Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 36 of 66 for:    Behaviors and Mental Disorders[CONDITION-BROWSE-BRANCH] | Recruiting, Not yet recruiting, Available Studies | ( Map: Illinois, United States ) | NIH, U.S. Fed

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

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 evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03704714
Recruitment Status : Recruiting
First Posted : October 15, 2018
Last Update Posted : December 4, 2018
Sponsor:
Collaborators:
Bristol-Myers Squibb (BMS)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Northwestern University

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.

Condition or disease Intervention/treatment Phase
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 Drug: Cyclophosphamide Drug: Doxorubicin Hydrochloride Biological: Nivolumab Drug: Prednisone Other: Quality-of-Life Assessment Biological: Rituximab Drug: Vincristine Sulfate Phase 1 Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. 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:

I. 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:

I. 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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 20, 2018
Estimated Primary Completion Date : May 11, 2021
Estimated Study Completion Date : June 11, 2022


Arm Intervention/treatment
Experimental: Treatment (nivolumab and R-CHOP)
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
Given IV
Other Names:
  • (-)-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

Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
  • 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

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo

Drug: Prednisone
Given PO
Other Names:
  • .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

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Biological: Rituximab
Given IV
Other Names:
  • 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

Drug: Vincristine Sulfate
Given IV
Other Names:
  • Kyocristine
  • Leurocristine sulfate
  • Leurocristine, sulfate
  • Oncovin
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate




Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) for the combination treatment of nivolumab and R-CHOP [ Time Frame: Up to 18 months ]
    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.

  2. Progression Free Survival (PFS) [ Time Frame: At 18 months ]
    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.


Secondary Outcome Measures :
  1. Overall response rate (ORR) [ Time Frame: Up to 18 months ]
    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.

  2. Overall survival (OS) rate [ Time Frame: At 18 months ]
    OS rate at 18 months: OS will be measured from the date of enrollment to the date of death from any cause.

  3. Event-free survival (EFS) [ Time Frame: At 18 months ]
    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.

  4. Overall response rates as defined by the RECIL and LYRIC criteria [ Time Frame: Up to 18 months ]
    RECIL and LYRIC criteria will be evaluated using scans at baseline.

  5. Frailty/Geriatric Assessments [ Time Frame: Up to 18 months ]
    Frailty will be assessed using the Geriatric Assessment Tool as developed by the Cancer and Aging Group and the Fried Frailty Index.

  6. Incidence of Adverse Events [ Time Frame: Up to 42 days after treatment discontinuation ]
    Toxicity Assessment: Toxicity will be graded using the CTCAE v5.0 and the pro- CTCAE (patient reported symptoms).

  7. Quality of life Assessment [ Time Frame: Up to 18 months ]
    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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • 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.

Exclusion Criteria:

  • 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:

    • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03704714


Contacts
Layout table for location contacts
Contact: Study Coordinator (312)695-1301 cancertrials@northwestern.edu

Locations
Layout table for location information
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Reem Karmali, MD    312-695-0990      
Principal Investigator: Reem Karmali, MD         
Rush University Medical Center Not yet recruiting
Chicago, Illinois, United States, 60612
Contact: Parameswaran Venugopal    312-942-5978    Parameswaran_Venugopal@rush.edu   
Principal Investigator: Parameswaran Venugopal         
Northwestern University- Lake Forest Hospital Recruiting
Lake Forest, Illinois, United States, 60045
Contact: Valerie Nelson, MD    847-582-2134      
Principal Investigator: Valerie Nelson, MD         
Sponsors and Collaborators
Northwestern University
Bristol-Myers Squibb (BMS)
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Reem Karmali, MD Northwestern University

Layout table for additonal information
Responsible Party: Northwestern University
ClinicalTrials.gov Identifier: NCT03704714     History of Changes
Other Study ID Numbers: NU 17H08
STU00207793 ( CTRP (Clinical Trial Reporting Program) )
NU 17H08 ( Other Identifier: Northwestern University )
P30CA060553 ( U.S. NIH Grant/Contract )
NCI-2018-01666 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Posted: October 15, 2018    Key Record Dates
Last Update Posted: December 4, 2018
Last Verified: November 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Rituximab
Nivolumab
Doxorubicin
Liposomal doxorubicin
Prednisone
Vincristine
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Cortisone
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action