Obinutuzumab + HDMP for Chronic Lymphocytic Leukemia

(GA101 & HDMP Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of California, San Diego

Must not be taking: Chemotherapy, Monoclonal antibodies

Disqualifiers: Pregnancy, Cardiac disease, Pulmonary disease, Infections, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment combination for people with chronic lymphocytic leukemia (CLL). The researchers seek to determine if the drugs Obinutuzumab (Gazyva) and Methylprednisolone (a corticosteroid) work well together and are safe, potentially offering better results than previous treatments. People diagnosed with CLL who need treatment and have had issues with other therapies might be a good fit. Participants will receive the treatments through IV infusions over several cycles. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications, but you cannot have had chemotherapy, monoclonal antibodies, or biological agents within 28 days before starting the study. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that obinutuzumab, when combined with methylprednisolone, is generally well-tolerated by people with chronic lymphocytic leukemia (CLL). In past studies, many patients with CLL received obinutuzumab. Common side effects include low white blood cell counts and infusion reactions, but these are usually manageable.

Methylprednisolone, a type of steroid often used in treatments, can cause side effects like increased blood sugar and mood changes, but these are known and typically controllable. Studies have examined the combined use of these two drugs and found them safe enough for more advanced testing phases, indicating no unexpected safety risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of obinutuzumab and high-dose methylprednisolone (HDMP) for treating Chronic Lymphocytic Leukemia (CLL) because it offers a novel approach compared to current therapies like chemoimmunotherapy or targeted drugs. Obinutuzumab is a monoclonal antibody that targets CD20 on the surface of B cells, leading to their destruction. This mechanism is distinct from traditional chemotherapy, which often affects both healthy and cancerous cells. Additionally, the high-dose methylprednisolone component can help enhance the immune response and reduce inflammation, potentially making this combination more effective in rapidly controlling the disease. This dual-action strategy could provide a more targeted and potentially more effective treatment option for CLL patients.

What evidence suggests that Obinutuzumab + HDMP might be an effective treatment for Chronic Lymphocytic Leukemia?

This trial will evaluate the combination of Obinutuzumab with high-dose methylprednisolone (HDMP) for treating chronic lymphocytic leukemia (CLL). Research has shown that Obinutuzumab targets B-cells, which are often involved in CLL. Studies have found that HDMP alone has helped patients with CLL who do not respond to other treatments. By combining these two treatments, the trial aims to improve response rates compared to using HDMP with other drugs. Early results suggest that this combination might outperform previous therapies. ^{1 6 7 8 9}

Who Is on the Research Team?

Kipps Thomas, MD

Principal Investigator

University of California, San Diego

Are You a Good Fit for This Trial?

This trial is for adults with Chronic Lymphocytic Leukemia who have a life expectancy of at least 6 months, can perform daily activities (ECOG <2), and have adequate kidney, liver, and blood function. It's open to those new to treatment or with previous treatments but not to pregnant women or those on recent other cancer therapies.

Inclusion Criteria

Effective contraception required for women of childbearing potential and men

Indication for treatment as defined by the IWCLL Guidelines (Hallek et al., 2008b)

Anticipated survival of at least 6 months

Exclusion Criteria

History of severe allergic reactions to monoclonal antibody therapy

I have had major surgery recently.

Pregnant or nursing women

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive GA101 - Obinutuzumab and high-dose methylprednisolone (HDMP) by IV infusion for up to 6 cycles (28-day cycles).

24 weeks

Multiple visits for IV infusions during each cycle

Dose-limiting Toxicity Evaluation

Evaluation of dose-limiting toxicities during the first month of therapy as part of phase Ib.

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Methylprednisolone
• Obinutuzumab

Trial Overview The study tests Obinutuzumab combined with high-dose Methylprednisolone in CLL patients. The hypothesis suggests this combination could be more effective than previous similar treatments. Participants will receive these drugs and their responses will be monitored.

How Is the Trial Designed?

Group I: GA101/HDMP Experimental Treatment 1 Intervention

All subjects will receive GA101 - Obinutuzumab by IV infusion for up to 6 cycles (28-day cycles) as follow: * On Cycle 1, Day 1, 100 mg GA101-obinutuzumab will be administered. * On Cycle 1, Day 2, 900 mg of GA101-obinutuzumab will be administered. * On Cycle 1, Days 8 and 15, 1,000 mg of GA101-obinutuzumab will be administered. * On Cycles 2-6, Day 1, 1,000 mg of GA101-obinutuzumab will be administered. All subjects will receive HDMP by IV infusion for up to 4 cycles (28-day cycles) as follow: •On Cycle 1-4, Days 1 to 3, 1,000 mg/m2 Methylprednisolone will be administered.

