Obinutuzumab for CNS Lymphoma

Recruiting at 7 trial locations

Overseen By Holly Rittenberry

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Providence Health & Services

Must be taking: High-dose methotrexate

Must not be taking: Monoclonal antibodies

Disqualifiers: Extra-CNS lymphoma, Active infection, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 2 years

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of obinutuzumab, an immunotherapy drug, in preventing the recurrence or progression of central nervous system lymphoma after initial treatment. The study compares two groups: one receiving obinutuzumab and the other under observation without additional treatment. It seeks participants who have had central nervous system lymphoma, responded well to initial treatment, and are within 75 days of completing it. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it is important to discuss your current medications with the trial team to ensure they do not interfere with the study treatment.

Is there any evidence suggesting that obinutuzumab is likely to be safe for humans?

Research has shown that obinutuzumab is generally well-tolerated as a maintenance treatment for patients with central nervous system lymphoma. Earlier studies reported mild side effects, such as dizziness and flushing, during the first treatment cycle, affecting about 25% of patients. Overall, the treatment was considered safe and effective in controlling cancer. These findings suggest that obinutuzumab offers a promising option for ongoing cancer management with manageable side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for CNS lymphoma?

Obinutuzumab is unique because it targets a protein called CD20 found on the surface of certain lymphoma cells. This mechanism allows it to specifically attack and kill these cancerous cells, potentially offering an advantage over traditional chemotherapy, which targets rapidly dividing cells but can also harm healthy cells. Researchers are excited about obinutuzumab because it might offer a more targeted approach with fewer side effects, improving the quality of life for patients with CNS lymphoma. Unlike the standard of care, which often involves aggressive chemotherapy and radiation, obinutuzumab's targeted action could lead to more effective and less toxic treatment outcomes.

What evidence suggests that obinutuzumab might be an effective treatment for CNS lymphoma?

Research has shown that obinutuzumab might help treat central nervous system lymphoma. In this trial, participants in one arm will receive obinutuzumab, which studies have found can assist the immune system in fighting cancer by stopping cancer cells from growing and spreading. Obinutuzumab attaches to certain proteins on cancer cells, leading to their destruction. Some early results suggest that patients who received this treatment saw their tumors shrink and their condition improve. This indicates that obinutuzumab could be useful as a follow-up treatment for patients who have already responded well to initial therapies. Meanwhile, participants in the other arm will undergo observation for a total of two years. ^{2 3 4 6 7}

Who Is on the Research Team?

Prakash Ambady, MB, MD

Principal Investigator

Providence Health & Services

Are You a Good Fit for This Trial?

This trial is for patients with a type of brain lymphoma who've responded to initial treatment. They must have had high-dose methotrexate-based chemo, be within 75 days post-treatment, and show partial or complete cancer response on an MRI. Participants need decent physical function (KPS >=60), acceptable organ function tests, and agree to use effective contraception.

Inclusion Criteria

Absolute neutrophil count > 1.5 x 10^3 cells/mm^3, +/- 7 days from date of ICF signing

I finished my first cancer treatment less than 75 days ago and it worked.

My lymphoma in the brain was confirmed by tests on my spinal fluid or a biopsy.

Exclusion Criteria

I have non-Hodgkin lymphoma outside of my brain and spinal cord.

History of severe allergic or anaphylactic reactions to monoclonal antibody therapy

I have had another type of cancer that might interfere with this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive obinutuzumab intravenously on days 1 and 2 for the first cycle, and on day 1 for the subsequent cycles. Cycles repeat every 60 days for 2 years in the absence of disease progression or unacceptable toxicity.

2 years

1 visit every 60 days

Observation

Participants undergo observation for a total of 2 years.

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Obinutuzumab

Trial Overview The study is testing if the immunotherapy drug Obinutuzumab helps maintain remission in central nervous system lymphoma after initial success from first-line treatments. It's a phase II trial where some patients will receive this maintenance therapy while others may not.

How Is the Trial Designed?

Group I: Arm I (obinutuzumab Experimental Treatment 3 Interventions

Patients receive obinutuzumab IV on days 1 and 2 for the first cycle, and on day 1 for the subsequent cycles, and on day 1 for the subsequent cycles. Cycles repeat every 60 days for 2 years in the absence of disease progression or unacceptable toxicity.

Group II: Arm II (observation) Active Control 2 Interventions

Patients undergo observation for a total of 2 years.

Who Is Running the Clinical Trial?

