Avelumab in Relapsed and Refractory Peripheral T-cell Lymphoma

Phase 2

Completed

Conditions: T-Cell Lymphoma Relapsed
T-Cell Lymphoma Refractory

Interventions: Drug: Avelumab

Registration Number: NCT03046953

Lead Sponsor: University of Birmingham

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.

Detailed Description: The AVAIL-T trial is designed 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. 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 receive up to 8 cycles of avelumab treatment. Avelumab is an anti-PDL1 (programmed cell death receptor ligand 1) 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 avelumab, by measuring 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 & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 35

Inclusion Criteria

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.
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 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
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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Best Overall Response Rate During the First 8 Cycles of Treatment	8 cycles (224 days)	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.

Secondary Outcome Measures

Name	Time	Method
Duration of Response	2 years	Duration of response is defined as the time from first documented response (CR or PR) until relapse/progression, as determined by the Revised Response Criteria, or death. Patients who are relapse/progression free and alive at time of final analysis will be censored at date last seen.
Progression Free Survival	2 years	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.
Toxicity- Proportion of Patients	During treatment of 8 cycles (224 days)	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
Toxicity- Number of Patients	During treatment of 8 cycles (224 days)	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
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	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.
Overall Survival	Deaths were collected up to 2 years	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.