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Trial record 1 of 1 for:    MEDI4736-NHL-001
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A Study to Determine Dose, Safety, and Efficacy of Durvalumab as Monotherapy and in Combination Therapy in Subjects With Lymphoma or Chronic Lymphocytic Leukemia (FUSION NHL 001)

This study is currently recruiting participants.
See Contacts and Locations
Verified December 2016 by Celgene Corporation
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT02733042
First received: April 5, 2016
Last updated: December 9, 2016
Last verified: December 2016
  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.

Condition Intervention Phase
Lymphoma Leukemia, Lymphocytic, Chronic, B-Cell Drug: Durvalumab Drug: Lenalidomide Drug: Rituximab Drug: Ibrutinib Drug: Bendamustine Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Adverse Events (AEs)- Phase [ Time Frame: Up to approximately 5 years ]
    Number of participants with adverse events

  • Dose Limiting Toxicity (DLT) - Phase 1 [ Time Frame: Up to approximately 1 month ]
    Number of participants with a DLT

  • Non-Tolerated Dose (NTD)- Phase 1 [ Time Frame: Up to approximately 1 month ]
    A dose will be considered to be a non-tolerated dose (NTD) if ≥ 2 of 3 or 6 evaluable subjects in a dose level experience a Dose Limiting Toxicity (DLT).

  • Maximum Tolerated Dose (MTD)- Phase 1 [ Time Frame: Up to approximately 1 month ]
    Is defined as the highest dose level below the NTD with 0 of 3 or 1 of 6 (ie, < 1/3 of subjects) evaluable subjects experiencing DLTs during the DLT evaluation period.

  • Overall Response Rate (ORR)- Phase 2 [ Time Frame: Up to approximately 1 year ]
    Number of subjects with best disease response of complete response (CR) or partial response (PR) during durvalumab treatment based on the International Working Group (IWG) Response Criteria for Malignant Lymphoma (the Lugano Classification) (Cheson, 2014) or the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Response Criteria (Hallek 2008; 2012; 2013)


Secondary Outcome Measures:
  • Overall Response Rate- Phase 1 [ Time Frame: Up to approximately 1 year ]
    Number of subjects with best disease response of CR or PR during durvalumab treatment based on the IWG Response Criteria for Malignant Lymphoma (the Lugano Classification) or the IWCLL Response Criteria

  • Adverse Events (AEs) - Phase 2 [ Time Frame: Up to approximately 5 years ]
    Number of participants with adverse events

  • Overall Response Rate-Phase1/2 [ Time Frame: Up to approximately 5 years ]
    Number of subjects with best disease response of CR or PR during study treatment based on the IWG Response Criteria for Malignant Lymphoma (the Lugano Classification) or the IWCLL Response Criteria

  • Duration of response (DoR)- Phase1/2 [ Time Frame: Up to approximately 5 years ]
    Time from first response (CR/PR) to progressive disease (PD) or death

  • Progression free survival (PFS) - Phase 1/2 [ Time Frame: Up to approximately 5 years ]
    Time from first study treatment dose to the first documented PD or death due to any cause, whichever occurs first time from first study treatment dose to the first documented PD or death due to any cause, whichever occurs first

  • Pharmacokinetics - AUC [ Time Frame: Up to approximately 2 months ]
    Area under the concentration-time curve

  • Pharmacokinetics - Tmax [ Time Frame: Up to approximately 2 months ]
    Time to maximum concentration

  • Pharmacokinetics - t1/2 [ Time Frame: Up to approximately 2 months ]
    Terminal half-life

  • Pharmacokinetics - CL/F [ Time Frame: Up to approximately 2 months ]
    Apparent total body clearance

  • Pharmacokinetics - Vz/F [ Time Frame: Up to approximately 2 months ]
    volume of distribution

  • Pharmacodynamics - Phase 1 [ Time Frame: Up to approximately 1 year ]
    Individual soluble PDL-1 levels [pg/mL] in blood with durvalumab monotherapy


Estimated Enrollment: 253
Study Start Date: May 2016
Estimated Study Completion Date: June 2024
Estimated Primary Completion Date: June 2024 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: Durvalumab plus Lenalidomide and Rituximab

Subjects assigned to Arm A will receive:

  • Durvalumab 1500 mg (IV) infusion on Day 1 of Cycles 1 through 13 (ie, 12 months) and
  • Lenalidomide (oral) at assigned dose levels (10 mg or 20 mg) once daily on Days 1 to 21 (inclusive) of:

    • Cycles 1 through 13 in indolent Non-Hodgkin lymphoma (NHL) (ie, FL or MZL) or
    • All cycles of treatment period until disease progression, unacceptable toxicity, or discontinuation for any other reason in aggressive NHL
  • Rituximab 375 mg/m2 (IV) infusion on Days 2, 8, 15 and 22 of Cycle 1 and on Day 1 from Cycles 2 through 5.

One cycle is 28-day.

Drug: Durvalumab
Other Name: MEDI4736
Drug: Lenalidomide Drug: Rituximab
Experimental: Arm B: Durvalumab Plus Ibrutinib

Subjects assigned to Arm B will receive:

  • Durvalumab (IV) infusion on Day 1 of Cycles 1 through 13
  • Ibrutinib (oral) at assigned dose levels (280 mg, 420 mg, or 560 mg)continuous once daily until disease progression, unacceptable toxicity or discontinuation for any other reason One cycle is 28-day.
Drug: Durvalumab
Other Name: MEDI4736
Drug: Ibrutinib
Experimental: Arm C: Durvalumab Plus Bendamustine and Rituximab

Subjects assigned to Arm C will receive:

  • Durvalumab 1500 mg (IV) infusion on Day 1 of Cycles 1 through 13
  • Bendamustine (IV) infusion at assigned dose levels (70 mg/m2 or 90 mg/m2) on Days 1 and 2 of Cycles 1 through 6
  • Rituximab 375 mg/m2 (IV) infusion on Day 2 Cycles 1 through 6 One cycle is 28-day.
Drug: Durvalumab
Other Name: MEDI4736
Drug: Rituximab Drug: Bendamustine
Experimental: Arm D: Durvalumab Monotherapy

Subjects assigned to Arm D will receive:

• Durvalumab (IV) infusion at a fixed dose of 1500 mg, on Day 1 of Cycles 1 through 13. One cycle is 28-day.

Drug: Durvalumab
Other Name: MEDI4736

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02733042

Contacts
Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com

  Show 48 Study Locations
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Myron S Czuczman Celgene
  More Information

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT02733042     History of Changes
Other Study ID Numbers: MEDI4736-NHL-001
Study First Received: April 5, 2016
Last Updated: December 9, 2016

Keywords provided by Celgene Corporation:
Lymphoma
Chronic Lymphocytic Leukemia
Durvalumab
Anti-PD-L1 Antibody
MEDI4736
Immune Checkpoint
Lymphatic Disease
B-Cell Malignancies
Abscopal Effect
Lenalidomide
Bendamustine
Rituximab
Ibrutinib
Lymphoma, B-Cell
Lymphoma, Non Hodgkin,
Hodgkin Disease
Leukemia, Lymphocytic, Chronic, B-Cell,
Lymphoma, Follicular
Lymphoma, Diffuse Large B-Cell
Lymphoma, Mantle Cell
Lymphoma, Small Lymphocytic
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders

Additional relevant MeSH terms:
Lymphoma
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Lenalidomide
Rituximab
Thalidomide
Bendamustine Hydrochloride
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on August 18, 2017