Testing the Combination of Nivolumab and ASTX727 for Relapsed or Refractory B-Cell Lymphoma
A Phase 1 Study of Nivolumab in Combination With ASTX727 in B-cell Lymphoma (NHL or HL) With an Expansion Cohort in Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) and Hodgkin Lymphoma (HL)
5 other identifiers
interventional
32
1 country
9
Brief Summary
This phase I trial tests the safety, side effects, and best dose of nivolumab in combination with ASTX727 in treating B-cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. ASTX727 consists of the combination of decitabine and cedazuridine. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Giving nivolumab in combination with ASTX727 may shrink and stabilize cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Nov 2022
Longer than P75 for phase_1
9 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 8, 2022
CompletedFirst Posted
Study publicly available on registry
March 9, 2022
CompletedStudy Start
First participant enrolled
November 3, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 28, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 28, 2027
May 5, 2026
March 1, 2026
4.7 years
March 8, 2022
May 2, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Incidence of adverse events
Frequency of subjects experiencing toxicities will be tabulated. Toxicities will be assessed and graded according to Common Terminology Criteria for Adverse Events version 5.0 terminology. Exact 95% confidence intervals around the toxicity proportions will be calculated.
Up to 2 years
Secondary Outcomes (6)
Complete response rate
Up to 2 years
Partial response rate
Up to 2 years
Overall response rate
Up to 2 years
Duration of response
Up to 2 years
Overall survival
Up to 2 years
- +1 more secondary outcomes
Study Arms (1)
Treatment (nivolumab, decitabine and cedazuridine)
EXPERIMENTALPatients receive decitabine and cedazuridine PO QD on days 1-3 or 1-5 of each cycle and nivolumab IV over 30 minutes on day 15 of each cycle. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients with CR, PR, or SD after 12 cycles receive decitabine and cedazuridine for an additional 12 months. Patients also undergo PET/CT and collection of blood samples throughout the trial.
Interventions
Undergo PET/CT
Undergo collection of blood samples
Given PO
Given IV
Undergo PET/CT
Eligibility Criteria
You may qualify if:
- Dose Escalation: Histologically confirmed relapsed or refractory B cell lymphoma (non-Hodgkin lymphoma \[NHL\] or Hodgkin lymphoma \[HL\])
- Dose Expansion: Patients must have histologically confirmed relapsed or refractory DLBCL or HL
- Patients with DLBCL must have failed at least first line chemotherapy and must be transplant ineligible (either secondary to performance status or lack of adequate disease control or patient preference). Patients may be relapsed after autologous or allogeneic stem cell transplant (SCT), or after chimeric antigen receptor (CAR)-T cell therapy
- In dose escalation patients with HL or B cell NHL other than DLBCL must have relapsed after at least 2 lines of therapy and have no other curative options left. HL patients must be brentuximab vedotin refractory or intolerant. In dose expansion, patients with classic HL must have relapsed after at least 2 lines of therapy, and had autologous stem cell transplantation (ASCT), be ineligible for ASCT, or have refused ASCT. Prior treatment with checkpoint inhibitor is allowed
- Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of nivolumab in combination with ASTX727 in patients \< 18 years of age, children are excluded from this study
- Eastern Cooperative Oncology Group (ECOG)/Karnofsky performance status =\< 2 (Karnofsky \>= 70%)
- Leukocytes \>= 1,500/mcL (unless documented bone marrow involvement in which case lower values may be allowed)
- Absolute neutrophil count \>= 1,000/mcL (unless documented bone marrow involvement in which case lower values may be allowed)
- Platelets \>= 75,000/mcL (unless documented bone marrow involvement in which case lower values may be allowed)
- Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional ULN
- Serum creatinine =\< 1.5 x ULN OR creatinine clearance (CrCl) \>= 50 mL/min (if using the Cockcroft-Gault formula)
- Patients with a requirement for steroid treatment or other immunosuppressive treatment: Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
- 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
- +11 more criteria
You may not qualify if:
- Patients who have had chemotherapy or radiotherapy within 4 weeks (2 weeks for Revlimid, 6 weeks for nitrosoureas or mitomycin C) prior to entering the study. Palliative (limited-field) radiation therapy is permitted, if all of the following criteria are met:
- Repeat imaging demonstrates no new sites of bone metastases
- The lesion being considered for palliative radiation is not a target lesion
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
- Patients who have had prior treatment with anti-PD-1/PD-L1 inhibitors or anti CTLA4 antibodies and were permanently discontinued from further treatment because of an adverse event. All other prior therapies are permissible. Prior checkpoint inhibitor therapy is allowed if there was no discontinuation due to adverse event
- Patients who are receiving any other investigational agents
- Patients with known brain metastases or leptomeningeal metastases may be excluded because of poor prognosis and concerns regarding progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ASTX727 or nivolumab, including severe hypersensitivity reaction to any monoclonal antibody
- Patients with uncontrolled intercurrent illness
- Patients with cognitive or other impairment that would prevent compliance with study requirements
- Pregnant women are excluded from this study because ASTX727 is a DNMTi agent and nivolumab is a PD-L1 inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ASTX727 and nivolumab, breastfeeding should be discontinued if the mother is treated with ASTX727 and nivolumab
- Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded. These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome (GBS), myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease. Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
- Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (9)
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233, United States
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
Yale University
New Haven, Connecticut, 06520, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, 60451, United States
University of Chicago Medicine-Orland Park
Orland Park, Illinois, 60462, United States
NYU Langone Hospital - Long Island
Mineola, New York, 11501, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Catherine S Diefenbach
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 8, 2022
First Posted
March 9, 2022
Study Start
November 3, 2022
Primary Completion (Estimated)
June 28, 2027
Study Completion (Estimated)
June 28, 2027
Last Updated
May 5, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
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.