Follicular Lymphoma, Non Hodgkin Lymphoma, Relapsed Follicular Lymphoma
Conditions
Keywords
Radioimmunotherapy, Lu-177, Betalutin, Phase 1b, Combination, Rituximab
Brief summary
This study is a Phase 1b, open-label, single arm dose escalation study of Betalutin followed by rituximab in patients with previously treated follicular lymphoma. The purpose of this study is to characterise the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumour activity of Betalutin in combination with rituximab.
Interventions
10 MBq/kg Betalutin, lilotomab 40mg, rituximab 375 mg/m2
15 MBq/kg Betalutin, lilotomab 40mg, rituximab 375 mg/m2
Sponsors
ICON Clinical Research
Nordic Nanovector
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient must be ≥18 years at the time of signing the informed consent * ECOG performance status of 0-2 * Histologically confirmed diagnosis (by 2008 World Health Organization \[WHO\] classification) of follicular lymphoma (grade 1, 2 or 3a) * At least one (but not more than 3) prior regimens with an anti-CD20 antibody (alone or in combination with chemotherapy), with documented relapsed, refractory disease (must not be anti-CD20 antibody-refractory) or PD * Presence of at least one bi-dimensionally measurable lesion by CT or MRI: longest diameter (LDi) \>1.5 cm for a nodal lesion; LDi \>1.0 cm for an extranodal lesion within 28 days prior to start of treatment * Normal organ and bone marrow function defined as: 1. Absolute neutrophil count ≥1.5 x 109/L; 2. Platelet count ≥150 x 109/L; 3. Haemoglobin ≥9 g/dL; 4. Total bilirubin ≤1.5 x upper limit of normal (ULN) (except patients with documented Gilbert's syndrome \[\<3.0 mg/dL\]); 5. Aspartate transaminase (AST); Alanine transaminase (ALT) or Alkaline phosphatase (ALP) ≤2.5 x ULN (or ≤5.0 x ULN if liver involvement by primary disease); 6. Adequate renal function as demonstrated by a serum creatinine within the upper limit of normal range * Bone marrow involvement by lymphoma \<25% * Life expectancy \>3 months * Negative hepatitis B, hepatitis C and human immunodeficiency virus (HIV) screening tests * Patients must agree to use effective contraception for 12 months following last study drug administration
Exclusion criteria
* Previous haematopoietic stem cell transplantation (autologous and allogenic) * Evidence of histological transformation from FL to DLBCL at time of screening. * Previous total body irradiation * Chemotherapy, immunotherapy or investigational therapy within 28 days before the start of study drug administration (corticosteroid treatment at doses of ≤20 mg/day, topical or inhaled corticosteroids, granulocyte colony-stimulating factor \[G-CSF\] or granulocyte-macrophage colony-stimulating factor \[GM CSF\] are permitted up to 2 weeks prior to start of study treatment) or failure to recover from AEs associated with prior treatment * Previous treatment with radioimmunotherapy * Patients who are receiving any other investigational medicinal products * Known or suspected central nervous system (CNS) involvement of lymphoma * History of a previous treated cancer except for the following: 1. adequately treated local basal cell or squamous cell carcinoma of the skin 2. cervical carcinoma in situ 3. superficial bladder cancer or localised prostate cancer undergoing surveillance or surgery 4. localised breast cancer treated with surgery and radiotherapy but not including systemic chemotherapy 5. other adequately treated Stage 1 or 2 cancer currently in CR * Pregnant or lactating women * Exposure to another CD37 targeting drug * A known hypersensitivity to RTX, lilotomab, Betalutin or murine proteins or any excipient used in RTX, lilotomab or Betalutin * Receipt of live, attenuated vaccine within 30 days prior to enrolment * Evidence of severe or uncontrolled systemic diseases (e.g. ongoing infection, respiratory, cardiac, hepatic or psychiatric conditions) which in the Investigator's opinion would compromise the protocol objectives
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability: Frequency and Severity of Adverse Events (CTCAE v4.03) | 12 weeks | Safety and tolerability of Betalutin in combination with rituximab as determined by the frequency and severity of adverse events (CTCAE v4.03) in the first 12 weeks after Betalutin |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Preliminary Anti-tumour Activity | 25 months | Best overall response of combination treatment using tumour responses based on CT and PET/CT imaging (classified as as complete response, partial response, no response/stable disease or progressive disease as described in Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification) |
Countries
