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A study to understand the optimization of the cytokine release syndrome profile for glofitamab along with gemcitabine plus oxaliplatin in patients with relapsed/refractory diffuse large B-cell lymphoma
A Study to Evaluate the Optimization of the Cytokine Release Syndrome Profile for Glofitamab in Combination With Gemcitabine Plus Oxaliplatin in Participants With Relapsed/Refractory Diffuse Large B-Cell Lymphoma
- Cancer
- Non Hodgkin Lymphoma (NHL)
Please note that the recruitment status of the study at your site may differ from the overall study status because some study sites may recruit earlier than others.
Study Status:
Recruiting
This study runs in
Countries
- Korea, Republic of
- United States
Study Identifier:
NCT06806033 2024-516791-15-00 GO45434
Study Summary
The main goal of this trial is to study the frequency and severity of cytokine release syndrome (CRS) in participants with diffuse large B-cell lymphoma (DLBCL) who are using a combination of glofitamab + gemcitabine + oxaliplatin (Glofit-GemOx) followed by glofitamab-only treatment.
Hoffmann-La Roche
Sponsor
Phase 2
Phase
NCT06806033, GO45434, 2024-516791-15-00
Study Identifier
All
Gender
≥18 Years
Age
No
Healthy Volunteers
1. Why is this study needed?
Diffuse large B-cell lymphoma (DLBCL) is the most common type of blood cancer that affects the disease-fighting white blood cells (B-cell). It starts in the lymphatic system, a part of the body's defence system (immune system), and often spreads to other organs. Sometimes, DLBCL may come back after initially responding to treatment (relapsed) or may not respond to the treatment at all (refractory). Therefore, there is always a need to find new treatments.
This study is testing a medicine called glofitamab in combination with 2 other cancer medicines called gemcitabine and oxaliplatin (referred to as GemOx). This combination is being developed as a treatment for relapsed or refractory DLBCL. In this study, the combination of glofitamab with GemOx (Glofit-GemOx) is considered experimental. This means health authorities (like the U.S. Food and Drug Administration and European Medicines Agency) have not approved this combination to treat relapsed or refractory DLBCL. Previous studies have shown that glofitamab can cause an unwanted effect called cytokine release syndrome (CRS). It occurs when the immune system reacts in an unusual way to an infection or cancer therapy. During this reaction, proteins called cytokines are released into the blood, causing symptoms like low blood pressure, rash, fever, chills, difficulty breathing, rapid heartbeat, nausea, and kidney damage.
This study aims to determine how often participants with relapsed or refractory DLBCL experience cytokine release syndrome after being treated with glofitamab in combination with GemOx.
2. Who can take part in the study?
People who are at least 18 years old with a diagnosis of relapsed or refractory DLBCL can take part in this study. People cannot take part in this study if they have other types of cancer or did not respond to only 1 prior treatment for DLBCL. Women who are pregnant or breastfeeding cannot participate in the study.
3. How does this study work?
People will be screened to check if they can participate in the study. The screening period will take place about 28 days before the start of treatment.
Everyone who joins this study will receive Glofit-GemOx as a drip into the vein (infusion) once every 3 weeks for 8 treatment cycles, followed by glofitamab alone for 4 treatment cycles. A treatment cycle is the period of treatment and recovery time before the next set of treatments is given. Participants will receive a single dose of obinutuzumab 7 days before the first dose of glofitamab to reduce the risk of CRS. Participants will also receive a steroid medicine to manage CRS in all the treatment cycles. They may also receive tocilizumab if the CRS event worsens.
This is an open-label study. This means everyone involved, including the participant and the study doctor, will know the study treatment the participant has been given.
During this study, the study doctor will meet the participants approximately 22 times over 40 weeks to check how well the treatment is working and any unwanted effects participants may have. Participants will have follow-up visits every 3 months after completing the study treatment, during which the study doctor will check on the participant’s well-being. Total time of participation in the study will be about 5 years, depending on how the cancer responds to treatment. Participants have the right to stop study treatment and leave the study at any time if they wish to do so.
4. What are the main results measured in this study?
The main result of the study is to find out the number of participants with cytokine-release syndrome (CRS) and the severity of CRS in these participants.
Other key results that will be measured in the study include:
- Number of participants with serious CRS events
- Number of CRS events at start of glofitamab treatment in Cycle 1 compared to events in other cycles
- How CRS is managed and the outcome for participants who experience CRS event
- Number of participants with unwanted effects and the severity of unwanted effects
- Number of participants who are cancer-free or had at least a 30% decrease in the tumour size
- Time taken for the cancer to come back in a participant who was previously cancer free after undergoing treatment
- Time from the start of treatment until the first incidence of cancer worsening, or participants dying due to any cause
5. Are there any risks or benefits in taking part in this study?
Taking part in the study may or may not make participants feel better. But the information collected in the study can help other people with similar health conditions in the future. It may not be fully known at the time of the study how safe and well the study treatment works. The study involves some risks to the participant. But these risks are generally not greater than those related to routine medical care or the natural progression of the health condition. People interested in taking part will be informed about the risks and benefits, as well as any additional procedures or tests they may need to undergo. All details of the study will be described in an informed consent document. This includes information about possible effects and other options of treatment.
