Phase 2
Completed N=106
A Study to Determine Dose, Safety, and Efficacy of Durvalumab as Monotherapy and in Combination Therapy in Subjects With Lymphoma or Chronic Lymphocytic Leukemia
Source: ClinicalTrials.gov NCT02733042 ↗Enrolled (actual)
106
Serious AEs
58.5%
Results posted
Mar 2020
Primary outcomePrimary: Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) — 0; 3; 1; 0 Participants
Summary
This study is designed to determine the recommended phase 2 dose (RP2D), and the safety, and efficacy of durvalumab as monotherapy and when given in combination with lenalidomide and rituximab; ibrutinib; or bendamustine and rituximab at the RP2D in adults with lymphoma or chronic lymphocytic leukemia (CLL).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) |
0; 3; 1; 0; 0; 0 | — |
| PRIMARY Number of Participants With Treatment-emergent Adverse Events |
3; 3; 8; 3; 4; 3 | — |
| SECONDARY Overall Response Rate (ORR) During Durvalumab Treatment |
33.3; 66.7; 80.0; 66.7; 75.0; 33.3 | — |
| SECONDARY Overall Response Rate During the Entire Study |
66.7; 66.7; 80.0; 66.7; 75.0; 33.3 | — |
| SECONDARY Time to First Response |
70.85; 12.60; 18.20; 11.85; 13.40; 13.00 | — |
| SECONDARY Kaplan-Meier Estimate of Duration of Response |
10.14; NA; NA; NA; NA; 29.29 | — |
| SECONDARY Kaplan-Meier Estimate of Progression-free Survival (PFS) |
8.41; NA; NA; NA; 28.71; 9.69 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of Durvalumab |
420264.066; 361906.229; 331572.478; 392663.668 | — |
| SECONDARY Time to Maximum Plasma Concentration (Tmax) of Durvalumab |
0.0510; 0.0479; 0.0510; 0.0420 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Durvalumab |
3120149.759; 3225869.344; 2670168.397; 3053060.746 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Durvalumab |
4867431.378; 5818262.846; 4762968.345; 5593532.553 | — |
| SECONDARY Terminal Elimination Phase Half-Life (t½) of Durvalumab |
11.596; 17.344; 16.327; 15.399 | — |
| SECONDARY Clearance (CL) of Durvalumab |
0.3082; 0.2578; 0.3149; 0.2682 | — |
| SECONDARY Volume of Distribution (Vz) of Durvalumab |
5.155; 6.451; 7.418; 5.957 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of Lenalidomide |
141.881; 309.917; 107.635; 174.090 | — |
| SECONDARY Time to Maximum Observed Plasma Concentration (Tmax) of Lenalidomide |
1.9500; 1.1667; 3.0333; 1.000 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Lenalidomide |
789.297; 805.299 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of Ibrutinib |
129.704; 67.728; 86.840; 72.436 | — |
| SECONDARY Time to Maximum Observed Plasma Concentration (Tmax) of Ibrutinib |
2.000; 1.9333; 1.8833; 2.000 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Ibrutinib |
586.396; 436.855 | — |
| SECONDARY Change From Baseline in Soluble Programmed Cell Death Ligand-1 (sPD-L1) Concentration |
— | — |
Eligibility Criteria
Inclusion Criteria
- Subject who has histologically confirmed and documented B-cell lymphoma (eg, follicular, diffuse large B-cell, mantle cell, small lymphocytic, or Hodgkin lymphoma) and chronic lymphocytic leukemia.
- Subject who has high-risk chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).
- Subject who was previously treated with at least one prior systemic chemotherapy, immunotherapy, or chemoimmunotherapy.
- Subject who has the Eastern Cooperative Oncology Group performance status of 0, 1, or 2.
- Subject who is willing and able to undergo biopsy.
- Subject who has documented active relapsed or refractory disease requiring therapeutic intervention.
- Subject with lymphoma who has measurable disease (≥ 2.0 cm in its longest dimension by computed tomography) or chronic lymphocytic leukemia in need of treatment.
- Subject who fulfills the laboratory requirements as per protocol
Exclusion Criteria
- Subject who has central nervous system (CNS) or meningeal involvement by lymphoma.
- Subject who has any histopathologic finding consistent with myelodysplastic syndrome on bone marrow studies.
- Subject who received any prior monoclonal antibodies against programmed cell death-1 (PD-1) or programmed cell death ligand-1 (PD-L1) and/or any prior:
- Arm A only: drugs with immunomodulatory and other properties (eg, lenalidomide, thalidomide);
- Arm B only: ibrutinib or other Bruton's tyrosine kinase (BTK) inhibitor;
- Arms C only: bendamustine
- Subject who has active auto-immune disease.
- Subject who has history of organ transplant or allogeneic hematopoietic stem cell transplantation.
- Subject who is seropositive for or active viral infection with hepatitis B virus (HBV) (hepatitis B surface antigen [HBsAg] positive and/or detectable viral DNA)
- Subject who has known seropositivity for or active infection for human immunodeficiency virus (HIV) or hepatitis C virus (HCV).
- Subject who has history of primary immunodeficiency or tuberculosis.
- Subject who 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.
Data sourced from ClinicalTrials.gov (NCT02733042). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.