Trial Title:
A Global Study of Novel Agents in Paediatric and Adolescent Relapsed and Refractory B-cell Non-Hodgkin Lymphoma
NCT ID:
NCT05991388
Condition:
B-cell Non Hodgkin Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Dexamethasone
Rituximab
Loncastuximab tesirine
Carboplatin
Etoposide
Etoposide phosphate
Ifosfamide
Study type:
Interventional
Study phase:
Phase 2/Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Platform trial
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Odronextamab
Description:
CD20xCD3 bispecific antibody
Arm group label:
Treatment Arm I - BsAb - Odronextamab
Other name:
REGN-1979
Intervention type:
Drug
Intervention name:
Loncastuximab tesirine
Description:
CD-19-directed antibody-drug conjugate
Arm group label:
Treatment Arm II - ADC with Standard Chemotherapy - Loncastuximab tesirine with modified R-ICE
Other name:
ADCT-402
Intervention type:
Drug
Intervention name:
Rituximab
Description:
Modified R-ICE chemotherapy
Arm group label:
Treatment Arm II - ADC with Standard Chemotherapy - Loncastuximab tesirine with modified R-ICE
Intervention type:
Drug
Intervention name:
Ifosfamide
Description:
Modified R-ICE chemotherapy
Arm group label:
Treatment Arm II - ADC with Standard Chemotherapy - Loncastuximab tesirine with modified R-ICE
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
Modified R-ICE chemotherapy
Arm group label:
Treatment Arm II - ADC with Standard Chemotherapy - Loncastuximab tesirine with modified R-ICE
Intervention type:
Drug
Intervention name:
Etoposide
Description:
Modified R-ICE chemotherapy
Arm group label:
Treatment Arm II - ADC with Standard Chemotherapy - Loncastuximab tesirine with modified R-ICE
Intervention type:
Drug
Intervention name:
Etoposide Phosphate
Description:
Modified R-ICE (Treatment Arm II)
Arm group label:
Treatment Arm II - ADC with Standard Chemotherapy - Loncastuximab tesirine with modified R-ICE
Intervention type:
Drug
Intervention name:
Dexamethasone
Description:
Modified R-ICE chemotherapy
Arm group label:
Treatment Arm II - ADC with Standard Chemotherapy - Loncastuximab tesirine with modified R-ICE
Intervention type:
Biological
Intervention name:
CAR T-cells (TBC)
Description:
Modified R-ICE chemotherapy
Arm group label:
Treatment Arm III - CAR T-cells - TBC
Summary:
The Glo-BNHL trial is trying to find better medicines for children and young people with
B-cell non-Hodgkin Lymphoma (B-NHL) that does not go away (refractory B-NHL) or does but
comes back again (relapsed B-NHL). B-NHL is a type of cancer that develops inside or
outside of lymph nodes (glands) and organs such as the liver or spleen. Examples of B-NHL
are Burkitt Lymphoma and Diffuse Large B Cell Lymphoma, which may be other names used to
describe this type of cancer. It is very difficult to cure relapsed or refractory B-NHL.
The medicines used now are very powerful with many side effects and only cure around 30
in every 100 children treated. It is very important that investigators quickly find
better medicines for these children and young people.
The Glo-BNHL trial will include three groups of children and young people, each given a
new medicine (either alone or with chemotherapy). The investigators are looking to make
sure the new medicines are safe and that they work to treat the cancer. If the medicine
in one group does not work for a child in the trial, then they may be able to join a
different group to have another new medicine.
Experts from around the world will carefully pick the medicines most likely to be helpful
to be part of the trial. If one of the new medicines seems not to be working as well as
hoped then the investigators will take it out of the trial as soon as possible. This will
let other new medicines be added to the trial and tested. If a medicine does seem to be
working well, then it will continue in the trial to make sure it really is the most
useful medicine available.
Children from around the world will be invited to take part in the trial. The
investigators will then check on them for at least two years after they finish the trial
treatment to look for possible side effects of the new medicine.
Detailed description:
Glo-BNHL is an adaptive prospective international multicentre platform clinical trial
designed to evaluate the safety and efficacy of novel agents for the treatment of
children, adolescents, and young adults with relapsed and/or refractory B-cell
non-Hodgkin Lymphoma (r/r BNHL). The trial is designed to generate sufficient evidence to
potentially be practice-changing in this rare cancer setting. With the trial
incorporating an initial stage evaluating efficacy followed potentially by an expansion
stage to provide confirmatory analysis, the trial could be considered to be phase II/III.
Novel agents will be prioritised for inclusion in the platform according to an
overarching prioritisation list and a robust systematic scientific assessment, performed
by the international Trial Steering Committee (TSC).
