Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05991388




Registration number
NCT05991388
Ethics application status
Date submitted
24/07/2023
Date registered
14/08/2023
Date last updated
8/11/2024

Titles & IDs
Public title
A Global Study of Novel Agents in Paediatric and Adolescent Relapsed and Refractory B-cell Non-Hodgkin Lymphoma
Scientific title
A Global Study of Novel Agents in Paediatric and Adolescent Relapsed and Refractory B-cell Non-Hodgkin Lymphoma
Secondary ID [1] 0 0
ITCC-100
Secondary ID [2] 0 0
RG_21-124
Universal Trial Number (UTN)
Trial acronym
Glo-BNHL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
B-cell Non Hodgkin Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Odronextamab
Treatment: Drugs - Loncastuximab tesirine
Treatment: Drugs - Rituximab
Treatment: Drugs - Ifosfamide
Treatment: Drugs - Carboplatin
Treatment: Drugs - Etoposide
Treatment: Drugs - Etoposide Phosphate
Treatment: Drugs - Dexamethasone
Treatment: Other - CAR T-cells (TBC)

Experimental: Treatment Arm I - BsAb - Odronextamab - Patients will receive odronextamab given as an intravenous infusion weekly for 12 weeks, then every two weeks until nine months, and every four weeks thereafter until progression or for a maximum of two years

Experimental: Treatment Arm II - ADC with Standard Chemotherapy - Loncastuximab tesirine with modified R-ICE - Patients will receive loncastuximab tesirine given as a 30-minute intravenous infusion with each cycle of modified R-ICE (maximum three cycles)

Experimental: Treatment Arm III - CAR T-cells - TBC - Patients will receive CAR-T cell therapy - agent TBC


Treatment: Drugs: Odronextamab
CD20xCD3 bispecific antibody

Treatment: Drugs: Loncastuximab tesirine
CD-19-directed antibody-drug conjugate

Treatment: Drugs: Rituximab
Modified R-ICE chemotherapy

Treatment: Drugs: Ifosfamide
Modified R-ICE chemotherapy

Treatment: Drugs: Carboplatin
Modified R-ICE chemotherapy

Treatment: Drugs: Etoposide
Modified R-ICE chemotherapy

Treatment: Drugs: Etoposide Phosphate
Modified R-ICE (Treatment Arm II)

Treatment: Drugs: Dexamethasone
Modified R-ICE chemotherapy

Treatment: Other: CAR T-cells (TBC)
Modified R-ICE chemotherapy
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Treatment Arm I: BsAb: Occurrence of an objective response (OR)
Timepoint [1] 0 0
At the end of week 12 of treatment
Primary outcome [2] 0 0
Treatment Arm II: ADC with standard chemotherapy: Occurrence of CR
Timepoint [2] 0 0
At the end of Cycle 2 and Cycle 3 of treatment (each cycle is 28 days)
Secondary outcome [1] 0 0
Event-free survival time (EFS)
Timepoint [1] 0 0
From start of treatment until last patient has been followed up for 2 years
Secondary outcome [2] 0 0
Progression-free survival time (PFS)
Timepoint [2] 0 0
From start of treatment until last patient has been followed up for 2 years
Secondary outcome [3] 0 0
Overall survival time (OS)
Timepoint [3] 0 0
From start of treatment until last patient has been followed up for 2 years
Secondary outcome [4] 0 0
Best overall response (BOR) during treatment
Timepoint [4] 0 0
At the end of weeks 4, 8, and 12 for Treatment Arm I; at the end of cycles 1, 2, and 3 for Treatment Arm II (each cycle is 28 days)
Secondary outcome [5] 0 0
Duration of response (DOR)
Timepoint [5] 0 0
From start of treatment until last patient has been followed up for 2 years
Secondary outcome [6] 0 0
Occurrence of an objective response (OR), where relevant
Timepoint [6] 0 0
At the end of cycles 1, 2, and 3 (each cycle is 28 days)
Secondary outcome [7] 0 0
Occurrence of adverse events of special interest (AESI)
Timepoint [7] 0 0
From start of treatment until 90 days after last day of treatment
Secondary outcome [8] 0 0
Occurrence of treatment emergent adverse events (TEAEs), where relevant
Timepoint [8] 0 0
From start of treatment until 90 days after last dose

Eligibility
Key inclusion 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.
Minimum age
No limit
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/05/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/05/2033
Actual
Sample size
Target
210
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United Kingdom
State/province [1] 0 0
Birmingham
Country [2] 0 0
United Kingdom
State/province [2] 0 0
Bristol
Country [3] 0 0
United Kingdom
State/province [3] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Other
Name
University of Birmingham
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Cancer Research UK
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Fight Kids Cancer
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Commercial sector/industry
Name [3] 0 0
Regeneron Pharmaceuticals
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Commercial sector/industry
Name [4] 0 0
ADC Therapeutics S.A.
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Amos Burke
Address 0 0
University of Birmingham
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Ellie Williams
Address 0 0
Country 0 0
Phone 0 0
+44 (0)121 414 8040
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT05991388