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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04759586




Registration number
NCT04759586
Ethics application status
Date submitted
17/02/2021
Date registered
18/02/2021

Titles & IDs
Public title
Nivolumab in Combination With Chemo-Immunotherapy for the Treatment of Newly Diagnosed Primary Mediastinal B-Cell Lymphoma
Scientific title
A Randomized Phase 3 Trial of Nivolumab (NSC# 748726) in Combination With Chemo-Immunotherapy for the Treatment of Newly Diagnosed Primary Mediastinal B-Cell Lymphoma
Secondary ID [1] 0 0
NCI-2021-01071
Secondary ID [2] 0 0
NCI-2021-01071
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Primary Mediastinal Large B-Cell 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: Surgery - Biospecimen Collection
Treatment: Surgery - Bone Marrow Aspiration
Treatment: Surgery - Bone Marrow Biopsy
Treatment: Surgery - Computed Tomography
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Doxorubicin Hydrochloride
Treatment: Surgery - Echocardiography
Treatment: Drugs - Etoposide Phosphate
Treatment: Other - Filgrastim
Treatment: Surgery - Lumbar Puncture
Treatment: Other - Nivolumab
Treatment: Other - Pegfilgrastim
Treatment: Surgery - Positron Emission Tomography
Treatment: Drugs - Prednisolone
Treatment: Drugs - Prednisone
Treatment: Other - Radiation Therapy
Treatment: Other - Rituximab
Treatment: Other - Rituximab and Hyaluronidase Human
Treatment: Drugs - Vincristine Sulfate

Active comparator: Arm A (DA-EPOCH-R) - See Detailed Description

Experimental: Arm B (DA-EPOCH-R, nivolumab) - Patients receive treatment as in Arm A. Patients also receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles (5 if the patient had 1 prior cycle of treatment) in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO and LP for CSF collection during screening. Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study.

Active comparator: Arm C (R-CHOP) - Patients receive prednisone or prednisolone PO QD on days 1-5 and rituximab IV or rituximab and hyaluronidase human SC over 5 minutes on day 1 or 5. Patients also receive cyclophosphamide IV over 30-60 minutes, doxorubicin hydrochloride IV over 1-15 minutes or up to 60 minutes, and vincristine sulfate IV over 1 or up to 60 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles (5 if the patient had 1 prior cycle of treatment) in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study.

Experimental: Arm D (R-CHOP, nivolumab) - Patients receive treatment as in Arm C. Patients also receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles (5 if the patient had 1 prior cycle of treatment) in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study.

Active comparator: Arm E (R-CHOP, radiation therapy) - Patients receive treatment as in Arm C. Within 6-8 weeks after completion of chemotherapy, patients undergo radiation therapy over 25 fractions. Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study.

Experimental: Arm F (R-CHOP, nivolumab, radiation therapy) - Patients receive treatment as in Arm D. Within 6-8 weeks after completion of chemotherapy, patients undergo radiation therapy over 25 fractions. Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study.


Treatment: Surgery: Biospecimen Collection
Undergo blood and CSF sample collection

Treatment: Surgery: Bone Marrow Aspiration
Undergo bone marrow biopsy and aspiration

Treatment: Surgery: Bone Marrow Biopsy
Undergo bone marrow biopsy and aspiration

Treatment: Surgery: Computed Tomography
Undergo CT or PET/CT

Treatment: Drugs: Cyclophosphamide
Given IV

Treatment: Drugs: Doxorubicin Hydrochloride
Given IV

Treatment: Surgery: Echocardiography
Undergo ECHO

Treatment: Drugs: Etoposide Phosphate
Given IV

Treatment: Other: Filgrastim
Given SC

Treatment: Surgery: Lumbar Puncture
Undergo LP

Treatment: Other: Nivolumab
Given IV

Treatment: Other: Pegfilgrastim
Given SC

Treatment: Surgery: Positron Emission Tomography
Undergo PET/CT

Treatment: Drugs: Prednisolone
Given PO

Treatment: Drugs: Prednisone
Given PO

Treatment: Other: Radiation Therapy
Undergo radiation therapy

Treatment: Other: Rituximab
Given IV

Treatment: Other: Rituximab and Hyaluronidase Human
Given SC

Treatment: Drugs: Vincristine Sulfate
Given IV
Intervention code [1] 0 0
Treatment: Surgery
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free survival (PFS)
Timepoint [1] 0 0
From enrollment on the study to first occurrence of relapse/progression or death, assessed up to 7 years
Secondary outcome [1] 0 0
Efficacy-related event-free survival
Timepoint [1] 0 0
Up to 7 years
Secondary outcome [2] 0 0
Therapy-related event-free survival
Timepoint [2] 0 0
Up to 7 years
Secondary outcome [3] 0 0
Overall survival
Timepoint [3] 0 0
Up to 7 years
Secondary outcome [4] 0 0
Proportion of positive positron emission tomography (PET) scans
Timepoint [4] 0 0
Up to 6 cycle (1 cycle = 21 days)