The platform consists of three parallel treatment arms, each one investigating a
different novel agent in a group of patients. The platform allows the testing of a
pipeline of novel agents in each treatment arm consecutively. Patients in the platform
may be enrolled into any of the available treatment arms for which they are eligible. The
classes of novel agents prioritised for inclusion at the initiation of the trial are:
- Treatment Arm I: Bispecific antibodies (BsAbs)
- Treatment Arm II: Antibody-drug conjugates (ADC) with standard chemotherapy
- Treatment Arm III: Chimeric antigen receptor (CAR) T-cells
The platform trial has an adaptive Bayesian design that facilitates efficient GO/NoGO
decisions relevant to the target population enrolled in each treatment arm. The Bayesian
approach estimates the probability that a novel agent is clinically effective and enables
decision-making even with small numbers of patients. It can also incorporate prior
knowledge, thereby maximising the utility of all available data in this rare population.
It facilitates continuous evaluation of any novel agent as the sample size increases.
Furthermore it allows for the discontinuation of an agent if the observed trial data
demonstrate a high probability that the novel agent is ineffective at any time, allowing
the next agent in the pipeline to be introduced. If the prioritisation of classes of
novel agents by the TSC changes, treatment arms can be amended, added, or removed to
reflect this. Not all Treatment Arms will necessarily be open to recruitment at all
times.
Criteria for eligibility:
Criteria:
Inclusion criteria applicable to all treatment arms:
- Histologically proven mature B-NHL (Diffuse Large B-Cell Lymphoma (DLBCL), Burkitt
Lymphoma/Leukaemia or atypical Burkitt/Burkitt-like lymphoma, primary mediastinal
large B-cell lymphoma (PMLBL), and mature B-NHL/Not Otherwise Specified (NOS)) at
initial diagnosis
- Radiologically and/or histologically proven B-NHL in first relapse (only one prior
line of therapy) or subsequent relapse (more than one prior line of therapy) or
refractory(*) B-NHL. (Note: relapses following prior targeted therapy must have
continuing target positivity, confirmed by an established method).
- If relapse occurs more than two years after previous therapy, a biopsy must be
performed
- Evaluable disease as per the international paediatric non-Hodgkin Lymphoma response
criteria, including:
- at least one bi-dimensionally measurable nodal lesion >1.5 cm in its longest
dimension;
- or at least one bi-dimensionally measurable extra-nodal lesion >1.0 cm in its
longest dimension on computerised tomography (CT) or Magnetic Resonance Imaging
(MRI);
- or bone marrow involvement (≥25% involvement from bone marrow, if only site of
disease. Any standard method of assessment is acceptable i.e. cytomorphology,
flow cytometry and/or immunohistochemistry);
- or, dependent on treatment arm, evaluable Central Nervous System (CNS) only
disease (evaluable by imaging or Cerebrospinal Fluid (CSF) analysis)(**)
- Age from birth to ≤25 years old at the time of trial entry
- Performance status ≥50 using Karnofsky or Lansky performance scores
- Life expectancy of ≥8 weeks
- Adequate bone marrow function documented by:
- Platelet count ≥50x 10^9/L (no platelet transfusion therapy within seven days
prior to treatment) unless bone marrow involvement(***)
- Absolute neutrophil count (ANC) ≥0.75 x 10^9/L (no granulocyte colony
stimulating factor within 2 days prior to treatment) unless bone marrow
involvement(***)
- Adequate hepatic function documented by:
- Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤5 x
upper limit of normal (ULN)
- Total bilirubin ≤1.5 X ULN ***Patients with known Gilbert syndrome will be
excluded if the total bilirubin value is >4 x ULN for the local general
population
- Documented negative pregnancy test for female patients of childbearing potential
within seven days prior to trial entry
- Patients of reproductive potential agrees to use effective contraception whilst on
trial treatment and for 12 months following treatment discontinuation
- Written informed consent given by patient and/or parents/legal representative
Inclusion criteria applicable to treatment arm I only:
- Male patients of reproductive potential must agree not to donate sperm whilst on
trial treatment and for 6 months following treatment discontinuation
- Adequate renal function, creatinine clearance >45 ml/min by measurement or
estimation (if creatinine levels are normal for the patient's age, using the
Cockroft-Gault Equation is sufficient)
- For patients with bone marrow involvement(***) or splenic sequestration, adequate
bone marrow function documented by:
- Platelet count ≥25 x 10^9/L (no platelet transfusion therapy within three days
prior to treatment)
- Haemoglobin level ≥7 g/dL
- Absolute neutrophil count (ANC) ≥0.5 x 10^9/L (no granulocyte colony
stimulating factor within two days prior to treatment)
- Patients who have received CAR T-cell therapy or other cellular therapies more than
28 days prior must demonstrate recovery from acute toxicities and have measurable
disease
Inclusion criteria applicable to treatment arm II only:
- Adequate renal function, by measured glomerular filtration rate (GFR) >60
ml/min/1.73m^2 (estimated GFR is not sufficient)
- For patients with bone marrow involvement(***) or splenic sequestration,
requirements for bone marrow function do not apply
(*) Refractory disease
The following patients are considered to have refractory disease and can be included in
this trial:
- Patients with who do not achieve PR or CR with last therapy
- Patients with partial response to last therapy (biopsy proven), with no evidence of
progression
(**) CNS only disease Patients with CNS only disease may be eligible depending on the
treatment arm. Please refer to the relevant treatment arm specific eligibility criteria.
