Clinical Trials /

A Safety and Tolerability Study of INCB053914 in Combination With INCB050465 in Diffuse Large B-Cell Lymphoma

NCT03688152

Description:

The purpose of this study is to evaluate the safety and tolerability of INCB053914 in combination with INCB050465 in relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

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

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Safety and Tolerability Study of INCB053914 in Combination With INCB050465 in Diffuse Large B-Cell Lymphoma
  • Official Title: A Phase 1b, Multicenter, Open-Label Study of the Safety and Tolerability of INCB053914 in Combination With INCB050465 in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: INCB 53914-102
  • NCT ID: NCT03688152

Conditions

  • Relapsed Diffuse Large B-Cell Lymphoma
  • Refractory Diffuse Large B-Cell Lymphoma

Interventions

DrugSynonymsArms
INCB053914INCB053914 + INCB050465
INCB050465INCB053914 + INCB050465

Purpose

The purpose of this study is to evaluate the safety and tolerability of INCB053914 in combination with INCB050465 in relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Trial Arms

NameTypeDescriptionInterventions
INCB053914 + INCB050465ExperimentalINCB053914 in combination with INCB050465.
  • INCB053914
  • INCB050465

Eligibility Criteria

        Inclusion Criteria:

          -  Relapsed or refractory DLBCL, which has been histologically documented, defined as
             having received at least 2 but no more than 5 prior systemic treatment regimens (eg,
             an anti-CD20 antibody, an anti-CD20 antibody with or without chemotherapy, or
             chemotherapy alone) and ineligible for further treatment with standard of care.

          -  Willing to undergo pretreatment and on-treatment incisional or excisional biopsy of
             nontarget adenopathy or extranodal lesions. Provision of the most recent, available
             archived tumor biopsy may satisfy the pretreatment biopsy.

          -  Measurable disease as defined by the Lugano classification criteria:

               -  ≥ 1 measurable nodal lesion (≥ 1.5 cm in longest dimension) or ≥ 1 measurable
                  extranodal lesion (> 1 cm in longest dimension) on CT scan or MRI

               -  ≥ 1 PET-avid lesion.

          -  Eastern Cooperative Oncology Group performance status 0 to 2.

          -  Willingness to avoid pregnancy or fathering children based on protocol-defined the
             criteria.

        Exclusion Criteria:

          -  Laboratory values outside the protocol-defined range at screening unless approved by
             the medical monitor.

          -  Primary mediastinal (thymic) large B-cell lymphoma or Richter's Syndrome.

          -  Known brain or central nervous system metastases or history of uncontrolled seizures.

          -  Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a
             limited field of radiation for palliation within 2 weeks of the first dose of study
             treatment.

          -  Allogeneic stem cell transplant within the last 6 months, or active graft-versus-host
             disease following allogeneic transplant, or autologous stem cell transplant within the
             last 3 months before the date of the first dose of study treatment.

          -  Use of immunosuppressive therapy following allogenic transplant within 28 days of the
             first dose of study treatment.

          -  Prior treatment with a PIM inhibitor, selective PI3Kδ inhibitor (eg, idelalisib), or a
             pan-PI3K inhibitor.

          -  Receipt of anticancer medications, therapies, or investigational drugs within
             protocol-defined intervals before the date of the first dose of study treatment.

          -  Current or previous other malignancy within 3 years of study entry, except cured (or
             treated with curative intent and no evidence of disease) basal or squamous cell skin
             cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in
             situ of the cervix, or other noninvasive or indolent malignancy without sponsor
             approval.

          -  History of liver function abnormality requiring investigation and/or treatment (eg,
             due to excessive alcohol or drug-induced liver injury).

          -  Significant concurrent, uncontrolled medical condition including, but not limited to,
             renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological,
             cerebral, or psychiatric disease.

          -  Chronic or current active infectious disease requiring systemic antibiotics,
             antifungal, or antiviral treatment, and exposure to a live vaccine within 30 days of
             study treatment administration.

          -  Known HIV infection.

          -  Evidence of HBV or HCV infection.

          -  History of stroke or intracranial hemorrhage within 6 months of the date of study
             treatment administration.

          -  History of clinically significant or uncontrolled cardiac disease.

          -  Presence of an abnormal ECG that is clinically meaningful. Screening QTc interval >
             480 milliseconds is excluded (corrected by Fridericia).

          -  Any condition that would, in the investigator's judgment, interfere with full
             participation in the study, including administration of study treatment and attending
             required study visits; pose a significant risk to the participant; or interfere with
             interpretation of study data.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of treatment-emergent adverse events (TEAEs)
Time Frame:Up to approximately 6 months
Safety Issue:
Description:TEAE is defined as an adverse event reported for the first time or worsening of a pre-existing event after the first dose of study treatment.

Secondary Outcome Measures

Measure:Cmax of INCB053914 in combination with INCB050465
Time Frame:Day 15
Safety Issue:
Description:Maximum observed plasma concentration.
Measure:Tmax of INCB053914 in combination with INCB050465
Time Frame:Day 15
Safety Issue:
Description:Time to maximum plasma concentration.
Measure:Cmin of INCB053914 in combination with INCB050465
Time Frame:Day 15
Safety Issue:
Description:Minimum observed plasma concentration during the dosing interval.
Measure:AUC0-t of INCB053914 in combination with INCB050465
Time Frame:Day 15
Safety Issue:
Description:Area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration.
Measure:Cl/F of INCB053914 in combination with INCB050465
Time Frame:Day 15
Safety Issue:
Description:Oral dose clearance.
Measure:Overall response rate
Time Frame:Up to approximately 6 months
Safety Issue:
Description:Defined as the percentage of participants with a complete remission (CR)/complete metabolic response (CMR) or partial remission (PR)/partial metabolic response (PMR) as defined by investigator assessment per revised Lugano classification criteria for lymphomas.
Measure:Duration of response
Time Frame:Up to approximately 6 months
Safety Issue:
Description:Defined as the time from first documented evidence of CR/CMR or PR/PMR until disease progression or death from any cause among participants who achieve an objective response, as determined by radiographic disease assessment.
Measure:Progression-free survival
Time Frame:Up to approximately 6 months
Safety Issue:
Description:Defined as the time from the date of the first dose of any study drug until the earliest date of disease progression, as determined by radiographic disease assessment, or death from any cause, whichever occurs first.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Incyte Corporation

Trial Keywords

  • Diffuse large B-cell lymphoma
  • DLBCL
  • Non-Hodgkin lymphoma
  • phosphatidylinositol 3-kinase delta inhibitor
  • PI3Kδ
  • PIM kinases

Last Updated

June 26, 2019