Providence Health & Services

Lead Sponsor

Trials

131

Recruited

827,000+

Published Research Related to This Trial

Obinutuzumab, combined with bendamustine, significantly prolonged progression-free survival (PFS) in patients with indolent non-Hodgkin's lymphoma, particularly benefiting those with follicular lymphoma, as shown in the phase III GADOLIN study.

The treatment was generally well-tolerated, with mild to moderate infusion-related reactions being the most common side effects, while neutropenia was the most frequent severe adverse event, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab: A Review in Rituximab-Refractory or -Relapsed Follicular Lymphoma. Dhillon, S.[2018]

Obinutuzumab (GA101) is an effective treatment for non-Hodgkin's lymphoma and is currently undergoing phase 3 clinical trials to further evaluate its efficacy.

A case report of a 62-year-old patient revealed a significant side effect, a widespread lichenoid eruption, highlighting the need for further investigation into the safety profile of GA101.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GA101 (a Novel Anti-CD20 Monoclonal Antibody)-Induced Lichenoid Eruption. Bakkour, W., Coulson, IH.[2022]

Obinutuzumab is an effective treatment for B-cell malignancies, specifically approved in the US for chronic lymphocytic leukaemia (CLL) in combination with chlorambucil, showcasing its efficacy in targeting cancer cells.

Utilizing GlycoMAb® technology, obinutuzumab enhances immune-mediated cell death through increased antibody-dependent cellular cytotoxicity, making it a promising option in ongoing phase III trials for various B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab: first global approval. Cameron, F., McCormack, PL.[2021]

Obinutuzumab, a glycoengineered anti-CD20 monoclonal antibody, shows improved clinical efficacy compared to rituximab in treating non-Hodgkin lymphoma, with a phase I/II study involving patients receiving doses up to 2000 mg.

The study found that a dosing regimen of 1600/800 mg resulted in greater tumor shrinkage without increasing adverse events, leading to the identification of a 1000 mg fixed-dose regimen for further phase III evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale for optimal obinutuzumab/GA101 dosing regimen in B-cell non-Hodgkin lymphoma. Cartron, G., Hourcade-Potelleret, F., Morschhauser, F., et al.[2022]

In preclinical studies involving cynomolgus monkeys, obinutuzumab caused expected B-cell depletion but also led to hypersensitivity reactions, indicating potential safety concerns that were observed at all doses.

Despite these reactions in monkeys, clinical evidence suggests that hypersensitivity to obinutuzumab is rare in humans, highlighting that animal studies may not always predict human responses to immunogenicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypersensitivity Reactions to Obinutuzumab in Cynomolgus Monkeys and Relevance to Humans. Husar, E., Solonets, M., Kuhlmann, O., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06175000?term=AREA%5BBasicSearch%5D(r7159)&rank=1

Maintenance Obinutuzumab in Treating Patients With ... This randomized phase II trial studies how well obinutuzumab works as maintenance treatment in patients with central nervous system lymphoma who have achieved ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06922604

NCT06922604 | Glofitamab With Obinutuzumab Pre- ... Giving glofitamab with obinutuzumab pre-treatment may be safe, tolerable, and/or effective in treating patients with CNS lymphoma. PRIMARY OBJECTIVE: I.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11876112/

New hopes and challenges in targeted therapy and ... This review presents recent advances in the treatment of PCNSL, reviews and discusses the efficacy and challenges of targeted therapy and immunotherapy.

4. trials.braintumor.org trials.braintumor.org/trials/NCT06175000

Maintenance Obinutuzumab in Treating Patients With Central ... This randomized phase II trial studies how well obinutuzumab works as maintenance treatment in patients with central nervous system lymphoma who have achieved ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5737162/

Therapy and outcomes of primary central nervous system ... Estimated overall survival in PCNSL is 37.7% at 3 years and reaches 51.8% in the subgroup treated with multiagent chemotherapy. Abstract. Although the role of ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118730218

Safety Profile of Maintenance Obinutuzumab in Patients ... Background: Although high initial response rates have been reported, fewer than 50% of newly diagnosed primary CNS lymphoma (PCNSL) patients ...

7. researchgate.net researchgate.net/publication/346667017_Safety_Profile_of_Maintenance_Obinutuzumab_in_Patients_with_Primary_CNS_Lymphoma_in_Complete_Response

Safety Profile of Maintenance Obinutuzumab in Patients ... Gr 1 dizziness and flushing during cycle 1 infusion occurred in 3 patients (25%). Conclusions: Maintenance obinutuzumab was well tolerated with an encouraging ...