Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

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

Protocol: OSU-15229

Full Title

A Phase I/II, Open Label, Multicenter Study to Assess The Safety and Tolerability of Durvalumbab (ANTI-PD-L1 ANTIBODY) as Monotherapy and in Combination Therapy in Subjects with Lymphoma or Chronic Lymphocytic Leukemia

Purpose

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, 253 subjects may be enrolled into 4 treatment

arms, including durvalumab monotherapy; durvalumab in combination with lenalidomide±

rituximab; ibrutinib; or rituximab ± bendamustine. The study will have 3 parts: dose

finding, dose confirmation, and dose expansion. Subjects receiving monotherapy may receive

combination therapy or involved-field radiation to a single nodal site at time of

progressive disease.

Are you eligible?

Inclusion Criteria:

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 following laboratory requirements

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.

Exclusion Criteria:

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 following laboratory requirements

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.

Non-Hodgkin’s Lymphoma (B- & T-Cell) Lymphoma