Eligibility
Key inclusion criteria
* Age >= 2 years
* Patient must have histologically confirmed primary mediastinal B-cell lymphoma (PMBCL) as defined by World Health Organization (WHO) criteria
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 or ECOG performance status of 3 if poor performance is related to lymphoma

* Children's Oncology Group (COG) Institutions: Use Karnofsky for patients >= 17 and < 18 years of age and Lansky for patients < 17 years of age
* Adults (age 18 or older): Creatinine clearance >= 30 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on actual body weight
* Pediatric Patients (age < 18 years): The following must have been obtained within 14 days prior to registration:

* Measured or calculated (based on institutional standard) creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2, or
* Serum creatinine =< 1.5 x institutional upper limit of normal (IULN), or a serum creatinine based on age/gender as follows:

* Age : 2 to < 6 year; Maximum serum creatinine (mg/dL): 0.8 (male; 0.8 (female)
* Age : 6 to < 10 years; Maximum serum creatinine (mg/dL): 1 (male); 1 (female)
* Age : 10 to < 13 years; Maximum serum creatinine (mg/dL): 1.2 (male); 1.2 (female)
* Age : 13 to < 16 years; Maximum serum creatinine (mg/dL): 1.5 (male); 1.4 (female)
* Age : >= 16 years to < 18 years; Maximum serum creatinine (mg/dL): 1.7 (male); 1.4 (female)
* Patients with abnormal liver function will be eligible to enroll if the lab abnormality is thought to be due to the lymphoma or Gilbert's syndrome
* Age >= 18 years: Ejection fraction of >= 50% by echocardiogram
* Age < 18 years: Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by radionuclide angiogram
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Minimum age
2 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Administration of prior anti-cancer therapy except as outlined below:

* A short course (=< 2 weeks) of corticosteroids for the relief of lymphoma-related symptoms
* A single course of COP (cyclophosphamide, vincristine, and prednisone)
* One cycle of chemo-immunotherapy including R-CHOP, DA-EPOCH-R, a pediatric mature B-cell non-Hodgkin lymphoma (B-NHL) induction therapy (such as ANHL1131), or intrathecal chemotherapy that has not started more than 21 days prior to enrollment
* Active ischemic heart disease or heart failure
* Active uncontrolled infection
* Central nervous system (CNS) involvement of lymphoma
* Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with safety or efficacy assessment of this trial
* Active autoimmune disease that has required systemic treatment (such as disease modifying agents, corticosteroids, or immunosuppressive agents) in the past 2 years. Replacement therapy such as thyroxine, insulin or physiologic corticosteroid for adrenal or pituitary insufficiency is not considered a form of systemic treatment
* In patients < 18 years of age hepatitis B serologies consistent with past or current infections
* Patients with severe hepatic impairment (Child-Pugh class C or serum total bilirubin > 5.0 mg/dL) unless thought to be due to lymphoma or Gilbert's syndrome
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
* Sexually active patients of reproductive potential who have not agreed to use a highly effective contraceptive method (failure rate of < 1% per year when used consistently and correctly) for the duration of their study participation
* Lactating females are not eligible unless they have agreed not to breastfeed their infants starting with the first dose of study therapy and for at least 6 months after the last dose of rituximab

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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 3
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
5/10/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/09/2027
Actual
Sample size
Target
244
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
John Hunter Children's Hospital - Hunter Regional Mail Centre
Recruitment hospital [2] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [3] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [4] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [5] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
2310 - Hunter Regional Mail Centre
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
3052 - Parkville
Recruitment postcode(s) [5] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
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Alaska
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Arizona
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Arkansas
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California
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Colorado
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Connecticut
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Delaware
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District of Columbia
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Florida
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Georgia
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Hawaii
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Idaho
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Illinois
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Indiana
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Iowa
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Kentucky
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Louisiana
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Maine
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Massachusetts
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Michigan
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New Mexico
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New York
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North Carolina
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North Dakota
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Ohio
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Oregon
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Pennsylvania
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South Carolina
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South Dakota
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Tennessee
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Utah
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West Virginia
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Wisconsin
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Canada
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Alberta
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Canada
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Manitoba
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Canada
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Newfoundland and Labrador
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Canada
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Nova Scotia
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Canada
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Ontario
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Quebec
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Puerto Rico
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Caguas

Funding & Sponsors
Primary sponsor type
Government body
Name
National Cancer Institute (NCI)
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Lisa G Roth
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://grants.nih.gov/policy/sharing.htm


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/NCT04759586