Nivolumab and Combination Chemotherapy in Treating Participants With Diffuse Large B-Cell Lymphoma

NCT03704714 | Suspended Phase 1 DMC FDA Drug

• 4 other identifiers: NU 17H08STU00207793P30CA060553NCI-2018-01666
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 4

Brief Summary

This phase I/II trial studies the side effects and best dose of nivolumab and how well it works when giving together with combination chemotherapy in treating participants with diffuse large B-cell lymphoma. Monoclonal antibodies, such as nivolumab, interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nivolumab and combination chemotherapy may work better in treating participants with diffuse large B-cell lymphoma.

Conditions

Aggressive Non-Hodgkin Lymphoma; B-Cell Non-Hodgkin Lymphoma; CD20 Positive; Diffuse Large B-Cell Lymphoma Unclassifiable; Intravascular Large B-Cell Lymphoma; Primary Mediastinal (Thymic) Large B-Cell Lymphoma; T-Cell/Histiocyte-Rich Large B-Cell Lymphoma; Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) for the combination treatment of nivolumab and R-CHOP

  To identify the MTD for the combination treatment of nivolumab and R-CHOP in patients with DLBCL, this will be established during Phase I using a modified 3+3 dose escalation.

  Up to 18 months

• Progression Free Survival (PFS)

  To assess the impact of nivolumab + R-CHOP on PFS at 18 months: This will be the proportion of patient that will be alive and progression free at 18 months.

  At 18 months

Secondary Outcomes (7)

• Overall response rate (ORR)

  Up to 18 months

• Overall survival (OS) rate

  At 18 months

• Event-free survival (EFS)

  At 18 months

• Overall response rates as defined by the RECIL and LYRIC criteria

  Up to 18 months

• Frailty/Geriatric Assessments

  Up to 18 months

Study Arms (1)

Treatment (nivolumab and R-CHOP)

EXPERIMENTAL

Participants receive nivolumab IV over 30 minutes on day 1. Participants also rituximab IV on day 2, cyclophosphamide IV on day 2, doxorubicin hydrochloride IV over 3-5 hours on day 2, vincristine sulfate IV over 30 minutes on day 2, and prednisone PO on days 2-6 of course 1 and rituximab IV on day 1, cyclophosphamide IV on day 1, doxorubicin hydrochloride IV over 3-5 hours on day 1, vincristine sulfate IV over 30 minutes on day 1, and prednisone PO on days 1-5 of courses 2-6. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Biological: Nivolumab; Drug: Prednisone; Other: Quality-of-Life Assessment; Biological: Rituximab; Drug: Vincristine Sulfate

Interventions

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (nivolumab and R-CHOP)

Doxorubicin Hydrochloride DRUG

Given IV

Also known as: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin, Adriamycin Hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, hydroxydaunorubicin, Rubex

Treatment (nivolumab and R-CHOP)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Treatment (nivolumab and R-CHOP)

Prednisone DRUG

Given PO

Also known as: .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Lisacort, Meprosona-F, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisonum, Prednitone, Promifen, Servisone, SK-Prednisone

Treatment (nivolumab and R-CHOP)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (nivolumab and R-CHOP)

Rituximab BIOLOGICAL

Given IV

Also known as: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, RTXM83

Treatment (nivolumab and R-CHOP)

Vincristine Sulfate DRUG

Given IV

Also known as: Kyocristine, Leurocristine sulfate, Leurocristine, sulfate, Oncovin, Vincasar, Vincosid, Vincrex, Vincristine, sulfate

Treatment (nivolumab and R-CHOP)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must have a confirmed diagnosis of:
• De novo DLBCL including the clinical subtypes of primary mediastinal, - cell/histiocyte-rich large B-cell lymphoma and intravascular DLBCL OR
• De novo transformed DLBCL from follicular lymphoma (FL) OR
• Any high grade CD20+ B-cell lymphoma per World Health Organization (WHO) 2016 OR
• CD20+ aggressive B-cell lymphoma unclassifiable.
• Patient must be deemed an appropriate candidate for R-CHOP therapy.
• Patients must be naive to prior therapy for the study diagnosis.
• Patient must have advanced stage III/IV early stage disease where provider determines single modality therapy with chemo-immunotherapy is most appropriate (i.e radiation deferred).
• Patient must have measurable disease (defined as \>= 1.5 cm in diameter) with correlated fludeoxyglucose F-18 (FDG)-avidity on positron emission tomography (PET) scan with Deauville score of 4 or 5 at time of diagnosis.
• Patient must have Eastern Cooperative Oncology Group (ECOG) performance status =\< 2.
• Absolute neutrophil count (ANC) \>= 1000/mm\^3, independent of growth factor support or \>= 500/mm\^3 in cases of ongoing bone marrow involvement (in either case, these must be independent of transfusion support) documented =\< 28 days prior to registration.
• Platelets \>= 100,000/mm\^3, or \>= 50,000 in cases of ongoing bone marrow involvement (In either case, these must be independent of transfusion support) documented =\< 28 days prior to registration.
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) documented =\< 28 days prior to registration.
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) /alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SPGT\]) =\< 3 x ULN documented =\< 28 days prior to registration.
• Creatinine clearance \>= 25 mL/min documented =\< 28 days prior to registration.

You may not qualify if:

• Patients who have received prior therapy intended to treat the study diagnosis are not eligible.
• Patients who have received prior anti-PD-1/L1 therapy for any indication are not eligible.
• Patients who require urgent cytoreductive therapy (e.g. surgery or radiation) are not eligible.
• Subjects with known immunodeficiency, known autoimmune disease, or concurrent use of immunomodulatory agents are not eligible.
• Patients who have a condition requiring systemic treatment with corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications =\< 14 days prior to registration are not eligible.
• NOTE: Inhaled steroids and adrenal replacement steroid doses \>10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. A brief (less than 3 weeks) course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction caused by a contact allergen) is permitted.
• Patients with known central nervous system (CNS) involvement are not eligible.
• Patients with an active malignancy requiring therapy such as radiation, chemotherapy, or immunotherapy are not eligible.
• NOTE: Exceptions to this are as follows: localized non-melanotic skin cancer and any cancer that in the judgment of the investigator has been treated with curative intent and will not interfere with the study treatment plan and response assessment. Prostate and breast cancer patients undergoing hormone therapy with no currently active disease are eligible.
• Patients with known human immunodeficiency virus (HIV) are not eligible.
• Patients with clinically active hepatitis A, B, or C infections are not eligible.
• NOTE: Patients with a history of hepatitis may be eligible if they have a normal titer. Such cases should be approved by the study principal investigator (PI).
• Patients who have any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator?s opinion, could compromise the subject?s safety or put the study outcomes at risk are not eligible.
• Pregnant or nursing females are not eligible.
• Patients with uncontrolled intercurrent illness including, but not limited to, any of the following are not eligible:

Sponsors & Collaborators

• Northwestern University: lead
• Bristol-Myers Squibb: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (4)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Northwestern University- Lake Forest Hospital

Lake Forest, Illinois, 60045, United States

Location

Northwestern Medicine: Delnor, DuPage, Warrenville, Kishwaukee (West Region)

Warrenville, Illinois, 60555, United States

Location

Related Publications (1)

• Odetola O, Ma S, Winter J, Pro B, Roy I, Xie P, Zhang B, Chen Q, Koulogeorgas GP, Mi X, Chen R, Ma Y, Tang X, Bayer R, Eisner R, Nelson V, Shaikh H, Tsarwhas D, Saghir F, Venugopal P, Gordon LI, Karmali R. Nivolumab in combination with R-CHOP for treatment-naive diffuse large B-cell lymphoma: an evaluation of safety and efficacy. Blood Adv. 2025 Nov 11;9(21):5616-5625. doi: 10.1182/bloodadvances.2025016298.

  PMID: 40706069 DERIVED

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

Cyclophosphamide; Doxorubicin; Nivolumab; Prednisone; deltacortene; prednylidene; Rituximab; CT-P10; Vincristine

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Antibodies, Monoclonal, Murine-Derived; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Reem Karmali, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2018
• First Posted: October 15, 2018
• Study Start: November 20, 2018
• Primary Completion: December 11, 2024
• Study Completion: June 11, 2025
• Last Updated: August 15, 2022

Record last verified: 2022-08

Locations

US (4)