Czechia, Norway
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 10 MBq/kg Betalutin With Rituximab Treatment 10 MBq/kg Betalutin administered with lilotomab pre-dose on day 0; rituximab administered weekly x 4 doses from day 7, then every 3 months for 2 years
10 MBq/kg Betalutin: 10 MBq/kg Betalutin, lilotomab 40mg, rituximab 375 mg/m2 | 4 |
| 15 MBq/kg Betalutin With Rituximab Treatment 15 MBq/kg Betalutin administered with lilotomab pre-dose on day 0; rituximab administered weekly x 4 doses from day 7, then every 3 months for 2 years
15 MBq/kg Betalutin: 15 MBq/kg Betalutin, lilotomab 40mg, rituximab 375 mg/m2 | 3 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Progressive disease | 0 | 2 |
Baseline characteristics
| Characteristic | 10 MBq/kg Betalutin With Rituximab Treatment | 15 MBq/kg Betalutin With Rituximab Treatment | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 3 Participants | 7 Participants |
| Region of Enrollment Czechia | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Norway | 4 participants | 2 participants | 6 participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 3 |
| other Total, other adverse events | 4 / 4 | 3 / 3 |
| serious Total, serious adverse events | 3 / 4 | 0 / 3 |
Outcome results
Primary
Safety and Tolerability: Frequency and Severity of Adverse Events (CTCAE v4.03)
Safety and tolerability of Betalutin in combination with rituximab as determined by the frequency and severity of adverse events (CTCAE v4.03) in the first 12 weeks after Betalutin
Time frame: 12 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 10 MBq/kg Betalutin With Rituximab Treatment | Safety and Tolerability: Frequency and Severity of Adverse Events (CTCAE v4.03) | Number of participants with adverse events in the first 12 weeks | 3 Participants |
| 10 MBq/kg Betalutin With Rituximab Treatment | Safety and Tolerability: Frequency and Severity of Adverse Events (CTCAE v4.03) | Number of participants with Betalutin related adverse events in the first 12 weeks | 1 Participants |
| 10 MBq/kg Betalutin With Rituximab Treatment | Safety and Tolerability: Frequency and Severity of Adverse Events (CTCAE v4.03) | Number of participants with SAEs in the first 12 weeks | 0 Participants |
| 10 MBq/kg Betalutin With Rituximab Treatment | Safety and Tolerability: Frequency and Severity of Adverse Events (CTCAE v4.03) | Number of participants with CTCAE Grade 3 or 4 adverse events in the first 12 weeks | 2 Participants |
| 10 MBq/kg Betalutin With Rituximab Treatment | Safety and Tolerability: Frequency and Severity of Adverse Events (CTCAE v4.03) | Number of participants with dose limiting toxicities in the first 12 weeks | 0 Participants |
| 15 MBq/kg Betalutin With Rituximab Treatment | Safety and Tolerability: Frequency and Severity of Adverse Events (CTCAE v4.03) | Number of participants with CTCAE Grade 3 or 4 adverse events in the first 12 weeks | 2 Participants |
| 15 MBq/kg Betalutin With Rituximab Treatment | Safety and Tolerability: Frequency and Severity of Adverse Events (CTCAE v4.03) | Number of participants with dose limiting toxicities in the first 12 weeks | 0 Participants |
| 15 MBq/kg Betalutin With Rituximab Treatment | Safety and Tolerability: Frequency and Severity of Adverse Events (CTCAE v4.03) | Number of participants with adverse events in the first 12 weeks | 3 Participants |
| 15 MBq/kg Betalutin With Rituximab Treatment | Safety and Tolerability: Frequency and Severity of Adverse Events (CTCAE v4.03) | Number of participants with SAEs in the first 12 weeks | 0 Participants |
| 15 MBq/kg Betalutin With Rituximab Treatment | Safety and Tolerability: Frequency and Severity of Adverse Events (CTCAE v4.03) | Number of participants with Betalutin related adverse events in the first 12 weeks | 3 Participants |
Secondary
Preliminary Anti-tumour Activity
Best overall response of combination treatment using tumour responses based on CT and PET/CT imaging (classified as as complete response, partial response, no response/stable disease or progressive disease as described in Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification)
Time frame: 25 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 10 MBq/kg Betalutin With Rituximab Treatment | Preliminary Anti-tumour Activity | Complete response | 3 Participants |
| 10 MBq/kg Betalutin With Rituximab Treatment | Preliminary Anti-tumour Activity | Partial response | 1 Participants |
| 15 MBq/kg Betalutin With Rituximab Treatment | Preliminary Anti-tumour Activity | Complete response | 2 Participants |
| 15 MBq/kg Betalutin With Rituximab Treatment | Preliminary Anti-tumour Activity | Partial response | 1 Participants |