A Study to Determine Dose, Safety, and Efficacy of Durvalumab as Monotherapy and in Combination Therapy in Subjects With Lymphoma or Chronic Lymphocytic Leukemia

Status:	Active, not recruiting
Conditions:	Blood Cancer, Lymphoma
Therapuetic Areas:	Oncology
Healthy:	No
Age Range:	18 - Any
Updated:	10/19/2018
Start Date:	May 3, 2016
End Date:	July 8, 2022

A Phase 1/2, Open-label, Multi-center Study to Assess the Safety and Tolerability of Durvalumab (Anti-PDL1 Antibody) as Monotherapy and in Combination Therapy in Subjects With Lymphoma or Chronic Lymphocitic Leukemia

This open-label, multicenter, global study is designed to determine the recommended phase 2
dose, safety, efficacy, and pharmacokinetics/pharmacodynamics of durvalumab in subjects with
certain lymphoma subtypes or CLL. Globally, 265 subjects were to be enrolled into 4 treatment
arms, including durvalumab monotherapy; durvalumab in combination with lenalidomide±
rituximab; ibrutinib; or rituximab ± bendamustine. Originally the study had 3 parts: dose
finding, dose confirmation, and dose expansion. Subjects receiving monotherapy could receive
combination therapy or involved-field radiation to a single nodal site at time of documented
progressive disease. On 05-Sep-2017, the US FDA issued a Partial Clinical Hold on the study
Arm A. Following this Partial Clinical Hold no more subjects were enrolled into study Arm A.
Arm B and C completed dose confirmation. No dose expansion followed the completion of dose
confirmation for Arm B and C. Accrual was completed on Feb-2018 with 106 subjects enrolled
into the study.

Inclusion Criteria:

1. 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.

2. Subject who has high-risk chronic lymphocytic leukemia/small lymphocytic lymphoma.

3. Subject who was previously treated with at least one prior systemic chemotherapy,
immunotherapy, or chemoimmunotherapy.

4. Subject who has the Eastern Cooperative Oncology Group performance status of 0, 1, or
2.

5. Subject who is willing and able to undergo biopsy.

6. Subject who has documented active relapsed or refractory disease requiring therapeutic
intervention.

7. 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.

8. Subject who fulfills the laboratory requirements as per protocol

Exclusion Criteria

1. Subject who has central nervous system (CNS) or meningeal involvement by lymphoma.

2. Subject who has any histopathologic finding consistent with myelodysplastic syndrome
on bone marrow studies.

3. Subject who received any prior monoclonal antibodies against PD-1 or PD-L1 and/or any
prior:

1. Arm A only: ImiDs (eg, lenalidomide, thalidomide);

2. Arm B only: ibrutinib or other Bruton's tyrosine kinase (BTK) inhibitor;

3. Arms C only: bendamustine

4. Subject who has active auto-immune disease.

5. Subject who has history of organ transplant or allogeneic hematopoietic stem cell
transplantation.

6. 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)

7. Subject who has known seropositivity for or active infection for human
immunodeficiency virus (HIV) or hepatitis C virus (HCV).

8. Subject who has history of primary immunodeficiency or tuberculosis.

9. 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.

We found this trial at

sites

Shands Cancer Center / University of Florida

Gainesville, Florida 32610

from

Gainesville, FL