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AMC 120, Glofitamab Plus Chemoimmunotherapy in Newly Diagnosed HIV-Associated Large B-Cell Lymphoma (The "Glofit-RCHOP Study")

ConditionsAIDS-Related Diffuse Large B-cell LymphomaDiffuse Large B-Cell Lymphoma, Not Otherwise SpecifiedHigh Grade B-Cell Lymphoma With MYC and BCL2 RearrangementsHigh Grade B-Cell Lymphoma, Not Otherwise SpecifiedLugano Classification Stage II Adult Non-Hodgkin Lymphoma AJCC v8Lugano Classification Stage III Adult Non-Hodgkin Lymphoma AJCC v8Lugano Classification Stage IV Adult Non-Hodgkin Lymphoma AJCC v8Plasmablastic LymphomaPrimary Effusion Lymphoma
Trial statusNot yet recruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorNational Cancer Institute (NCI)

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Measurable lymph nodes with longest diameter > 1.5 cm, or

Measurable extranodal lesions with longest diameter > 1.0 cm

Disqualifiers

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

Trial design

Design model

Single group

Treatments tested in this trial

  • Biopsy Procedure

    Procedure/Surgery

    Undergo tumor tissue biopsy

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Bone Marrow Aspiration

    Procedure/Surgery

    Undergo bone marrow biopsy or aspiration

  • Bone Marrow Biopsy

    Procedure/Surgery

    Undergo bone marrow biopsy or aspiration

  • Computed Tomography

    Procedure/Surgery

    Undergo PET/CT

  • Cyclophosphamide

    Drug

    Given IV

  • Doxorubicin Hydrochloride

    Drug

    Given IV

  • Echocardiography Test

    Procedure/Surgery

    Undergo ECHO

  • Glofitamab

    Biological/Vaccine

    Given IV

  • Positron Emission Tomography

    Procedure/Surgery

    Undergo PET/CT

  • Prednisone

    Drug

    Given PO

  • Questionnaire Administration

    Other intervention

    Ancillary studies

  • Rituximab

    Biological/Vaccine

    Given IV

  • Vincristine Sulfate

    Drug

    Given IV

Treatment groups

15 Participants
are divided into 1 treatment group
Group A: Treatment (RCHOP, glofitamab)Experimental treatment 14 interventions

Trial outcomes

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.

Time frame
Up to cycle 4 (Cycles = 21 days)

Secondary outcomes

1

Incidence and severity of adverse events (AEs) and serious AEs

Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome will be graded using the American Society for Transplantation and Cellular Therapy Cytokine Release Syndrome criteria. All reported toxicities, regardless of attribution, by toxicity type and maximum grade will be summarized, and sorted by number of participants experiencing the toxicity. Safety data will be based mainly on the frequency and attribution of AEs, the frequency of discontinuation of treatment due to toxicity during study treatment, and the proportion of participants experiencing grade 3 or higher AEs related to the treatment components. AEs will be summarized by presenting the number and percentage of participants having any AE.

Time frame
Up to 2 years after completion of study treatment
2

Complete response rates (CRR)

Defined as the proportion of participants who achieve complete response (CR) among evaluable participants until end of treatment. CRR will be estimated using proportion and corresponding 95% confidence intervals using the Clopper-Pearson method.

Time frame
Up to 8 cycles (Cycles = 21 days)
3

Overall response rate (ORR)

Defined as the proportion of participants who achieve CR or partial response among evaluable participants. ORR will be estimated using proportion and corresponding 95% confidence intervals using the Clopper-Pearson method.

Time frame
Up to 8 cycles (Cycles = 21 days)
4

Progression-free survival (PFS)

Point estimates (e.g. median and 12 months PFS) with 95% confidence intervals will be calculated using the Kaplan-Meier product limit method to summarize the results. Differences in PFS by groups will be tested using the log-rank test. The association between baseline covariates and PFS will be assessed using a Cox proportional hazards regression model.

Time frame
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

Other outcomes

1

Change in circulating tumor deoxyribonucleic acid

Will be reported using descriptive statistics such as mean, standard deviation, median, interquartile range (IQR), and range for continuous variables and counts and percentages for categorical variables. Group comparison will be done using a Student's t-test and/or Mann-Whitney U test for two groups and Analysis of Variance (ANOVA) and/or Kruskal-Wallis test for comparing more than two groups. Biomarkers measured multiple times will be analyzed using the change from the baseline (CFB). Linear regression model, logistic regression model, Cox proportional hazard regression model, Pearson's correlation coefficients, and Spearman's correlation coefficients will be used to examine the association between exploratory endpoints and other endpoints.

Time frame
From baseline up to cycle 7 (Cycles = 21 days)
2

Genetic subtypes of HIV-associated large B-cell lymphoma

Will be reported using descriptive statistics such as mean, standard deviation, median, IQR, and range for continuous variables and counts and percentages for categorical variables. Group comparison will be done using a Student's t-test and/or Mann-Whitney U test for two groups and ANOVA and/or Kruskal-Wallis test for comparing more than two groups. Biomarkers measured multiple times will be analyzed using the CFB. Linear regression model, logistic regression model, Cox proportional hazard regression model, Pearson's correlation coefficients, and Spearman's correlation coefficients will be used to examine the association between exploratory endpoints and other endpoints.

Time frame
Up to 2 years after completion of study treatment
3

Change in CD4 and CD8

Will be reported using descriptive statistics such as mean, standard deviation, median, IQR, and range for continuous variables and counts and percentages for categorical variables. Group comparison will be done using a Student's t-test and/or Mann-Whitney U test for two groups and ANOVA and/or Kruskal-Wallis test for comparing more than two groups. Biomarkers measured multiple times will be analyzed using the CFB. Linear regression model, logistic regression model, Cox proportional hazard regression model, Pearson's correlation coefficients, and Spearman's correlation coefficients will be used to examine the association between exploratory endpoints and other endpoints.

Time frame
From baseline up to 12 months after completion of R-CHOP
4

T-cell subsets, serum levels of cytokines, and inflammation-associated/microbial-translocation molecular profiles

Will be reported using descriptive statistics such as mean, standard deviation, median, IQR, and range for continuous variables and counts and percentages for categorical variables. Group comparison will be done using a Student's t-test and/or Mann-Whitney U test for two groups and ANOVA and/or Kruskal-Wallis test for comparing more than two groups. Biomarkers measured multiple times will be analyzed using the CFB. Linear regression model, logistic regression model, Cox proportional hazard regression model, Pearson's correlation coefficients, and Spearman's correlation coefficients will be used to examine the association between exploratory endpoints and other endpoints.

Time frame
Up to 2 years after completion of study treatment

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

National Cancer Institute (NCI)

Lead sponsor

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: