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A Study of Durvalumab in Combination With R-CHOP or Lenalidomide Plus R-CHOP in Previously Untreated High-Risk Diffuse Large B-Cell Lymphoma

This study is currently recruiting participants.
Verified October 2017 by Celgene
Sponsor:
ClinicalTrials.gov Identifier:
NCT03003520
First Posted: December 28, 2016
Last Update Posted: October 3, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Celgene
  Purpose

This Phase 2, two-arm, open-label study is designed to evaluate the safety, clinical activity, predictive biomarkers and pharmacokinetics/ pharmacodynamics of durvalumab in combination with R-CHOP (Arm A) or R2-CHOP (Arm B), followed by durvalumab consolidation therapy in previously untreated subjects with high-risk DLBCL.

Patients with non-ABC subtype (determined by gene expression profiling) will be allocated to Arm A while patients with ABC (activated B-cell type) subtype will be allocated to Arm B. Approximately 120 patients may be enrolled and assigned into the appropriate treatment arms dependent upon their cell of origin status.

Induction treatment with R-CHOP (± Lenalidomide) will last for a total of up to 6 to 8 treatment cycles (21 days cycle), and the total time on study treatment, including durvalumab consolidation, will last up to 12 months.


Condition Intervention Phase
Lymphoma, Large B-Cell, Diffuse Drug: Durvalumab Drug: Rituximab Drug: Doxorubicin Drug: Vincristine Drug: Cyclophosphamide Drug: Prednisone Drug: Lenalidomide Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A PHASE 2, OPEN-LABEL, MULTICENTER STUDY TO EVALUATE THE SAFETY AND CLINICAL ACTIVITY OF DURVALUMAB IN COMBINATION WITH RITUXIMAB, CYCLOPHOSPHAMIDE, DOXORUBICIN, VINCRISTINE, PREDNISONE (R-CHOP) OR WITH LENALIDOMIDE PLUS R CHOP (R2 CHOP) IN SUBJECTS WITH PREVIOUSLY UNTREATED, HIGH RISK DIFFUSE LARGE B CELL LYMPHOMA

Resource links provided by NLM:


Further study details as provided by Celgene:

Primary Outcome Measures:
  • Progression Free Survival at 24 months [ Time Frame: Up to 24 months after last patient is enrolled ]
    Subjects who have not experienced disease progression or death within 24 months after start of study treatment


Secondary Outcome Measures:
  • Treatment-Emergent Adverse Events (AEs) [ Time Frame: Up to 15 months after last patient is enrolled ]
    Number of participants with adverse event

  • Clinical response to study treatment in biomarker-defined subpopulations [ Time Frame: Up to 24 months after last patient is enrolled ]
    Identification and development of biomarkers predictive of clinical response to study treatment


Estimated Enrollment: 120
Actual Study Start Date: February 28, 2017
Estimated Study Completion Date: July 1, 2024
Estimated Primary Completion Date: June 22, 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (non-ABC DLBCL): Durvalumab in combination with R-CHOP
Durvalumab 1125 mg intravenously (IV) on Day 1 of each 21-day cycle in combination with 6 to 8 cycles R-CHOP (IV rituximab, doxorubicin, vincristine, and cyclophosphamide on Day 1; daily oral/IV prednisone/prednisolone from Day 1 to 5) followed by durvalumab monotherapy for up to a total of 12 months after start of study treatment.
Drug: Durvalumab
Durvalumab
Drug: Rituximab
Rituximab
Drug: Doxorubicin
Doxorubicin
Drug: Vincristine
Vincristine
Drug: Cyclophosphamide
Cyclophosphamide
Drug: Prednisone
Prednisone
Experimental: Arm B (ABC DLBCL): Durvalumab in combination with R2-CHOP
Durvalumab 1125 mg IV on Day 1 of each 21-day cycle in combination with 6 to 8 cycles R2-CHOP (IV rituximab, doxorubicin, vincristine and cyclophosphamide on Day 1; daily oral/IV prednisone/prednisolone from Day 1 to 5; daily oral lenalidomide 15 mg from Day 1 to 14) from Cycle 2 until end of induction therapy (Cycle 6 or Cycle 8), or starting Cycle 1 if ABC subtype is identified prior to Cycle 1 Day 1 (C1D1) followed by durvalumab monotherapy for up to a total of 12 months after start of study treatment.
Drug: Durvalumab
Durvalumab
Drug: Rituximab
Rituximab
Drug: Doxorubicin
Doxorubicin
Drug: Vincristine
Vincristine
Drug: Cyclophosphamide
Cyclophosphamide
Drug: Prednisone
Prednisone
Drug: Lenalidomide
Lenalidomide

Detailed Description:

This research study is conducted in patients with previously untreated, high-risk Diffuse Large B-cell Lymphoma (DLBCL). Patients with high-risk DLBCL typically have insufficient therapeutic outcomes. Therefore, the addition of novel agents to the currently used induction therapy (R-CHOP backbone) is a rational approach to improve therapeutic outcomes in this disease setting.

