AMC 120, Glofitamab Plus Chemoimmunotherapy in Newly Diagnosed HIV-Associated Large B-Cell Lymphoma (The "Glofit-RCHOP Study")
A Feasibility Study of Glofitamab Plus Chemoimmunotherapy in Newly Diagnosed HIV-Associated Large B-Cell Lymphoma
3 other identifiers
interventional
15
0 countries
N/A
Brief Summary
This phase I trial studies the safety and side effects of glofitamab plus a chemoimmunotherapy regimen called R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in treating patients newly-diagnosed with HIV-associated large B-cell lymphoma. Glofitamab is a bispecific monoclonal antibody, which can bind to two different antigens that are expressed by cancer cells (CD3 and CD20) at the same time. This may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill cancer cells. It may also lower the body's immune response. Doxorubicin is in a class of medications called anthracyclines. Doxorubicin damages the cell's DNA and may kill cancer cells. It also blocks a certain enzyme needed for cell division and DNA repair. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Prednisone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Giving glofitamab in combination with the R-CHOP regimen may be a safe treatment for patients with newly-diagnosed with HIV-associated large B-cell lymphoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Sep 2026
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 13, 2026
CompletedFirst Posted
Study publicly available on registry
June 16, 2026
CompletedStudy Start
First participant enrolled
September 11, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
April 30, 2028
Study Completion
Last participant's last visit for all outcomes
April 30, 2028
July 8, 2026
June 1, 2026
1.6 years
June 13, 2026
July 7, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Ability to deliver at least 4 full cycles of glofitamab-rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (Glofit-RCHOP) (Feasibility)
Feasibility status is defined by the ability to deliver at least 4 cycles of Glofit-RCHOP (i.e. study cycles 1-4). The proportion of the participants who completed at least 4 cycles of Glofit-RCHOP treatment (i.e. cycles 1-4) will be estimated. Will report 95% confidence interval of the above proportion. For the regimen Glofit-RCHOP to be declared feasible, at least 12 out of 15 evaluable participants must complete at least 4 full cycles of Glofit-RCHOP.
Up to cycle 4 (Cycles = 21 days)
Secondary Outcomes (6)
Incidence and severity of adverse events (AEs) and serious AEs
Up to 2 years after completion of study treatment
Complete response rates (CRR)
Up to 8 cycles (Cycles = 21 days)
Overall response rate (ORR)
Up to 8 cycles (Cycles = 21 days)
Progression-free survival (PFS)
From treatment initiation and date of documented progression or date of death from any cause, assessed up to 2 years after completion of study treatment
Overall survival (OS)
From treatment initiation and date of death from any cause, assessed up to 2 years after completion of study treatment
- +1 more secondary outcomes
Other Outcomes (7)
Change in circulating tumor deoxyribonucleic acid
From baseline up to cycle 7 (Cycles = 21 days)
Genetic subtypes of HIV-associated large B-cell lymphoma
Up to 2 years after completion of study treatment
Change in CD4 and CD8
From baseline up to 12 months after completion of R-CHOP
- +4 more other outcomes
Study Arms (1)
Treatment (RCHOP, glofitamab)
EXPERIMENTALPatients receive RCHOP consisting of: rituximab IV over 90-360 minutes, cyclophosphamide IV over 1 hour, doxorubicin IV over 3-10 minutes, and vincristine IV over 3-10 minutes on day 1 of each cycle, and prednisone PO QD on days 1-5 of each cycle. Patients also receive glofitamab IV over 2-8 hours on days 8 and 15 of cycle 2 and on day 8 of cycles thereafter. Cycles of RCHOP repeat every 21 days for 6 cycles, and cycles of glofitamab repeat every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO, bone marrow biopsy or aspiration, PET/CT, and blood sample collection throughout the study. Patients may also undergo tumor tissue biopsy during screening.
Interventions
Undergo tumor tissue biopsy
Undergo blood sample collection
Undergo bone marrow biopsy or aspiration
Undergo bone marrow biopsy or aspiration
Undergo PET/CT
Given IV
Given IV
Given IV
Given IV
Undergo ECHO
Undergo PET/CT
Given PO
Given IV
Eligibility Criteria
You may qualify if:
- Participant is able to understand and willing to sign a written informed consent document
- Participants must have histologically (via at least a core or ideally, incisional or excisional biopsy) documented CD20 positive newly diagnosed HIV-associated LBCL as per World Health Organization (WHO) 5th edition, diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS); high grade B-cell lymphoma-NOS or DLBCL/high grade B-cell lymphoma with MYC and BCL2 rearrangement. Plasmablastic lymphoma and primary effusion lymphoma may be included only if CD20-positive
- Stage II-IV disease (as per Lugano Staging Criteria) that is measurable as defined below:
- Measurable lymph nodes with longest diameter \> 1.5 cm, or
- Measurable extranodal lesions with longest diameter \> 1.0 cm
- Participants with bone marrow involvement only will be eligible as long as the morphological bone marrow involvement is documented on a bone marrow biopsy. These participants, however, will need to be willing to undergo subsequent bone marrow biopsies for response assessment and documentation
- Evidence of HIV infection. Participants must have documentation of HIV-1 infection by means of any one of the following:
- Documentation of HIV diagnosis in the medical record by a licensed health care provider;
- Documentation of receipt of ART (at least two different medications that do not constitute a prescription for pre-exposure prophylaxis) by a licensed health care provider. Documentation may be a record of an ART prescription in the participant's medical record, a written prescription in the name of the participant for ART, or pill bottles for ART with a label showing the participant's name;
- HIV-1 ribonucleic acid (RNA) detection by a licensed HIV-1 RNA assay at any time;
- Any licensed HIV screening antibody and/or HIV antibody/antigen combination assay confirmed by a second licensed HIV assay such as a HIV-1 Western blot confirmation or HIV rapid multispot antibody differentiation assay.
