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Aggressive Non-Hodgkin LymphomaPhase 1/2NCT03704714

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

A Phase 1/2 study testing Cyclophosphamide, Doxorubicin Hydrochloride and Nivolumab in people with Aggressive Non-Hodgkin Lymphoma and B-Cell Non-Hodgkin Lymphoma, run by Northwestern University at 4 sites in United States.

Suspended

Paused. Enrolment is on hold for now and may resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cyclophosphamide, Doxorubicin Hydrochloride and Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
4 sitesUnited States
Study dates
20 Nov 2018to 11 Jun 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • Females of child-bearing potential (FOCBP) and men who are sexually active with FOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment and the designated post-treatment period.
  • NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
  • Has not undergone a hysterectomy or bilateral oophorectomy.
  • Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months).
  • Females of childbearing potential (FOCBP) must have a negative urine or serum pregnancy test within 7 days prior to registration on study.
  • Patients must have the ability to understand and willingness to sign a written informed consent prior to registration on study.

Who cannot join

  • 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.
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  • 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:
  • Ongoing or active systemic infection.
  • Symptomatic congestive heart failure.
  • Myocardial infarction within 6 months prior to registration.
  • Unstable angina pectoris.
  • Uncontrolled or symptomatic cardiac arrhythmias.
  • Any class 3 (moderate) or class 4 (severe) cardiac disease as defined by the New York Heart Association Functional classification.
  • Psychiatric illness/social situations that would limit compliance with study requirements.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Northwestern University

    Chicago, Illinois, 60611

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • Northwestern University- Lake Forest Hospital

    Lake Forest, Illinois, 60045

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

    Warrenville, Illinois, 60555

Other trials in United States

About this study

Official title: Phase I/II Study to Evaluate the Safety and Efficacy of Nivolumab in Combination With R-CHOP in a Cohort of Patients With DLBCL/tFL/ High Grade B-NHL

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To identify the maximum tolerated dose (MTD) for the combination treatment of nivolumab and rituximab, cyclophosphamide, doxorubicin hydrochloride (doxorubicin), vincristine sulfate (vincristine), and prednisone (R-CHOP) in patients with diffuse large B-cell lymphoma (DLBCL). (Phase I) II. To assess the impact of nivolumab + R-CHOP on response by looking at complete response (CR) rates. (Phase II)

SECONDARY OBJECTIVES:

  1. To look at preliminary efficacy as measured by overall response rate for combination nivolumab + R-CHOP.

II. To assess the impact of nivolumab + R-CHOP on survival outcomes, specifically progression-free survival (PFS), overall survival (OS) and event-free-survival (EFS).

III. To assess toxicity and tolerability of patients treated with nivolumab + R-CHOP.

IV. To assess quality of life in patients treated with nivolumab + R-CHOP.

EXPLORATORY OBJECTIVES:

  1. To explore the impact of the PD-1:PD-L1 regulatory axis and targeting this axis on the immune microenvironment.

II. To identify the process of cachexia as a potential mechanism of resistance to anti-PD-1 therapy.

OUTLINE: This is a phase I, dose-escalation study of nivolumab followed by a phase II study.

Participants receive nivolumab intravenously (IV) over 30 minutes on day 1. Participants also receive 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 orally (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.

After completion of study treatment, participants are followed for up to 18 months.

Being tested
Cyclophosphamide, Doxorubicin Hydrochloride, Nivolumab, Prednisone, Quality-of-Life Assessment
Medical subject headings
Lymphoma, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • Doxorubicin HydrochlorideDrug

    Also called 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

    Given IV

  • NivolumabBiological

    Also called BMS-936558, MDX-1106, NIVO, ONO-4538

    Given IV

  • PrednisoneDrug

    Also called .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl

    Given PO

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • RituximabBiological

    Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody

    Given IV

  • Vincristine SulfateDrug

    Also called Kyocristine, Leurocristine sulfate, Leurocristine, sulfate, Oncovin

    Given IV

Study groups in NCT03704714
Study groupRoleWhat they receive
Treatment (nivolumab and R-CHOP)ExperimentalParticipants 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.
Receives: Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Biological: Nivolumab; Drug: Prednisone; Other: Quality-of-Life Assessment; Biological: Rituximab; Drug: Vincristine Sulfate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 18 months

  2. 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.

    Measured: At 18 months

Secondary outcomes (7)

  1. Overall response rate (ORR)

    Will be defined as the percentage of subjects with a confirmed complete response (CR) or partial response (PR) as assessed by the investigators using Lugano criteria.

    Measured: Up to 18 months

  2. Overall survival (OS) rate

    OS rate at 18 months: OS will be measured from the date of enrollment to the date of death from any cause.

    Measured: At 18 months

  3. Event-free survival (EFS)

    EFS rate at 18 months: EFS will be measured from the date of enrollment to the date of first documented disease progression, relapse, discontinuation of therapy for any reason, initiation of new anti-lymphoma therapy or death from any cause.

    Measured: At 18 months

  4. Overall response rates as defined by the RECIL and LYRIC criteria

    RECIL and LYRIC criteria will be evaluated using scans at baseline.

    Measured: Up to 18 months

  5. Frailty/Geriatric Assessments

    Frailty will be assessed using the Geriatric Assessment Tool as developed by the Cancer and Aging Group and the Fried Frailty Index.

    Measured: Up to 18 months

  6. Incidence of Adverse Events

    Toxicity Assessment: Toxicity will be graded using the CTCAE v5.0 and the pro- CTCAE (patient reported symptoms).

    Measured: Up to 42 days after treatment discontinuation

  7. Quality of life Assessment

    Quality of life with treatment will be measured using Patient Reported Outcomes Measurement Information System (PROMIS) based measures and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C-30).

    Measured: Up to 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Oct 2018
  2. Study start20 Nov 2018
  3. Primary completion11 Dec 2024 (estimated)
  4. Study completion11 Jun 2025 (estimated)

Why it stopped: Protocol being amended for stats/accrual changes as per PI

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03704714
Sponsor's protocol ID
NU 17H08
Other IDs
STU00207793, NU 17H08, P30CA060553, NCI-2018-01666
Status last verified
Aug 2022
First submitted
10 Oct 2018
Last updated
15 Aug 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 40706069

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cyclophosphamide, Doxorubicin Hydrochloride and Nivolumab in people with Aggressive Non-Hodgkin Lymphoma and B-Cell Non-Hodgkin Lymphoma, run by Northwestern University at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: paused, as of the sponsor's last update on 15 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose (MTD) for the combination treatment of nivolumab and R-CHOP (time frame: Up to 18 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03704714, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2022.

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