Risks associated with the study drugs
Participants may have unwanted effects of the drugs used in this study. These unwanted effects can be mild to severe, even life-threatening, and vary from person to person. During this study, participants will have regular check-ups to see if there are any unwanted effects. Participants will be told about the known unwanted effects of glofitamab and obinutuzumab and possible unwanted effects based on human and laboratory studies or knowledge of similar medicines.
Glofitamab
Known unwanted effects include CRS event-related symptoms and a low number of neutrophils, which is a type of white blood cell that helps the body fight infections (neutropenia).
Obinutuzumab
Known unwanted effects include low numbers of neutrophils (neutropenia), decrease in red blood cells (anemia), difficulty passing stools (constipation), difficulty falling asleep (insomnia), infections, and cough.
Glofitamab and obinutuzumab, are given as a drip into a vein. Known unwanted effects with infusion include irritation where the injection is given, fever, chills, rash, redness, swelling, itching, or pain.
The study medicines may be harmful to an unborn baby. Women and men must take precautions to avoid exposing an unborn baby to the study treatment.
Study Summary
The main goal of this trial is to study the frequency and severity of cytokine release syndrome (CRS) in participants with diffuse large B-cell lymphoma (DLBCL) who are using a combination of glofitamab + gemcitabine + oxaliplatin (Glofit-GemOx) followed by glofitamab-only treatment.
Hoffmann-La Roche
Sponsor
Phase 2
Phase
NCT06806033, GO45434, 2024-516791-15-00
Study Identifier
Obinutuzumab, Glofitamab, Gemcitabine, Oxaliplatin
Treatments
Diffuse Large B-Cell Lymphoma
Condition
Official Title
A Phase II, Open-Label, Multicenter Study to Evaluate the Optimization of the Cytokine Release Syndrome Profile for Glofitamab in Combination With Gemcitabine Plus Oxaliplatin in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Eligibility Criteria
All
Gender
≥18 Years
Age
No
Healthy Volunteers
Inclusion Criteria
- Histologically confirmed DLBCL, not otherwise specified (NOS)
- R/R disease, defined as: relapsed = disease that has recurred following a response that lasted >/= 6 months after completion of the last line of therapy; refractory = disease that did not respond to or that progressed < 6 months after completion of the last line of therapy
- At least one line of prior systemic therapy
- Participants who have failed only one prior line of therapy must not be a candidate for high-dose chemotherapy followed by autologous stem cell transplant (ASCT)
- At least one bi-dimensionally measurable (> 1.5 cm) nodal lesion, or one bi-dimensionally measurable (> 1 cm) extranodal lesion, as measured on CT scan
- Eastern Cooperative Oncology Group (ECOG) status of 0, 1, or 2
- Adequate hematologic and renal function
Exclusion Criteria
- Prior enrollment in Study GO41943 (NCT04313608), GO41944 (STARGLO; NCT04408638), or Study GO44900 (NCT06624085)
- Participant has failed only one prior line of therapy and is a candidate for stem cell transplantation
- History of transformation of indolent disease to DLBCL
- High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, and high-grade B-cell lymphoma NOS, as defined by 2016 WHO guidelines
- Primary mediastinal B-cell lymphoma
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products
- Contraindication to obinutuzumab, gemcitabine or oxaliplatin, or tocilizumab
- Prior treatment with glofitamab or other bispecific antibodies targeting both CD20 and CD3
- Prior treatment with gemcitabine or oxaliplatin
- Peripheral neuropathy or paresthesia assessed to be Grade >/= 2 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 at enrollment
- Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to first study treatment
- Treatment with monoclonal antibodies for the purposes of treating cancer within 4 weeks prior to first study treatment
- Primary or secondary CNS lymphoma at the time of recruitment or history of central nervous system (CNS) lymphoma
- Prior CNS involvement that has been definitively treated and confirmed via magnetic resonance imaging (MRI) or cerebrospinal fluid analysis to be in complete remission is permissible
- Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
- History of other primary malignancy, with exceptions defined by the protocol
- Significant or extensive cardiovascular disease
- Significant pulmonary disease (including moderate or severe obstructive pulmonary disease)
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection (as evaluated by the investigator) within 4 weeks prior to the first study treatment
- Positive for: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); tuberculosis; hepatitis B virus (HBV); hepatitis C virus (HCV); chronic active Epstein-Barr viral infection
- Known or suspected history of hemophagocytic lymphohistiocytosis (HLH) or progressive multifocal leukoencephalopathy
- Adverse events from prior anti-cancer therapy that have not resolved to Grade 1 or better (with the exception of alopecia and anorexia)
- Administration of a live, attenuated vaccine within 4 weeks before first study treatment administration or anticipation that such a live, attenuated vaccine will be required during the study
- Prior solid organ transplantation or prior allogenic stem cell transplant
- Active autoimmune disease requiring treatment
- Prior treatment with systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor agents), within 4 weeks prior to first dose of study treatment
- Ongoing systemic corticosteroid use which, in the opinion of the investigator, puts the participant at increased risk of steroid-related iatrogenic adrenal insufficiency
- Recent major surgery (within 4 weeks before the first study treatment) other than for diagnosis
- Clinically significant history of cirrhotic liver disease
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the participant at high-risk from treatment complications
- Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 18 months after the final dose of study treatment
For the latest version of this information please go to www.forpatients.roche.com