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

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug combination for CLL patients, using Obinutuzumab and high-dose methylprednisone. It includes patients who are new to treatment and those who haven't responded to other treatments. The goal is to see if this combination can effectively target and destroy cancer cells while reducing inflammation. Obinutuzumab is a fully humanized antibody that targets specific cells and has been approved for use with other treatments in patients with previously untreated CLL.

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.

What data supports the effectiveness of the drug combination Obinutuzumab and high-dose methylprednisolone for treating chronic lymphocytic leukemia?

Research shows that high-dose methylprednisolone can help patients with chronic lymphocytic leukemia who do not respond to other treatments. Additionally, Obinutuzumab, when combined with another drug, has been shown to improve outcomes in patients with previously untreated chronic lymphocytic leukemia. ^{1 2 3 4 5}

Is the combination of Obinutuzumab and HDMP safe for treating chronic lymphocytic leukemia?

Obinutuzumab, when used with other treatments for chronic lymphocytic leukemia, has shown manageable safety with common side effects like infusion-related reactions, neutropenia (low white blood cell count), and infections. High-dose methylprednisolone (HDMP) has been used safely in similar contexts, but specific safety data for the combination of Obinutuzumab and HDMP is not detailed in the available research. ^{2 4 5 6 7}

How is the drug Obinutuzumab + HDMP unique for treating chronic lymphocytic leukemia?

The combination of Obinutuzumab and HDMP (high-dose methylprednisolone) is unique because Obinutuzumab is a glycoengineered antibody that enhances immune cell activity against cancer cells, while HDMP is a steroid that can reduce inflammation and potentially enhance the effectiveness of the antibody. This combination may offer a novel approach by leveraging both immune system activation and anti-inflammatory effects, which is different from standard treatments that typically use chemotherapy or other antibodies alone. ^{3 4 5 8 9}

Research Team

Kipps Thomas, MD

Principal Investigator

University of California, San Diego

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy of high-dose corticosteroid-based treatment for chronic lymphocytic leukemia patients with p53 abnormalities in the era of B-cell receptor inhibitors. [2021]

2. England pubmed.ncbi.nlm.nih.gov

High-dose methylprednisolone can induce remissions in patients with fludarabine-refractory chronic lymphocytic leukaemia. [2013]

3. England pubmed.ncbi.nlm.nih.gov

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

4. United States 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. [2022]

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

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

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

Managing Infusion-Related Reactions for Patients With Chronic Lymphocytic Leukemia Receiving Obinutuzumab. [2017]

7. Italy pubmed.ncbi.nlm.nih.gov

Safety of obinutuzumab alone or combined with chemotherapy for previously untreated or relapsed/refractory chronic lymphocytic leukemia in the phase IIIb GREEN study. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Obinutuzumab (GA101) for the treatment of chronic lymphocytic leukemia and other B-cell non-hodgkin's lymphomas: a glycoengineered type II CD20 antibody. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Obinutuzumab in chronic lymphocytic leukemia. [2015]