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

Trial Summary

What is the purpose of this trial?

This randomized phase II trial studies how well obinutuzumab works as maintenance treatment in patients with central nervous system lymphoma who have achieved the disappearance of all signs of cancer in response to treatment (complete response) or a decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment (partial response). Immunotherapy with obinutuzumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread.

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 Obinutuzumab generally safe for humans?

Obinutuzumab, also known as Gazyva, has been studied for various conditions and generally has a manageable safety profile. Common side effects include mild to moderate infusion-related reactions and low white blood cell counts, while serious allergic reactions are rare in humans. ^{1 2 3 4 5}

Research Team

Prakash Ambady, MB, MD

Principal Investigator

Providence Health & Services

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 (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, 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]

References

1. France pubmed.ncbi.nlm.nih.gov

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

2. New Zealand pubmed.ncbi.nlm.nih.gov

Obinutuzumab: first global approval. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

GA101 (a Novel Anti-CD20 Monoclonal Antibody)-Induced Lichenoid Eruption. [2022]

4. Italy pubmed.ncbi.nlm.nih.gov

Rationale for optimal obinutuzumab/GA101 dosing regimen in B-cell non-Hodgkin lymphoma. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Hypersensitivity Reactions to Obinutuzumab in Cynomolgus Monkeys and Relevance to Humans. [2018]