T-Cell Lymphoma Refractory, T-Cell Lymphoma Relapsed
Conditions
Keywords
Lymphoma
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.
Interventions
DRUGAvelumab
anti-PDL1 antibody
Sponsors
Bloodwise
Pfizer
University of Birmingham
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single Arm trial with bayesian design
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
| 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 |
| 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. |
| 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. |
| 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. |
Countries
United Kingdom
Participant flow
Recruitment details
Patient were recruited from November 14, 2017 to November 18, 2019 at 14 UK (United Kingdom) hospitals by clinician referral. The first patient was recruited on December 8, 2017, and the final patient recruited on November 18, 2019.
Pre-assignment details
Of 35 enrolled patients, only 32 started treatment. Of the 3 patients who did not start treatment, one died, one relapsed and one was found to be ineligible post registration.
Participants by arm
| Arm | Count |
|---|---|
| Avelumab Patients received Avelumab 10mg/kg by IV infusion once every 2 weeks. A maximum of 8 cycles, each cycle is 28 days.
Avelumab: anti-PDL1 antibody | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
| Overall Study | Relapse/progressive disease | 21 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Avelumab | — |
|---|---|---|
| Age, Continuous | 62.1 years STANDARD_DEVIATION 11.7 | — |
| BMI | 27.0 kg/m2 STANDARD_DEVIATION 5.1 | — |
| Diastolic blood pressure | 74.2 mmHg STANDARD_DEVIATION 9.8 | — |
| ECOG performance 0 | 17 Participants | — |
| ECOG performance 1 | 13 Participants | — |
| ECOG performance 2 | 4 Participants | — |
| ECOG performance Missing Data | 1 Participants | — |
| Height | 1.7 metres STANDARD_DEVIATION 0.1 | — |
| Histology Anaplastic large cell lymphoma | 1 Participants | — |
| Histology Angioimmunoblastic T-cell lymphoma | 11 Participants | — |
| Histology Extranodal NK/T-cell lymphoma | 4 Participants | — |
| Histology Missing data | 1 Participants | — |
| Histology Peripheral T-cell lymphoma not otherwise specified | 17 Participants | — |
| Histology Transformed mycosis fungoides | 1 Participants | — |
| Prior therapies | 3.0 years | — |
| Pulse | 83.7 bpm STANDARD_DEVIATION 21.7 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 6 Participants | — |
| Sex: Female, Male Male | 29 Participants | — |
| Systolic blood pressure | 127.0 mmHg STANDARD_DEVIATION 19.7 | — |
| Weight | 81.7 kg STANDARD_DEVIATION 17.3 | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 24 / 32 |
| other Total, other adverse events | 31 / 32 |
| serious Total, serious adverse events | 18 / 32 |
Outcome results
Primary
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.
Time frame: 8 cycles (224 days)
Population: The per-protocol population was used ,defined as all patients recruited to the trial who started treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Avelumab | Best Overall Response Rate During the First 8 Cycles of Treatment | 5 Participants |
Secondary
Duration of Response
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.
Time frame: 2 years
Population: Patients who responded
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Avelumab | Duration of Response | 13.3 months |
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.
Time frame: During trial treatment of 8 cycles (224 days), comparing baseline with cycles 3, 6 and 8
Population: 13 of the 32 patients who started treatment had available CT scans containing the target lesions at cycles 3, 6 or 8 for comparison with baseline, and these patients were included in this analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Avelumab | Maximum Percentage Change in Sum of Product of Diameters | -4.3 percentage change |
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.
Time frame: Deaths were collected up to 2 years
Population: Per-protocol population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Avelumab | Overall Survival | 10.41 months |
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.
Time frame: 2 years
Population: Per-protocol population defined as all patients recruited to the trial who started treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Avelumab | Progression Free Survival | 2.86 months |
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
Time frame: During treatment of 8 cycles (224 days)
Population: The number of patients in the per-protocol population who experience one or more grade 3 or 4 adverse event or serious adverse event of any grade
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Avelumab | Toxicity- Number of Patients | 21 Participants |
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
Time frame: During treatment of 8 cycles (224 days)
Population: The proportion of patients in the per-protocol population who experience one or more grade 3 or 4 adverse event or serious adverse event of any grade
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Avelumab | Toxicity- Proportion of Patients | 0.656 proportion of patients |