ABBV-453 + Obinutuzumab for Chronic Lymphocytic Leukemia

(453 Ph1 CLL Trial)

Not currently recruiting at 23 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AbbVie

Must be taking: Obinutuzumab

Must not be taking: BCL-2 inhibitors

Disqualifiers: Cardiac abnormalities, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a new drug, ABBV-453, in treating chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), particularly for those whose cancer has returned or did not respond to previous treatments. Participants will receive ABBV-453, with some also receiving obinutuzumab (Gazyva) to reduce cancer size before starting ABBV-453. This trial suits those who have tried at least two other treatments for CLL or SLL without success. 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 treatment.

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.

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

Previous studies have tested ABBV-453 to determine its safety as a potential treatment for chronic lymphocytic leukemia (CLL). However, researchers have not yet gathered enough solid information to assess its tolerability. As it remains in early trials, researchers continue to explore its safety.

In contrast, obinutuzumab, used alongside ABBV-453 in this trial, has a well-established safety record, as it is already approved for CLL. Common side effects of obinutuzumab include infusion reactions and low white blood cell counts, which can increase infection risk. In some cases, serious side effects such as significant drops in white blood cell count (neutropenia) and low red blood cell count (anemia) have been reported.

While the safety of obinutuzumab is well-documented, ABBV-453 is still under study to understand its tolerability. Participants in this trial will help researchers gather crucial safety information for ABBV-453. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ABBV-453 in combination with obinutuzumab for treating Chronic Lymphocytic Leukemia (CLL) because it offers a potentially novel approach compared to existing therapies. Unlike current treatments that typically involve chemotherapies or targeted therapies like BTK inhibitors, ABBV-453 is being studied for its unique mechanism as a potential epigenetic modulator. This means it might work by influencing gene expression in cancer cells, which could lead to more effective leukemia control with potentially fewer side effects. Additionally, obinutuzumab is a monoclonal antibody that targets a specific protein on B-cells, complementing ABBV-453's action and possibly enhancing overall treatment efficacy.

What evidence suggests that this trial's treatments could be effective for chronic lymphocytic leukemia?

Research has shown that ABBV-453 is a promising new treatment for chronic lymphocytic leukemia (CLL). Lab studies have demonstrated ABBV-453's strong potential to stop cancer cells from growing. In this trial, participants will receive ABBV-453 combined with obinutuzumab, a drug proven effective in helping CLL patients live longer without disease progression. Previous trials found that obinutuzumab led to higher remission rates compared to some other treatments. These findings suggest that combining ABBV-453 with obinutuzumab might effectively treat CLL. ^{1 6 7 8 9}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• ABBV-453
• Obinutuzumab

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.

How Is the Trial Designed?

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

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]

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, 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, 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]

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 novel humanized anti-CD20 antibody, has been shown to significantly improve overall survival when combined with chlorambucil in untreated comorbid patients with chronic lymphocytic leukemia (CLL).

This antibody enhances antibody-dependent cellular cytotoxicity and directly induces cell death more effectively than previous type I antibodies, marking a significant advancement in CLL treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06291220

A Study Assessing Adverse Event and How Oral ABBV-453 ... 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).

2. abbvieclinicaltrials.com abbvieclinicaltrials.com/study/?id=M24-291

A Study Assessing Adverse Event and How Oral ABBV-453 ... 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).

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11899398/

Real-World Effectiveness of Frontline Treatments Among ... Advances in therapies for patients with chronic lymphocytic leukemia (CLL) have led to prolonged progression-free survival as evidenced by ...

4. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper205998.html

Abbv-453: A Highly Potent and Selective Next Generation ... ABBV-453 has the potential to be the best-in-class next-generation BCL-2 inhibitor and is actively being investigated in phase 1 clinical trials ...

5. researchgate.net researchgate.net/publication/386474175_Abbv-453_A_Highly_Potent_and_Selective_Next_Generation_Small_Molecule_Inhibitor_of_BCL-2

Abbv-453: A Highly Potent and Selective Next Generation ... In vivo studies of ALL demonstrated that at equivalent doses and schedules, ABBV-453 as a monotherapy was significantly more effective in ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124077243

Abbv-453: A Highly Potent and Selective Next Generation ... ABBV-453 has the potential to be the best-in-class next-generation BCL-2 inhibitor and is actively being investigated in phase 1 clinical trials ...

7. stage.abbviescience.com stage.abbviescience.com/en/cancer-types/chronic-lymphocytic-leukemia.html

Chronic Lymphocytic Leukemia (CLL) An estimated 18,740 people in the US were diagnosed during 2023, and 4,490 people died from the disease. Five-year survival rate is 88.0% in the US. CLL is ...

8. synapse.patsnap.com synapse.patsnap.com/drug/7c5d1bd1f14b4caea0025acdd691b682

ABBV-453 - Drug Targets, Indications, Patents A Phase 1/2, Open-Label, Platform Study to Evaluate Safety and Efficacy of the BCL-2 Inhibitor ABBV-453 Given as Monotherapy or in Combination With ...

9. abbviepro.com abbviepro.com/gu/en/Home/Oncology/Tumor-Types/Hematologic-Malignancies-Chronic-Lymphocytic-Leukemia-CLL.html

Chronic Lymphocytic Leukemia (CLL) OVERVIEW. CLL is a slow-progressing cancer in which mature clonal B lymphocytes accumulate in the bone marrow, blood, and other lymphoid tissues.