Avelumab in Relapsed and Refractory Peripheral T-cell Lymphoma

NCT03046953 | Completed Phase 2 Results

• 1 other identifier: RG_16-123
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

The AVAIL-T trial is a trial to find out how effective avelumab is at treating patients with primary T-cell lymphoma that is refractory to or has relapsed following initial treatment.

Conditions

T-Cell Lymphoma Relapsed; T-Cell Lymphoma Refractory

Keywords

Lymphoma

Outcome Measures

Primary Outcomes (1)

• Best Overall Response Rate During the First 8 Cycles of Treatment

  Best overall response rate (Completed response \[CR\] + partial remission \[PR\]) during the first 8 cycles of treatment will be assessed using contrast-enhanced CT scans of the neck, chest, abdomen and pelvis, using the Revised Response Criteria for Malignant Lymphoma. In this study CR = complete disappearance of all detectable clinical evidence of disease, so involved lymph nodes had regressed on CT scan to normal size. PR = al least a 50% decrease in size of the involved lymph nodes measured on CT scans.

  8 cycles (224 days)

Secondary Outcomes (6)

• Toxicity- Number of Patients

  During treatment of 8 cycles (224 days)

• Toxicity- Proportion of Patients

  During treatment of 8 cycles (224 days)

• Maximum Percentage Change in Sum of Product of Diameters

  During trial treatment of 8 cycles (224 days), comparing baseline with cycles 3, 6 and 8

• Duration of Response

  2 years

• Progression Free Survival

  2 years

Study Arms (1)

Avelumab

EXPERIMENTAL

Avelumab 10mg/kg by IV infusion once every 2 weeks. A maximum of 8 cycles, each cycle is 28 days.

Drug: Avelumab

Interventions

Avelumab DRUG

anti-PDL1 antibody

Also known as: MSB0010718C

Avelumab

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged ≥ 16 years
• Life expectancy \> 12 weeks
• ECOG (eastern oncology cooperative group) performance status ≤ 2
• Relapsed or refractory\* peripheral T-cell lymphoma including the following histologies: peripheral T-cell lymphoma not otherwise specified (PTCL NOS) , angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL), enteropathy associated T-cell lymphoma (EATL), extranodal NK (natural killer)/T- cell lymphoma (ENKL), transformed mycosis fungoides (LCT MF), hepatosplenic T-cell lymphoma (HSTCL) \* For all relapsed patients, relapse must be confirmed by tissue biopsy (or bone marrow trephine if no other tissue available). For refractory patients, a biopsy must have been obtained within the last 3 months
• Failed at least 1 prior therapy (but no upper limit of prior regimens)
• Adequate haematological function defined by at registration:
• absolute neutrophil count (ANC) ≥ 1.0 × 109/L, (unsupported)
• platelet count ≥ 75 × 109/L, (unsupported)
• haemoglobin ≥ 9 g/dL (may have been transfused)
• Adequate hepatic function defined by:
• total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range
• AST (aspartate aminotransferase) or ALT (alanine aminotransferase) levels ≤ 2.5 × ULN for all patients, or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver)
• Adequate renal function defined by an estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
• CT measurable disease with at least 1 lesion having short axis \> 1.5cm or splenomegaly \> 14cm in cranio-caudal length attributable to relapsed/non responding lymphoma
• Negative serum pregnancy test at screening for women of childbearing potential.

You may not qualify if:

• All patients with active central nervous system (CNS) involvement of lymphoma
• Prior organ transplantation, including allogeneic stem cell transplantation
• Significant acute or chronic infections including, among others:
• Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS),
• Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive)
• Current use of immunosuppressive medication, EXCEPT for the following:
• intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); Systemic corticosteroids at a maximum dose of ≤ 1 mg/kg of prednisone or equivalent during screening (to be stopped by day 1 of trial treatment); Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
• Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3)
• Persisting toxicity related to prior therapy of Grade \>1 NCI-CTCAE v 4.03; however, alopecia and sensory neuropathy Grade ≤ 2 or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable are acceptable
• Pregnancy or lactation
• Known alcohol or drug abuse
• Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to registration), myocardial infarction (\< 6 months prior to registration), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
• Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behaviour; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
• Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines

Sponsors & Collaborators

• University of Birmingham: lead
• Bloodwise: collaborator
• Pfizer: collaborator

Study Sites (1)

University College London Hospital

London, NW1 2BU, United Kingdom

Location

MeSH Terms

Conditions

Lymphoma

Interventions

avelumab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

For one of the secondary outcomes- the maximum percentage change in the sum of the products of diameters, calculated from measurements of target tumour masses assessed by CT scans- no reliable conclusions could be drawn from this analysis due to missing data and a lack of consistent reporting.

Results Point of Contact

• Title: C Morland Cinical Trial Coordinator
• Organization: CRCTU Birmingham

avail-t@trials.bham.ac.uk

+44 121 371 7862

Study Officials

• Simon Wagner, MD

  Univeristy of Leicester

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Model Details: Single Arm trial with bayesian design

Study Record Dates

• First Submitted: February 3, 2017
• First Posted: February 8, 2017
• Study Start: December 8, 2017
• Primary Completion: July 31, 2020
• Study Completion: July 27, 2021
• Last Updated: July 16, 2024
• Results First Posted: July 16, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)