembrolizumab, umbralisib)
UmbralisibTGR-1202, RP5264Treatment (pembrolizumab, umbralisib)

Purpose

This phase II trial studies how well umbralisib and pembrolizumab work in treating patients with classical Hodgkin lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Umbralisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Giving umbralisib and pembrolizumab may work better in treating classical Hodgkin lymphoma.

Detailed Description

      Patients receive pembrolizumab IV on day 1. Treatment repeats every 21 for up to 16 cycles in
      the absence of disease progression or unacceptable toxicity. Patients also receive umbralisib
      orally (PO) daily on days 1-21 days in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed up at 28 days, then up to 1 year.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pembrolizumab, umbralisib)ExperimentalPatients receive pembrolizumab IV on day 1. Treatment repeats every 21 for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive umbralisib PO daily on days 1-21 days in the absence of disease progression or unacceptable toxicity.
  • Pembrolizumab
  • Umbralisib

Eligibility Criteria

        Inclusion Criteria:

          -  Relapsed or refractory CHL that has received at least 3 prior lines of therapy

          -  Measurable fludeoxyglucose F-18 (FDG)-avid disease defined by standard criteria
             (Lugano 2014) and a minimum of 1.0 cm in diameter

          -  Prior treatment with anti-PD1 or anti-PDL1 therapy is allowed.

               -  Patients who are currently on anti-PD1 or anti-PDL1 therapy who have failed to
                  achieve a CR after at least 18 weeks of treatment may enroll on study. For these
                  patients, anti-PD1 or anti-PDL1 therapy may be delayed for screening and to align
                  pembrolizumab dosing with the expected cycle 1 day 1

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2

          -  Ability to swallow and retain oral medication

          -  Willingness and ability to comply with study and follow-up procedures, and give
             written informed consent

          -  Female subjects of childbearing potential must be surgically sterile, be
             post-menopausal (for at least 1 year prior to screening visit), or must have a
             negative pregnancy test within 3 days prior to cycle 1 day 1 and agree to use
             medically acceptable contraception throughout the study period and for 4 months after
             the last dose of either study drug. Men of reproductive potential may not participate
             unless they agree to use medically acceptable contraception throughout the study
             period and for 4 months after the last dose of either study drug

          -  Patients must be expected to receive at least 2 cycles of therapy

          -  Patients should have a life expectancy if untreated of >= 90 days in the opinion of
             the investigator

          -  Patients must have a FDG-positron emission tomography (PET)-computed tomography (CT)
             of chest, abdomen, and pelvis within 42 days of enrollment

          -  Absolute neutrophil count (ANC) > 750

          -  Platelet count > 40,000

          -  Total bilirubin =< 1.5 times the upper limit of normal (ULN)

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (if
             known liver involvement then =< 5 x ULN is allowed)

          -  Calculated creatinine clearance > 30 mL/min (as calculated by the Cockcroft-Gault
             formula)

        Exclusion Criteria:

          -  Patients receiving cancer therapy (i.e., chemotherapy, immunotherapy, biologic
             therapy, hormonal therapy, surgery and/or tumor embolization, prednisone > 10 mg or
             equivalent) or any investigational drug within 21 days of cycle 1 day 1. Patients
             receiving radiation therapy within 14 days from cycle 1 day 1. Anti-PD1 or anti-PDL1
             therapy in patients with less than a CR after 18 weeks of such therapy is permitted to
             continue on schedule

          -  Discontinuation from prior anti-PD1 or anti-PDL1 therapy due to immune-related adverse
             event or any other treatment-related adverse event

          -  Autologous transplantation within 100 days

          -  Prior allogeneic transplant within 12 months of initiation on study

          -  Active graft versus host disease (GVHD) within 90 days prior to cycle 1 day 1

          -  Evidence of active central nervous system lymphoma

          -  Pregnant or nursing women

          -  Evidence of chronic active hepatitis B or chronic active hepatitis C infection
             (hepatitis C virus [HCV]), active cytomegalovirus (CMV), or known history of human
             immunodeficiency virus (HIV). If hepatitis B core (HBc) antibody, HCV antibody or CMV
             immunoglobulin (Ig)M is positive, the patient should be evaluated for the presence of
             HBV, HCV or CMV by deoxyribonucleic acid (DNA) (polymerase chain reaction [PCR]) to
             determine presence or absence of active infection

          -  Prior exposure to idelalisib (CAL-101), duvelisib (IPI-145), or any drug that
             specifically inhibits phosphoinositide-3-kinase (PI3K)

          -  Evidence of ongoing active systemic bacterial, fungal or viral infection

          -  Any severe and/or uncontrolled medical conditions or other conditions that could
             affect their participation in the study such as:

               -  Symptomatic, or history of documented congestive heart failure (New York [NY]
                  Heart Association functional classification III-IV)

               -  Significant cardiovascular disease such as uncontrolled or symptomatic
                  arrhythmias, congestive heart failure, or myocardial infarction within 6 months
                  of randomization

               -  Concomitant use of medication known to cause QT prolongation or torsades de
                  pointes. Poorly controlled or clinically significant atherosclerotic vascular
                  disease including cerebrovascular accident (CVA), transient ischemic attack
                  (TIA), angioplasty, cardiac/vascular stenting within 3 months of randomization

          -  Patients with other prior malignancies except for adequately treated basal cell
             carcinoma, squamous cell carcinoma of the skin, breast or cervical cancer in situ, or
             other cancer from which the patient has been disease-free for 5 years or greater,
             unless approved by the protocol principal investigator

          -  Patients with an active autoimmune disorder (with the exception of autoimmune
             hemolytic anemia, idiopathic thrombocytopenic purpura [ITP] or vitiligo)

          -  History of non-infectious pneumonitis related to prior line of therapy
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete response rate
Time Frame:Up to 1 year
Safety Issue:
Description:Proportion of subjects with relapsed/ refractory classical Hodgkin Lymphoma (CHL) who achieve a complete response (CR) with a regimen of umbralisib (oral, daily) and pembrolizumab (IV, day 1 of 21-day cycles).

Secondary Outcome Measures

Measure:Overall response rate
Time Frame:Up to 1 year
Safety Issue:
Description:Proportion of subjects with relapsed/ refractory classical Hodgkin Lymphoma (CHL) who achieve an overall response (OR) with a regimen of umbralisib (oral, daily) and pembrolizumab (IV, day 1 of 21-day cycles).
Measure:Incidence of adverse events
Time Frame:Up to 28 days post-treatment
Safety Issue:
Description:Measured via CTCAE v4.0

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Washington

Last Updated

October 2, 2019