Avelumab in Relapsed and Refractory Peripheral T-cell Lymphoma

T-Cell Lymphoma Relapsed Clinical Trial

— AVAIL-T  

Official title:

A Phase 2a Trial of Avelumab, an Anti-PDL1 Antibody, in Relapsed and Refractory Peripheral T-cell Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03046953
• Other study ID #: RG_16-123
• Status: Completed
• Phase: Phase 2
• Start date: November 14, 2017
• Est. completion date: July 27, 2021

Study information

• Verified date: October 2021
• Source: University of Birmingham
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 refratory to or has relapsed following initial treatment.

Description:

The AVAIL-T trial is designed to find out how effective avelumab is at treating patients with primary T-cell lymphoma that is refratory to or has relapsed following initial treatment. Up to 36 people will be taking part in the AVAIL-T trial at hospitals across the United Kingdom. All patients on the trial will be recruited over 2 years and recieve up to 8 cycles of avelumab treatment. Avelumab is an anti-PD-L1 antibody that will be given as an infusion once every 2 weeks in cycles lasting 28 days. The trial will be looking at the response to aveulumab, by mesuring the change in the tumour size using CT scans, and seeing how long that response is maintained. The trial will also look at toxicity, overall survival, and progression free survival.

In addition we will analyse blood samples and samples of the cancer to understand better how the cancer behaves. This may guide the investigators in developing better treatments in the future.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: July 27, 2021
• Est. primary completion date: July 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

• Male or female patients aged = 16 years

• Life expectancy > 12 weeks

• ECOG 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/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 or ALT 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.

• Highly effective contraception for both male and female patients if the risk of conception exists. (Note: women of childbearing potential and men able to father a child must agree to use 2 highly effective contraception, defined as methods with a failure rate of less than 1 % per year. Highly effective contraception is required from consent, throughout and for at least 60 days after avelumab treatment.

• Ability to give informed consent

Exclusion Criteria:

Patients are not eligible for the trial if they fulfill any of the following exclusion criteria:

• All patients with active 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 deteriorat e 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

• Active infection requiring systemic therapy

• Major surgery within 4 weeks of trial entry

• Patients and partners of childbearing potential not willing to use two methods of effective contraception during and for 60 days after therapy

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• T-Cell Lymphoma Refractory
• T-Cell Lymphoma Relapsed

Intervention

Drug:
• Avelumab
anti-PDL1 antibody

Locations

Country	Name	City	State
United Kingdom	University College London Hospital	London

Sponsors (3)

Lead Sponsor	Collaborator
University of Birmingham	Bloodwise, Pfizer

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Best overall resposne rate during the first 8 cycles of treatment	Best overall response rate (CR + 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	8 cycles (224 days)
Secondary	Toxicity- Number of Patients	Toxicity assessed using CTCAE v4.0 will be defined as the number of patients who experience one or more grade 3 or 4 adverse event or serious adverse event of any grade	During treatment of 8 cycles (224 days)
Secondary	Toxicity- Proportion of Patients	Toxicity assessed using CTCAE v4.0 will be defined as the proportion of patients who experience one or more grade 3 or 4 adverse event or serious adverse event of any grade	During treatment of 8 cycles (224 days)
Secondary	Maximum percentage change in sum of product of diameters	Maximum percentage change in the sum of the product of diameters (SPD) of target tumour masses assessed by contrast-enhanced CT scans of the neck, chest, abdomen and pelvis, using the Revised Response Criteria for Malignant Lymphoma	During trial treatment of 8 cycles (224 days)
Secondary	Duration of Response	Duration of response is defined as the time from first documented response until relapse/progression, as determined by the Revised Response Criteria, or death. Patients who are relapse/progression free and alive will be censored at date last seen.	2 years
Secondary	Progression free survival	Progression free survival is defined as the time from date of registration to the date of disease progression or date of death from any cause. Patients not reaching progression or death at the time of analysis will be censored at the last date they were known to be alive and progression free.	2 years
Secondary	Overall survival	Overall survival time is defined as the time from date of registration to the date of death from any cause. Patients discontinuing the study, lost to follow-up or still alive at the end of the study will be censored at the date of last follow-up.	2 years