Study Of Durvalumab and Lenalidomide In R/R EBV Associated DLBCL Subtypes, Primary CNS And Testicular DLBCL

NCT03212807 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: SDBCC-LYM-16-02
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 4

Brief Summary

PHASE II STUDY OF DURVALUMAB IN COMBINATION WITH LENALIDOMIDE IN RELAPSED/REFRACTORY EBV ASSOCIATED SUBTYPES OF DLBCL, PRIMARY CNS LYMPHOMA AND PRIMARY TESTICULAR DLBCL Patients with relapsed refractory subtypes of DLBCL who fulfill the inclusion / exclusion criteria will be recruited to this trial and treated in this open label, phase 2 trial with the PDL1 inhibitor Durvalumab and Lenalidomide. The combination treatment will be given from the time of recruitment for 6 months when Lenalidomide will be stopped but Durvalumab will continue for a total of 2 years. Response will be assessed by PET / CT scans as per standard lugano criteria.

Conditions

EBV Related Non-Hodgkin's Lymphoma; Primary CNS Lymphoma; Primary Testicular Lymphoma

Keywords

Checkpoint inhibition; PDL1; EBV DLBCL; PCNSL

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Overall response rate (ORR) is defined as the proportion of patients with reduction in tumor burden of at least 50%. ORR will be reported with corresponding 95% confidence intervals using the exact binomial method.

  at least 6 months of follow up

Secondary Outcomes (2)

• Progression free survival

  12 months

• Overall Survival

  2 years

Study Arms (1)

Investigational

EXPERIMENTAL

Durvalumab + Lenalidomide

Drug: Durvalumab; Drug: Lenalidomide

Interventions

Durvalumab DRUG

Investigational Medicinal Product

Investigational

Lenalidomide DRUG

Investigational Medicinal Product

Investigational

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent for the trial.
• Be ≥ 21 years of age on the day of signing informed consent
• Histologically proven relapsed / refractory DLBCL classified under the following WHO Subtypes.
• i, EBV Positive DLBCL (of the elderly and immunosuppression associated) ii, T-cell / histiocyte-rich B-cell lymphoma iii, Plasmablastic lymphoma iv, Gray zone lymphoma v, Primary Mediastinal Large B-Cell Lymphoma vi, Primary CNS Lymphoma (DLBCL) vii, Primary testicular lymphoma The biopsy needs to have been obtained within 3 months of signing informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Patients must have received at least one course (1 - 6 cycles) of Immunochemotherapy for example Rituximab + Chemotherapy (CHOP or CHOP like) and must have relapsed or refractory disease at the time of trial entry.
• Patients should have been deemed ineligible or failed or refused an autologous stem cell transplant in situations where stem cell transplant is the accepted standard of care. In patients with chemo-refractory DLBCL, even if patient is suitable for ASCT, transplant is extremely unlikely to achieve a response and hence such patients can be recruited after careful consideration by the investigator in discussion with the treating physician.
• Have measureable disease, defined as at least one lesion that can be accurately measured in at least two dimensions on a CT scan or MRI scan in PCNSL. Minimum measurement must be \> 15 mm in the longest diameter by \>10 mm in the short axis.
• Minimum life expectancy of 3 months.
• Adequate hematological function (unless abnormalities are related to lymphoma infiltration of the bone marrow) within 30 days prior to signing informed consent, including:
• Absolute neutrophil count (ANC) ≥ 1.0 x 109/L
• Platelet count ≥ 50 x 109/L
• Hemoglobin ≥ 8 g/dL
• Adequate other organ functions as defined in protocol.
• Must be able to adhere to study visit schedules and other protocol requirements.

You may not qualify if:

• The presence of any of the following will exclude a patient from enrolment:
• Concomitant use of any other investigational agent or device
• Has active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxin, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years. (Subjects who have had a transplant greater than 5 years ago are eligible as long as there are no symptoms of GVHD).
• iv) Patients who have had Intrathecal chemotherapy within 2 weeks of trial entry if it was given at the time of diagnostic lumbar puncture could still be included.
• Known infection with human immunodeficiency virus (HIV).
• Patient has known clinically active hepatitis B; carriers of hepatitis B are permitted but need to be on appropriate anti-viral therapy or have regular hepatitis B DNA virus monitored as advised by a Gastroenterologist.
• Neuropathy \> Grade 2.
• Patients who are at a high risk of a thromboembolic event and are not willing to take venous thromboembolic prophylaxis.
• Myocardial infarction within 6 months prior to enrolment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant.
• Clinically significant active infection needing intravenous systemic therapy or uncontrolled intercurrent illness.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
• Has evidence of active, non-infectious pneumonitis
• Pregnant or lactating females.
• Coexistent second malignancy or history of prior malignancy within the preceding 3 years (excluding non-melanoma skin tumors or in situ carcinoma of the cervix).

Sponsors & Collaborators

• Singapore General Hospital: lead
• National Cancer Center Singapore, Singapore: collaborator
• National University Hospital, Singapore: collaborator
• Raffles Hospital, Singapore: collaborator

Study Sites (4)

National Cancer Center

Singapore, Singapore

Location

National University Hospital

Singapore, Singapore

Location

Raffles Hospital

Singapore, Singapore

Location

Singapore General Hospital

Singapore, Singapore

Location

MeSH Terms

Interventions

durvalumab; Lenalidomide

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Chandramouli Nagarajan, MD FRCPath

  Singapore General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2017
• First Posted: July 11, 2017
• Study Start: August 1, 2017
• Primary Completion: February 1, 2021
• Study Completion: August 1, 2023
• Last Updated: September 13, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share

Locations

SG (4)