(***) Bone marrow involvement Patients who have ≥ 25% blasts in the bone marrow are
considered to have bone marrow involvement. For these patients, requirements for bone
marrow function are dependent on treatment arm. Please refer to the relevant treatment
arm specific eligibility criteria.
Exclusion Criteria:
- B-cell Acute Lymphoblastic Leukaemia (B-ALL)/B-cell Lymphoblastic Lymphoma (B-LBL)
- Patients within:
- 90 days after an allogenic HSCT procedure
- 45 days after an autologous HSCT procedure
- 28 days of experiencing graft versus host disease (GvHD) requiring systemic
therapy, and/or immunosuppressive treatment
- 14 days of previous investigational treatment
- 28 days of receiving craniospinal radiation; or 14 days of any other radiation
- For patients who have received any CAR T-cell therapy or other cellular
therapies, see treatment arm specific eligibility criteria
- Patients who have ongoing acute toxicities from most recent lymphoma directed
therapy
- Patients with known DNA repair disorder or known primary immunodeficiency
- Patients who are pregnant or breastfeeding (exclusively or partially)
- Patients who cannot regularly be followed up in accordance with the protocol due to
psychological, social, geographical or other issues
- Patients for whom non-compliance with treatment or trial procedures is expected
- Uncontrolled concomitant infection. Severe infection (such as sepsis, pneumonia,
etc.) should be clinically controlled at the time of trial entry
- Known HIV positivity
- Hepatitis B carrier status, history of Hepatitis B Virus or positive serology. A
patient is considered as a Hepatitis B Virus carrier or to have (had) Hepatitis B
Virus infection in case of:
- Unimmunized and HBsAg and/or anti-HBs antibody and/or anti- HBc antibody
positive,
- Immunized and HBsAg and/or anti-HBc antibody positive.
- Live vaccine within 28 days prior to trial entry
- Known history of hypersensitivity to any of the treatments or excipients
Exclusion criteria applicable to treatment arm I only:
- Central Nervous System (CNS) only disease
- Patients within 28 days of any CAR-T cell therapy or other cellular therapies
- Left ventricular shortening fraction (LVSF) <27% or left ventricular ejection
fraction (LVEF) <50%, as determined by ECHO or MUGA, any evidence of pericardial
effusion (except trace or physiological) as determined by an ECHO, and any
clinically significant arrhythmias
- Known CD20 negative disease at initial diagnosis
- Seizure within the last 12 months
- Prior treatment with CD20 x CD3 bispecific therapy
- Known hypersensitivity to both allopurinol and rasburicase
Exclusion criteria applicable to treatment arm II only:
- Patients within 42 days of any CAR-T cell therapy or other cellular therapies
- Clinically significant (Grade ≥2) third space fluid accumulation (i.e., ascites
requiring drainage or pleural effusion that is either requiring drainage or
associated with shortness of breath)
- Steroid treatment for more than a total of seven days in the 14 days prior to trial
entry
Gender:
All
Minimum age:
N/A
Maximum age:
25 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Birmingham Children's Hospital
Address:
City:
Birmingham
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Amos Burke
Facility:
Name:
Bristol Royal Hospital for Children
Address:
City:
Bristol
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Emma Seaford
Facility:
Name:
Royal Manchester Children's Hospital
Address:
City:
Manchester
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Guy Makin
Start date:
May 2, 2024
Completion date:
May 1, 2033
Lead sponsor:
Agency:
University of Birmingham
Agency class:
Other
Collaborator:
Agency:
Cancer Research UK
Agency class:
Other
Collaborator:
Agency:
Fight Kids Cancer
Agency class:
Other
Collaborator:
Agency:
Regeneron Pharmaceuticals
Agency class:
Industry
Collaborator:
Agency:
ADC Therapeutics S.A.
Agency class:
Industry
Source:
University of Birmingham
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05991388
