ABBV-453 + Obinutuzumab for Chronic Lymphocytic Leukemia

(453 Ph1 CLL Trial)

Recruiting in Palo Alto (17 mi)

+18 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: AbbVie

Must be taking: Obinutuzumab

Must not be taking: BCL-2 inhibitors

Disqualifiers: Cardiac abnormalities, HIV, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries. The purpose of this study is to assess how well ABBV-453 works adult participants with relapsed/refractory (R/R) untreated CLL/small lymphocytic lymphoma (SLL). Adverse events, pharmacokinetics, and change in disease activity will be assessed. ABBV-453 is an investigational drug for the treatment of CLL and SLL. There are 2 parts to this study. In part A participants will be placed 1 of 5 cohorts with a specific target dose for each cohort and receive obinutuzumab during the debulking period followed escalating doses of ABBV-453, until the appropriate target dose is achieved. In part B participants will be placed in 2 cohorts and receive up to the maximum dose in part A, with cohort 2.1 including a debulking period (obinutuzumab) as in part A. Approximately 80 adult participants with previously R/R CLL/SLL will be enrolled in the study in approximately 40 sites across the world. Participants in part A will placed into 1 of 5 cohorts with a specific target dose for each cohort and will receive intravenous (IV) obinutuzumab as part of the debulking period, followed by escalating doses of oral ABBV-453 until the appropriate target dose is achieved. Participants in part B will be place in one of 2 cohorts. Participants in cohort 2.1 will receive IV obinutuzumab as part of the debulking period, followed by escalating doses of oral ABBV-453 until the maximum target dose from part A is achieved. Participants in cohort 2.2 will receive no treatment during the the debulking period, followed by escalating doses of oral ABBV-453 until the maximum target dose from part A is achieved. The estimated study duration is 5 years. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, and checking for side effects.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you cannot take certain drugs that affect liver enzymes (CYP3A inhibitors) within 14 days before starting the trial medication.

What data supports the effectiveness of the drug combination ABBV-453 and Obinutuzumab for treating chronic lymphocytic leukemia?

Obinutuzumab, when combined with chlorambucil, has shown significant improvement in progression-free survival for patients with chronic lymphocytic leukemia compared to chlorambucil alone. This suggests that Obinutuzumab is effective in treating this condition, although specific data on ABBV-453 is not provided. ^{1 2 3 4 5}

Is the combination of ABBV-453 and Obinutuzumab safe for humans?

Obinutuzumab, also known as Gazyva, has been used in combination with chlorambucil for treating chronic lymphocytic leukemia and has shown a manageable safety profile. Common side effects include infusion-related reactions, which are usually mild to moderate and can be managed by adjusting the infusion rate. ^{1 2 4 6 7}

What makes the drug ABBV-453 + Obinutuzumab unique for treating chronic lymphocytic leukemia?

The combination of ABBV-453 with Obinutuzumab is unique because Obinutuzumab is a glycoengineered antibody that enhances immune system activity to kill cancer cells more effectively, and ABBV-453 may offer additional benefits, although its specific role in this combination is not detailed in the available research. ^{1 2 3 4 7}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

This trial is for adults with CLL/SLL who have tried at least two cancer treatments and don't have better treatment options. They must meet certain lab value criteria to participate.

Inclusion Criteria

My CLL/SLL has come back or didn't respond after 2 treatments, and there's no better treatment option.

My lab results meet the trial's requirements.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Debulking and Dose Escalation

Participants receive intravenous obinutuzumab during the debulking period followed by escalating doses of oral ABBV-453 until the appropriate target dose is achieved

Up to 18 months

Regular visits at a hospital or clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Regular visits at a hospital or clinic

Treatment Details

Interventions

• ABBV-453 (Other)
• Obinutuzumab (Monoclonal Antibodies)

Trial Overview The study tests ABBV-453, a new drug for CLL/SLL. Participants will receive varying doses after an initial obinutuzumab period, aiming to find the right dose. The study has two parts and involves regular hospital visits over five years.

Participant Groups

Group I: Part B: Cohort 2.2 ABBV-453 Dose E Experimental Treatment 1 Intervention

Participants will no participate in the debulking period and receive escalating doses of ABBV-453, until the dose E is achieved, during the 5 year study duration.

Group II: Part B: Cohort 2.1 ABBV-453 Dose E Experimental Treatment 2 Interventions

Participants will receive obinutuzumab during the debulking period followed escalating doses of ABBV-453, until the dose E is achieved, during the 5 year study duration.

Group III: Part A: Cohort 1.5 ABBV-453 Dose E Experimental Treatment 2 Interventions

Participants will receive obinutuzumab during the debulking period followed escalating doses of ABBV-453, until the dose E is achieved, during the 5 year study duration.

Group IV: Part A: Cohort 1.4 ABBV-453 Dose D Experimental Treatment 2 Interventions

Participants will receive obinutuzumab during the debulking period followed escalating doses of ABBV-453, until the dose D is achieved, during the 5 year study duration.

Group V: Part A: Cohort 1.3 ABBV-453 Dose C Experimental Treatment 2 Interventions

Participants will receive obinutuzumab during the debulking period followed escalating doses of ABBV-453, until the dose C is achieved, during the 5 year study duration.

Group VI: Part A: Cohort 1.2 ABBV-453 Dose B Experimental Treatment 2 Interventions

Participants will receive obinutuzumab during the debulking period followed escalating doses of ABBV-453, until the dose B is achieved, during the 5 year study duration.

Group VII: Part A: Cohort 1.1 ABBV-453 Dose A Experimental Treatment 2 Interventions

Participants will receive obinutuzumab during the debulking period followed escalating doses of ABBV-453, until the dose A is achieved, during the 5 year study duration.

Who Is Running the Clinical Trial?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Findings from Research

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]

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, a new type II fully humanized CD20 antibody, shows promise in treating chronic lymphocytic leukemia (CLL) by inducing greater antibody-dependent cell-mediated cytotoxicity (ADCC) compared to the older antibody rituximab.

Clinical trials have demonstrated that obinutuzumab leads to more effective B-cell depletion in CLL patients, suggesting it may provide more durable responses and potentially improve long-term outcomes in CLL therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab in chronic lymphocytic leukemia: design, development and place in therapy. Al-Sawaf, O., Fischer, K., Engelke, A., et al.[2018]

References

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

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

2. 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]

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

Targeted treatment for chronic lymphocytic leukemia: clinical potential of obinutuzumab. [2020]

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

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

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

Obinutuzumab in chronic lymphocytic leukemia: design, development and place in therapy. [2018]

6. England pubmed.ncbi.nlm.nih.gov

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

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

Obinutuzumab: first global approval. [2021]