~7 spots leftby Apr 2026

Venetoclax + Obinutuzumab +/- Acalabrutinib for Chronic Lymphocytic Leukemia

Recruiting in Palo Alto (17 mi)
+2 other locations
Member Detail - DF/HCC
Overseen byJacob D. Soumerai, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Massachusetts General Hospital
No Placebo Group
Prior Safety Data
Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This research study is studying a combination of drugs as a possible treatment for chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The names of the study drugs involved in this study are: * obinutuzumab * venetoclax * acalabrutinib

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot take strong inhibitors or inducers of CYP3A, CYP2C8, CYP2C9, and CYP2C19 within 7 days before starting the study drugs. Also, avoid grapefruit, Seville oranges, and star fruit within 3 days before starting. If you're on dual antiplatelet therapy or warfarin, you cannot participate.

What data supports the idea that Venetoclax + Obinutuzumab +/- Acalabrutinib for Chronic Lymphocytic Leukemia is an effective drug?

The available research shows that the combination of Venetoclax and Obinutuzumab is effective for treating Chronic Lymphocytic Leukemia. In a study comparing this combination to another treatment (Chlorambucil plus Obinutuzumab), patients who received Venetoclax and Obinutuzumab had longer periods without the disease getting worse. They also had higher rates of the disease being undetectable and better overall responses. Another study found that adding Acalabrutinib to Venetoclax and Obinutuzumab could lead to even deeper and longer-lasting remissions. These findings suggest that Venetoclax and Obinutuzumab, with or without Acalabrutinib, are effective options for treating this type of leukemia.12345

What safety data is available for the treatment of Venetoclax, Obinutuzumab, and Acalabrutinib in CLL?

The combination of Venetoclax and Obinutuzumab has been studied in the CLL14 trial, showing an acceptable tolerability profile with notable adverse events like grade 3 or 4 neutropenia, which can be managed with supportive therapy and dose modifications. The incidence of grade 3-4 neutropenia was reported between 52.8%-57.7%. Acalabrutinib, when added to Venetoclax and Obinutuzumab, is being evaluated for its potential to induce deep and durable remissions in CLL patients, but specific safety data for this triplet combination is not detailed in the provided studies.12346

Is the drug combination of Acalabrutinib, Obinutuzumab, and Venetoclax promising for treating Chronic Lymphocytic Leukemia?

Yes, the drug combination of Acalabrutinib, Obinutuzumab, and Venetoclax is promising for treating Chronic Lymphocytic Leukemia. Venetoclax and Obinutuzumab have shown to be effective in improving progression-free survival and response rates compared to traditional chemotherapy. This combination offers a chemotherapy-free option, which is beneficial for patients who cannot tolerate intensive treatments.12467

Research Team

Member Detail - DF/HCC

Jacob D. Soumerai, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

Adults over 18 with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who need treatment and have previously received systemic therapy. They must be in good enough health, not pregnant, agree to contraception, and not have certain heart conditions or other serious illnesses that could interfere with the study.

Inclusion Criteria

I am over 18 years old.
I have been diagnosed with CLL or SLL.
For females of childbearing potential, a negative serum pregnancy test within 7 days of study treatment
See 15 more

Exclusion Criteria

My CLL has transformed into an aggressive form of lymphoma.
I have not had a brain hemorrhage or stroke in the last 6 months.
I do not have any current infections or recent major infections that required IV antibiotics or hospitalization.
See 20 more

Treatment Details

Interventions

  • Acalabrutinib (Bruton's Tyrosine Kinase (BTK) Inhibitor)
  • Obinutuzumab (Monoclonal Antibodies)
  • Venetoclax (B-cell lymphoma-2 (BCL-2) inhibitor)
Trial OverviewThe trial is testing a combination of drugs: obinutuzumab, venetoclax, and possibly acalabrutinib. It aims to find out if these drugs can effectively treat CLL/SLL when given together compared to current standard treatments.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Venetoclax-Obinutuzumab +/- AcalabrutinibExperimental Treatment3 Interventions
A treatment cycle is defined as 28 consecutive days. Participants with undetectable MRD (uMRD) at 1 year will complete an additional 1 year of VO then stop therapy. Participants with high detectable MRD at 1 year will complete an additional 1 year of VO plus acalabrutinib then stop therapy. Participants with low detectable MRD at 1 year will complete an additional 1 year of VO alone. If this eradicates MRD, they will stop therapy. If there is still residual MRD, they will complete an additional 1 year of IVO then stop therapy. If progression occurs on VO, I will be added and IV will be administered indefinitely. After 2 years, V may be stopped and I continued as monotherapy at investigator discretion. * Infused Study Drug: Obinutuzumab on Days 1, 2, 8, and 15 of Cycle 1 and then on Day 1 of Cycles 1-6 * Oral Study Drugs: Venetoclax daily starting on Cycle 1 Day 22 * Oral Drug: acalabrutinib daily for Days 1-28 (if applicable)

Find a Clinic Near You

Research Locations NearbySelect from list below to view details:
Beth Israel Deaconess Medical CenterBoston, MA
Dana-Farber Cancer InstituteBoston, MA
Massachusetts General Hospital Cancer CenterBoston, MA
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Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials
3066
Patients Recruited
13,430,000+

Genentech, Inc.

Industry Sponsor

Trials
1578
Patients Recruited
569,000+

Findings from Research

Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase 3 trial.Al-Sawaf, O., Zhang, C., Tandon, M., et al.[2020]
Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia.Blair, HA.[2021]
Acalabrutinib, venetoclax, and obinutuzumab as frontline treatment for chronic lymphocytic leukaemia: a single-arm, open-label, phase 2 study.Davids, MS., Lampson, BL., Tyekucheva, S., et al.[2021]
Venetoclax consolidation after fixed-duration venetoclax plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (HOVON 139/GiVe): primary endpoint analysis of a multicentre, open-label, randomised, parallel-group, phase 2 trial.Kersting, S., Dubois, J., Nasserinejad, K., et al.[2022]
Venetoclax: A Review in Relapsed/Refractory Chronic Lymphocytic Leukemia.Scott, LJ.[2020]
Evaluation and associated risk factors for neutropenia with venetoclax and obinutuzumab in the treatment of chronic lymphocytic leukemia.Samuels, C., Abbott, D., Niemiec, S., et al.[2022]
An update of venetoclax and obinutuzumab in chronic lymphocytic leukemia.Salvaris, R., Opat, S.[2021]

References

Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase 3 trial. [2020]
Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. [2021]
Acalabrutinib, venetoclax, and obinutuzumab as frontline treatment for chronic lymphocytic leukaemia: a single-arm, open-label, phase 2 study. [2021]
Venetoclax consolidation after fixed-duration venetoclax plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (HOVON 139/GiVe): primary endpoint analysis of a multicentre, open-label, randomised, parallel-group, phase 2 trial. [2022]
Venetoclax: A Review in Relapsed/Refractory Chronic Lymphocytic Leukemia. [2020]
Evaluation and associated risk factors for neutropenia with venetoclax and obinutuzumab in the treatment of chronic lymphocytic leukemia. [2022]
An update of venetoclax and obinutuzumab in chronic lymphocytic leukemia. [2021]