Based on pre-clinical and clinical observations, it is hypothesized that durvalumab will have activity in DLBCL because the PD 1/PD L1 pathway is involved in the pathophysiology of DLBCL. In particular, the addition of durvalumab may significantly augment the anti-tumor activity of R-CHOP against high-risk DLBCL subtypes.

There are different subtypes of DLBCL which are distinguished by their Cell of Origin (ABC, GCB, unclassifiable). About a third of DLBCL is of the ABC subtype and as those patients have a worse outcome when treated with R-CHOP, lenalidomide plus R-CHOP (R2-CHOP) will be used for patients with the ABC subtype.

The safety of durvalumab has already been explored. However, as there is limited clinical experience with durvalumab in DLBCL, the study is divided into two stages:

  • A Safety Run-in Stage to evaluate the safety of the treatment combinations until at least 10 subjects are included in each of the two treatment arms for a total of 20 subjects
  • An Expansion Stage to analyze the clinical activity of the treatment combinations in up to 100 additional subjects
  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. CD20+Diffuse Large B-Cell Lymphoma.
  2. Ann Arbor stage 3 or 4 or stage 2 with bulky disease
  3. High or high-intermediate disease risk.
  4. No prior anti-lymphoma treatment.
  5. Subject is willing and able to undergo biopsy.
  6. Investigator considers R-CHOP immunochemotherapy appropriate.
  7. ECOG performance status of 0-2.
  8. Adequate hematology laboratory results (absolute neutrophil count ≥ 1.5 x 10^9/L, platelet count ≥ 75 x 10^9/L, hemoglobin ≥ 10.0 g/dL).
  9. Adequate biochemistry laboratory results (AST/SGOT and ALT/SGPT ≤ 3.0 x upper limit of normal; bilirubin ≤ 2.0 mg/dL; creatinine clearance of ≥ 40 mL/min).
  10. Bi-dimensionally measurable disease (> 2.0 cm).
  11. Subject is using effective contraception.

Exclusion Criteria:

  1. Diagnosis of lymphoma other than Diffuse Large B-Cell Lymphoma.
  2. Composite lymphoma or transformed lymphoma.
  3. Primary or secondary Central Nervous System involvement by lymphoma.
  4. Seropositive or active viral infection with hepatitis B virus, human immunodeficiency virus or hepatitis C virus.
  5. History of other malignancies, unless disease-free for ≥ 5 years.
  6. Left ventricular ejection fraction < 50%.
  7. Peripheral neuropathy ≥ Grade 2.
  8. Prior use of lenalidomide, or monoclonal antibodies against CTLA-4, PD-1, or PD-L1.
  9. High risk of developing thromboembolic events, who are unwilling to take venous thromboembolism prophylaxis.
  10. Active or prior documented autoimmune or inflammatory disorders within the past 3 years.
  11. Current or prior use of immunosuppressive medication within 28 days before start of treatment.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03003520


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

  Show 45 Study Locations
Sponsors and Collaborators
Celgene
Investigators
Study Director: Oliver Manzke, Medical Doctor Celgene Corporation
  More Information

Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT03003520     History of Changes
Other Study ID Numbers: MEDI4736-DLBCL-001
2015-005173-20 ( EudraCT Number )
First Submitted: December 22, 2016
First Posted: December 28, 2016
Last Update Posted: October 3, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Celgene:
Lymphoma
Diffuse-large B-Cell Lymphoma
Durvalumab
Anti-PD-L1 Antibody
MEDI4736
Immune Checkpoint
Rituximab
Cyclophosphamide
Doxorubicin
Vincristine
Prednisone/Prednisolone
Lenalidomide

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Thalidomide
Rituximab
Liposomal doxorubicin
Lenalidomide
Doxorubicin
Prednisone
Vincristine
Prednisolone
Methylprednisolone Hemisuccinate
Antibodies, Monoclonal
Prednisolone acetate
Methylprednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents