Clinical Trial 19149

Cancer Type: Malignant Hematology
Interventions:748645 (Ibrutinib); AMP-514 (Durvalumab); Bendamustine; CC-5013 (Lenalidomide); Durvalumab; Ibrutinib (Imbruvica); Lenalidomide (Revlimid); MEDI4736 (Durvalumab); PCI-32765 (Ibrutinib); Rituxan (rituximab); rituximab

Study Type: Treatment
Phase of Study: Phase I/II
Investigators:

  • Julio Chavez

Overview

Study Title

A Phase 1/2, Open Label, Multicenter Study To Assess The Safety And Tolerability Of Durvalumab (Anti-Pd-L1 Antibody) As Monotherapy And In Combination Therapy In Subjects With Lymphoma Or Chronic Lymphocytic Leukemia

Summary

The purpose of this study is to determine the recommended phase 2 dose, safety, efficacy, and pharmacokinetics/pharmacodynamics of durvalumab in participants with certain lymphoma subtypes or chronic lymphocytic leukemia (CLL).

Objective

Primary: Dose finding part (Phase 1): To assess the safety and tolerability of durvalumab when given in combination with lenalidomide and rituximab; ibrutinib; or bendamustine and rituximab to determine the recommended Phase 2 doses (RP2Ds) of each combination. Dose confirmation part (Phase 1): To assess the safety of durvalumab as monotherapy and when given in combination with lenalidomide and rituximab; ibrutinib; or bendamustine and rituximab at the RP2D. Dose expansion part (Phase 2): To evaluate the preliminary efficacy of durvalumab when given in combination with lenalidomide and rituximab; ibrutinib; or bendamustine and rituximab in subjects with lymphoma or CLL. Secondary: Dose finding and confirmation parts (Phase 1): To make a preliminary assessment of antitumor activity of durvalumab as monotherapy and when given in combination with lenalidomide and rituximab; ibrutinib; or bendamustine and rituximab in subjects with lymphoma or CLL. Dose expansion part (Phase 2): To assess the safety of durvalumab when given in combination with lenalidomide and rituximab;ibrutinib; or bendamustine and rituximab in subjects with lymphoma or CLL. All parts (Phase 1/2): To characterize the pharmacokinetics (PK) of durvalumab as monotherapy and when given in combination. To characterize the PK of lenalidomide and ibrutinib when given in combination with durvalumab. To determine the pharmacodynamic (Pd) effects of durvalumab as monotherapy. Exploratory: To explore population PK analyses including the influence of intrinsic and extrinsic factors that may influence durvalumab exposures. To determine the immunogenicity of durvalumab as monotherapy and when given in.combination. To explore PK/Pd relationship, explore pharmacodynamic mechanistic biomarkers for durvalumab and other combination agents in the study. To explore host immune and tumor molecular markers predictive of response to durvalumab and other agents when given in combination. To explore minimal residual disease (MRD) and its correlation with clinical outcome.

Inclusion Criteria

  • Potential participants who have histologically confirmed and documented B-cell lymphoma (e.g., follicular, diffuse large B-cell, mantle cell, small lymphocytic, or Hodgkin lymphoma) and chronic lymphocytic leukemia.
  • Have high-risk chronic lymphocytic leukemia/small lymphocytic lymphoma.
  • Was previously treated with at least one prior systemic chemotherapy, immunotherapy, or chemoimmunotherapy.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
  • Willing and able to undergo biopsy.
  • Has documented active relapsed or refractory disease requiring therapeutic intervention.
  • Potential participants with lymphoma who has measurable disease (≥ 2.0 cm in its longest dimension by computed tomography) or chronic lymphocytic leukemia in need of treatment.
  • Fulfill the laboratory requirements as per protocol.

  • Exclusion Criteria

  • Has central nervous system (CNS) or meningeal involvement by lymphoma.
  • Has any histopathologic finding consistent with myelodysplastic syndrome on bone marrow studies.
  • Has received any prior monoclonal antibodies against PD-1 or PD-L1 and/or any prior: Arm A only: ImiDs (e.g., lenalidomide, thalidomide); Arm B only: ibrutinib or other Bruton's tyrosine kinase (BTK) inhibitor; Arms C only: bendamustine.
  • Has active auto-immune disease.
  • A history of organ transplant or allogeneic hematopoietic stem cell transplantation.
  • Is seropositive for or active viral infection with hepatitis B virus (HBV) (hepatitis B surface antigen [HBsAg] positive and/or detectable viral DNA).
  • Has known seropositivity for or active infection for human immunodeficiency virus (HIV) or hepatitis C virus (HCV).
  • A history of primary immunodeficiency or tuberculosis.
  • Potential participant who has other invasive malignancy within 2 years (5 years for Arm A) except for noninvasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin, ductal carcinoma in situ of the breast, or incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) that has/have been surgically cured.