- Note: The term "licensed" refers to a kit that has been certified or licensed by an oversight body within the participating country and validated internally (e.g., United States \[US\] Food and Drug Administration \[FDA\]).
- World Health Organization and Centers for Disease Control and Prevention guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.
- Participants with HIV must be on treatment with effective ART that is in accordance with the current International AIDS Society guidelines concurrently with chemotherapy. Use of experimental antiretroviral agents or those containing zidovudine (including Combivir and Trizivir) or ritonavir (includes Norvir® or Kaletra®), cobicistat, didanosine (Videx® or Videx EC®), or similar potent CYP3 inhibitors are prohibited. In order to be eligible, participants taking zidovudine or ritonavir, cobicistat, didanosine, or other CYP3 inhibitors must change to a different regimen 7 days prior to protocol therapy initiation. Changes to ART therapy during the study may be made if medically necessary (toxicity, failure of regimen, etc.). Participants must be on ART for at least 7 days prior to initiation of protocol therapy except for ART-naïve participants who need to get started on ART within the 1st cycle of study treatment (before cycle 2 day 1). ART needs to be approved by protocol chair or co-chair prior to enrollment
- Age ≥ 18 years. Because no dosing or adverse event (AE) data are currently available on the use of glofitamab in combination with RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in participants \< 18 years of age, children are excluded from this study
- +12 more criteria
You may not qualify if:
- Participants who are receiving any other investigational agents
- Participants with active parenchymal central nervous system (CNS) lymphomatous involvement are excluded; however, asymptomatic leptomeningeal disease is allowed as long as participants have ongoing CNS directed therapy, except during the initial safety-run in phase, during which participants with leptomeningeal disease will also be excluded
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study
- Uncontrolled intercurrent illness including, but not limited to: symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, significant pulmonary disease (including, but not limited to clinically significant obstructive pulmonary disease or history of bronchospasm), clinically significant liver disease (including viral or other hepatitis or cirrhosis) or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements or make participation in this protocol unreasonably hazardous
- Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with the study agent(s), breastfeeding should be discontinued if the mother is treated with the study agent(s). These potential risks may also apply to other agents used in this study
- Participants with refractory HIV disease will not be eligible. Refractory HIV will be defined as prior ART exposure and HIV viral load \> 1000 copies/uL and no options for HIV control evaluated by HIV genotyping. Participants with HIV viral load \> 1000 copies/uL can be enrolled if additional ART will be initiated
- Participants who have had chemotherapy other than allowable pre-trial therapy outlined below, or radiotherapy other than palliative radiation for medical emergencies (i.e., cord compression or impending fracture), within the last four weeks.
- Allowable prior therapy:
- A maximum of one cycle of combination chemotherapy, including CHOP ± rituximab and etoposide-prednisone-Oncovin-cyclophosphamide-hydroxydaunorubicin (EPOCH) ± rituximab. The start of previous chemotherapy cycle must occur at least 21 days but no more than 35 days prior to beginning treatment under this protocol, and this cycle will count towards the maximum of six cycles under this study (i.e., cycle received prior to study enrollment will count as cycle 1) OR
- One prior course of limited therapy including cyclophosphamide and/or glucocorticoids and/or rituximab to improve fitness for combination chemotherapy (i.e., those with impaired hepatic function, renal function and or performance status due to lymphomatous involvement). The start of this therapy may occur up to 35 days prior to beginning treatment under this protocol; cyclophosphamide administration must have been completed at least 14 days prior to initiation of protocol therapy. Such treatment will not count towards the maximum of six cycles under this study (i.e., participants will receive six cycles on study and start with cycle 1 of RCHOP)
- Participants must not have had previous anthracycline treatment within the last two years, except for one cycle off protocol or liposomal doxorubicin. Any prior exposure to liposomal doxorubicin is allowed as long as the left ventricular ejection fraction is ≥ 45%. It is at the discretion of the investigator if prior exposure to doxorubicin more than two years prior is acceptable
- Participants with active tuberculosis and other active opportunistic infections requiring active treatment
- Participants with active fungal infection or history of opportunistic infection requiring continuous prophylaxis or treatment with fluconazole, voriconazole or posaconazole. Oral candidiasis or fungal nail bed infections are permitted
- Participants with chronic hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). All participants will be required to be screened for Hepatitis B. Participants with resolved infection (i.e., participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen \[anti-HBc\] and/or antibodies to hepatitis B surface antigen \[anti-HBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of Hepatitis B virus (HBV) DNA levels. Participants who are PCR positive will be excluded. EXCEPTION: Participants with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR. For participants who have evidence of prior Hepatitis B exposure and are PCR negative, hepatitis B (Hep B) reactivation prophylaxis is mandated using institutional guidelines
- If hepatitis C antibody positive, participants will be excluded from study unless hepatitis C viral load is undetectable. Additionally, participants must have no evidence of cirrhosis and have liver function tests (LFTs)
- +17 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Stefan K Barta
AIDS Malignancy Consortium
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
June 13, 2026
First Posted
June 16, 2026
Study Start (Estimated)
September 11, 2026
Primary Completion (Estimated)
April 30, 2028
Study Completion (Estimated)
April 30, 2028
Last Updated
July 8, 2026
Record last verified: 2026-06
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.