Non Hodgkin Lymphoma Clinical Trial
A Study to Determine Dose, Safety, and Efficacy of Durvalumab as Monotherapy and in Combination Therapy in Subjects With Lymphoma or Chronic Lymphocytic Leukemia
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).
Full Description
The study was to consist of 3 parts: dose-finding, dose-confirmation, and dose-expansion. In this study, 4 treatment arms were to be investigated:
Arm A: durvalumab and lenalidomide ± rituximab
Arm B: durvalumab and ibrutinib
Arm C: durvalumab and rituximab ± bendamustine
Arm D: durvalumab (monotherapy)
The study was to start with 3 dose-finding cohorts (Arms A, B, and C) and 1 dose-confirmation cohort (Arm D) in parallel. All treatment arms were to be open for enrollment at study start except in the US, where Arm D was to enroll depending on the availability of treatment slots and following the completion of assessment of responses from the combination therapy arms. For Arms A and C, prior to enrolling participants to receive all 3 drugs, the doublet combinations were to be evaluated. Once the doublet combinations were deemed tolerable, the eventual triplet combinations were to be tested.
On 05 September 2017, the US FDA issued a Partial Clinical Hold on the study Arm A. Following this Partial Clinical Hold no more participants were enrolled into study Arm A. Participants already enrolled and treated in Arm A who were receiving clinical benefit, based on the discretion of the investigator, could continue study treatment after being reconsented. Arm B and C completed dose confirmation. The dose expansion part of the study was not opened.
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.
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There are 52 Locations for this study
Gilbert Arizona, 85234, United States
Scottsdale Arizona, 85258, United States
Aurora Colorado, 80045, United States
Gainesville Florida, 32610, United States
Tampa Florida, 33612, United States
Atlanta Georgia, 30322, United States
Chicago Illinois, 60611, United States
Rochester Minnesota, 55905, United States
Saint Louis Missouri, 63110, United States
Hackensack New Jersey, 07601, United States
New York New York, 10065, United States
Rochester New York, 14642, United States
Rochester New York, 14642, United States
Columbus Ohio, 43210, United States
Oklahoma City Oklahoma, 73104, United States
Philadelphia Pennsylvania, 19107, United States
Houston Texas, 77030, United States
Houston Texas, 77030, United States
Houston Texas, 77030, United States
Bobigny Cedex , 93009, France
Creteil , 94010, France
Dijon Cedex , 21079, France
Marseille Cedex 9 , 13273, France
Montpellier Cedex 5 , 34295, France
Nantes , 44093, France
Nantes , 44093, France
Pessac Cedex , 33604, France
Pierre-Benite CEDEX , 69495, France
Pierre-Benite CEDEX , 69495, France
Rennes , 35033, France
Rouen Cedex , 76038, France
Essen , 45122, Germany
Göttingen , 37099, Germany
Homburg-Saar , 66421, Germany
Köln , 50924, Germany
München , 81377, Germany
Bologna , 40138, Italy
Brescia , 25123, Italy
Brescia , 25123, Italy
Milano , 20144, Italy
Milano , 20162, Italy
Napoli, Campania , 80131, Italy
Napoli, Campania , 80131, Italy
Pavia , 27100, Italy
Rozzano (milano) , 20089, Italy
Chuo-ku Tokyo, 104-0, Japan
Chuo-ku , 104-0, Japan
Isehara City, Kanagawa , 259-1, Japan
Nagoya , 464-8, Japan
Amsterdam , 1081 , Netherlands
Groningen , 9713 , Netherlands
Leiden , 2333 , Netherlands
Rotterdam , 3015 , Netherlands
Rotterdam , 3015 , Netherlands
Plymouth Devon, PL6 8, United Kingdom
Nottingham Nottinghamshire, NG5 1, United Kingdom
Leeds , LS9 7, United Kingdom
London , WC1E , United Kingdom
Manchester , M20 4, United Kingdom
Manchester , M20 4, United Kingdom
Nottingham , Ng5 1, United Kingdom
Oxford , 0X3 7, United Kingdom
Oxford , 0X3 7, United Kingdom
Plymouth , PL6 8, United Kingdom
Southampton , SO16 , United Kingdom
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