Clinical Trials Register

Summary
EudraCT Number:	2016-004879-46
Sponsor's Protocol Code Number:	RG_16-123
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2018-05-08
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2016-004879-46

A.3

Full title of the trial

AVAIL-T: A Phase 2a trial of Avelumab, an anti-PDL1 antibody, in relapsed and refractory peripheral T-cell lymphoma (PTCL)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Avelumab treatment for patients with relapsed/refractory T-cell Lymphoma

A.3.2

Name or abbreviated title of the trial where available

AVAIL-T - Avelumab in relapsed/refractory T-cell Lymphoma

A.4.1

Sponsor's protocol code number

RG_16-123

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03046953

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1192-4931

A.5.4

Other Identifiers

Name:	Sponsors number	Number:	RG_16-123
Name:	CAS code	Number:	NH2004

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	University of Birmingham
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Bloodwise
B.4.2	Country	United Kingdom
B.4.1	Name of organisation providing support	Pfizer
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University of Birmingham
B.5.2	Functional name of contact point	Avail-T Trial Coordinator
B.5.3	Address:
B.5.3.1	Street Address	Haematology Team, CRCTU, School of Cancer and Genetic Sciences
B.5.3.2	Town/ city	Edgbaston, Birmingham
B.5.3.3	Post code	B15 2TT
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	01214147673
B.5.5	Fax number	01214146061
B.5.6	E-mail	avail-t@trials.bham.ac.uk

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/16/1798
D.3 Description of the IMP
D.3.1	Product name	Avelumab
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Avelumab
D.3.9.1	CAS number	1537032-82-8
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Relapsed and refractory T-cell lymphoma

E.1.1.1

Medical condition in easily understood language

A cancer of the blood cells that has returned following treatment.

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10001413
E.1.2	Term	Adult T-cell lymphoma/leukaemia
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To identify the best overall response (complete and partial remissions) of patients with relapsed/refractory Pimary T-Cell Lymphoma to avelumab treatment during 8 cycles of treatment.

E.2.2

Secondary objectives of the trial

To assess the side effects of the treatment, measure the reduction in tumour size using CT scans, assess the how long the patient benefits from the treatment, determine the progression free surival and overall surival of patients treatment with relapsed/refractory Pimary T-Cell Lymphoma when treated with avelumab.
The trial will also be looking at the characteristics of your lymphoma cells, including the presence of a protein called PD-L1 and if we can find any of Lymphoma DNA in your blood during treatment and follow-up.

E.2.3

Trial contains a sub-study

E.3

Principal 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 of registration

• Failed at least 1 prior therapy (but no upper limit of prior regimens)
• Adequate haematological function defined by at registration:
o absolute neutrophil count (ANC) ≥ 1.0 × 109/L, (unsupported)
o platelet count ≥ 75 × 10 9/L, (unsupported)
o haemoglobin ≥ 90 g/L (may have been transfused)
• Adequate hepatic function defined by the following at registration:
o total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range (patients with elevated bilirubin due to Gilbert’s syndrome are eligible)
o 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

E.4

Principal 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:
o Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS),
o 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:
o 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
• 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 (e.g. the flu vaccine)
• 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

E.5 End points

E.5.1

Primary end point(s)

Best overall response (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

E.5.1.1

Timepoint(s) of evaluation of this end point

During the first 8 cycles of treatment (16weeks).

E.5.2

Secondary end point(s)

• Toxicity assessed using CTCAE v4.0 will be defined as the number and proportion of patients who experience one or more grade 3 or 4 adverse event or serious adverse event of any grade
• Best overall response rate (Partial Remission (PR) + Complete Response (CR)) at any time 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
• 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 Lymphoma27
• Duration of response is defined as the time from first documented response until relapse/progression, as determined by the Revised Response Criteria27, or death. Patients who are relapse/progression free and alive will be censored at date last seen.
• 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. Patients will be followed up for a minimum of 12 months.
• 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. Patients will be followed up for a minimum of 12 months.

Exploratory Outcome measures
• PD-L1 expression defined as the percentage of PD-L1
• Cell free Lymphoma DNA levels as measured in the patients peripheral blood and correlated to their clinical disease status
• Multicolour peripheral blood immunophenotyping

E.5.2.1

Timepoint(s) of evaluation of this end point

• Toxicity - The number and proportion of patients who experience one or more grade 3 or 4 adverse event or serious adverse event of any grade will be reported over the duration of the trial treatment
• Time to event outcomes will be estimated using Kaplan Meier method. Point estimates will be presented at 6 and 12 months with 95% confidence intervals.
• Reduction in tumour size measured as maximum percentage change in the radiological sum of the product of the diameters from baseline

Exploratory Outcome measures
•PD-L1 expression in baseline tumour samples
•Cell free Lymphoma DNA levels reported at Baseline, cycle 2, cycle 4, cycle 6, cycle 8, month 12, month 16 and month 24
• Multicolour peripheral blood immunophenotyping at baseline

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of trial will be last patients visit. The Trials Office will notify the MHRA and main REC that the trial has ended and will provide them with a summary of the clinical trial report within 12 months of the end of trial.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1