Methylprednisolone is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Medrol for:

• Allergic reactions
• Blood disorders
• Cancer
• Eye diseases
• Immune system disorders
• Inflammatory diseases
• Respiratory diseases
• Skin diseases

Approved in European Union as Depo-Medrol for:

• Allergic reactions
• Blood disorders
• Cancer
• Eye diseases
• Immune system disorders
• Inflammatory diseases
• Respiratory diseases
• Skin diseases

Approved in Canada as Solu-Medrol for:

• Allergic reactions
• Blood disorders
• Cancer
• Eye diseases
• Immune system disorders
• Inflammatory diseases
• Respiratory diseases
• Skin diseases

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

Obinutuzumab is a newly approved monoclonal antibody for treating chronic lymphocytic leukemia (CLL) in combination with chlorambucil, showing improved efficacy compared to the older drug rituximab.

In a phase III study, patients treated with obinutuzumab plus chlorambucil experienced deeper and longer remissions, with better progression-free survival and higher rates of complete and molecular responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab for chronic lymphocytic leukemia: promise of the first treatment approved with breakthrough therapy designation. Kakkar, AK., Balakrishnan, S.[2015]

In a multinational phase III study, obinutuzumab combined with chlorambucil significantly improved progression-free survival and event-free survival in adults with previously untreated chronic lymphocytic leukaemia (CLL) compared to chlorambucil alone and rituximab plus chlorambucil.

Obinutuzumab plus chlorambucil had a manageable safety profile, with neutropenia and infusion-related reactions being the most common serious side effects, primarily occurring during the first infusion and generally manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab: a review of its use in patients with chronic lymphocytic leukaemia. Hoy, SM.[2018]

Obinutuzumab, in combination with chlorambucil, significantly improved progression-free survival (PFS) in patients with previously untreated chronic lymphocytic leukemia (CLL), with a median PFS of 23.0 months compared to 11.1 months for chlorambucil alone.

The treatment also resulted in a higher overall response rate (ORR) of 75.9% for the obinutuzumab group versus 32.1% for the chlorambucil group, indicating its efficacy in treating CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and drug administration approval: obinutuzumab in combination with chlorambucil for the treatment of previously untreated chronic lymphocytic leukemia. Lee, HZ., Miller, BW., Kwitkowski, VE., et al.[2022]

Obinutuzumab combined with chlorambucil shows better treatment outcomes for patients with untreated chronic lymphocytic leukemia compared to rituximab plus chlorambucil, while maintaining a similar safety profile.

Infusion-related reactions (IRRs) are more common with obinutuzumab, particularly during the first infusion, but these reactions are generally manageable with proper monitoring and management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing Infusion-Related Reactions for Patients With Chronic Lymphocytic Leukemia Receiving Obinutuzumab. Dawson, K., Moran, M., Guindon, K., et al.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9775482/

Obinutuzumab, High-Dose Methylprednisolone (HDMP ... Simple Summary. Patients with chronic lymphocytic leukemia who develop Richter's Syndrome have a poor prognosis. Traditional chemo-immunotherapy ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S000649711932052X

A Phase Ib/II Study of Combined Obinutuzumab (Gazyva) ... High-dose methylprednisolone (HDMP) and rituximab (R) is an effective non-myelosuppressive treatment regimen for patients (pts) with chronic ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6166403/

Obinutuzumab for the Treatment of Chronic Lymphocytic ... The novel mechanism of action of obinutuzumab is associated with significant efficacy in CLL and other B-cell LPDs. Ongoing clinical trials are expected to ...

4. withpower.com withpower.com/trial/phase-2-leukemia-lymphoid-8-2014-bab84

Obinutuzumab + HDMP for Chronic Lymphocytic Leukemia Research shows that high-dose methylprednisolone can help patients with chronic lymphocytic leukemia who do not respond to other treatments. Additionally, ...

5. epistemonikos.org epistemonikos.org/es/documents/c4b8a212164463bb8db4b2e5188dbc928be53e85

a Phase Ib/II Study We hypothesized that HDMP+G would be a highly effective treatment for pts with CLL. To examine the safety and activity of this regimen, we ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2025/125486s037s038lbl.pdf

GAZYVA® (obinutuzumab) injection, for intravenous use The data below are based on a safety population of 773 previously untreated patients with CLL in the CLL11 study. Patients were treated with chlorambucil alone, ...

7. gazyva-hcp.com gazyva-hcp.com/cll/side-effects-and-safety/premedicating-for-irr.html

GAZYVA® (obinutuzumab) Premedication for First-Line CLL Additional Important Safety Information. Previously Untreated CLL. The most common Grade 3 to 4 adverse reactions (incidence ≥10%) observed in patients with CLL ...

8. researchgate.net researchgate.net/publication/336418977_A_Phase_IbII_Study_of_Combined_Obinutuzumab_Gazyva_and_High-Dose_Methylprednisolone_HDMP_As_Treatment_for_Patients_with_Chronic_Lymphocytic_Leukemia_CLL

A Phase Ib/II Study of Combined Obinutuzumab (Gazyva) ... Phase III studies have demonstrated that CLL pts treated with chlorambucil and obinutuzumab-Gazyva (G), another anti-CD20 mAb, had a superior ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6278964/

Safety of obinutuzumab alone or combined with ... The safety of obinutuzumab, alone or with chemotherapy, was studied in a non-randomized, open-label, non-comparative, phase IIIb study (GREEN) in previously ...