Acalabrutinib, Venetoclax, and Obinutuzumab for Initial Therapy of CLL (AVO)
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|ClinicalTrials.gov Identifier: NCT03580928|
Recruitment Status : Recruiting
First Posted : July 10, 2018
Last Update Posted : December 11, 2018
This research study is evaluating the combination of three drugs - acalabrutinib, venetoclax, and obinutuzumab -- as a possible treatment for chronic lymphocytic leukemia (CLL).
The drugs involved in this study are:
|Condition or disease||Intervention/treatment||Phase|
|Chronic Lymphocytic Leukemia (CLL)||Drug: Venetoclax Drug: Obinutuzumab Drug: Acalabrutinib||Phase 2|
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of investigational drugs to learn whether the drugs work in treating a specific disease. "Investigational" means that the drugs are being studied. The FDA (the U.S. Food and Drug Administration) has not approved acalabrutinib for CLL, although it is FDA-approved for patients with relapsed mantle cell lymphoma. The FDA has approved venetoclax and obinutuzumab separately for the treatment of patients with CLL. However, the FDA has not approved the combination of these three drugs together (acalabrutinb, venetoclax, and obinutuzumab) as a treatment for any disease. This combination is investigational. In this research study, the investigators are trying to learn if giving the three drugs together can safely and effectively treat CLL.
Acalabrutinib is a type of drug called a kinase inhibitor. It blocks a type of protein called Bruton Tyrosine Kinase (BTK) that helps CLL cells live and grow. By blocking BTK, acalabrutinib may kill cancer cells or stop them from growing. As of September 2017, acalabrutinib has been administered to more than 2,000 people including healthy volunteers, patients with cancers, and patients with rheumatoid arthritis. A few hundred patients with CLL have been treated with acalabrutinib as a single drug, and some of these patients had improvement of their cancer with this treatment.
Obinutuzumab is a type of drug called a monoclonal antibody. It targets a protein on the surface of the CLL cell, causing it to die. Obintuzumab has already been shown to be safe and effective at treating CLL, and is FDA-approved when given together with chemotherapy.
Venetoclax is an oral drug that blocks the function of a protein called BCL-2. CLL cancer cells are thought to depend on the BCL-2 protein for their survival. By blocking BCL-2, venetoclax may kill cancer cells or stop them from growing. Venetoclax has been shown to be safe and effective when given alone to treat patients with CLL and is FDA-approved for patients with CLL after their disease has worsened after at least 1 prior therapy.
If, after 15 or 24 cycles of this investigational therapy, participants have a complete response to the drugs in this trial -- meaning that the investigators cannot detect any CLL using CT scans, bone marrow biopsy and a sensitive test called minimal residual disease (MRD) testing -- participants will stop therapy with acalabrutinib and venetoclax. The investigators will continue to monitor participants while they are off of therapy, and if the CLL comes back participants will be able to restart acalabrutinib and venetoclax. The use of MRD testing to identify small amounts of CLL is investigational, meaning that it has not been FDA-approved. The use of results from this test to guide the decision to stop and re-start therapy, as is done in the trial here, is also investigational.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||37 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Study of Acalabrutinib, Venetoclax, and Obinutuzumab (AVO) for Initial Therapy of Chronic Lymphocytic Leukemia|
|Actual Study Start Date :||July 30, 2018|
|Estimated Primary Completion Date :||January 31, 2022|
|Estimated Study Completion Date :||January 31, 2026|
Venetoclax is an oral drug that blocks the function of a protein called BCL-2. CLL cancer cells are thought to depend on the BCL-2 protein for their survival. By blocking BCL-2, venetoclax may kill cancer cells or stop them from growing.
Other Name: Venclexta
Obinutuzumab is a type of drug called a monoclonal antibody. It targets a protein CD20 on the surface of the CLL cell, causing it to die
Other Name: Gazyva
Acalabrutinib is a type of drug called a kinase inhibitor. It blocks a type of protein called Bruton Tyrosine Kinase (BTK) that helps CLL cells live and grow
Other Name: Calquence
- The rate of bone marrow minimal residual disease (MRD) negative complete response [ Time Frame: After 15 months ]By 4 color flow cytometry
- Rate of Partial Response [ Time Frame: After 3, 8, 15 and 24 months ]By 2018 IW-CLL criteria
- Rate of Complete Response [ Time Frame: After 15 and 24 months ]By 2018 IW-CLL criteria
- Progression free survival [ Time Frame: At 24 months ]By 2018 IW-CLL criteria
- Overall survival [ Time Frame: At 24 months ]
- Rate of peripheral blood MRD [ Time Frame: After 8, 15 and 24 months ]By flow cytometry
- Time to MRD-positive disease recurrence in the peripheral blood [ Time Frame: From date of treatment discontinuation until the date of first documented MRD-positive disease in the blood, assessed up to 120 months ]By flow cytometry
- Time to clinical disease progression [ Time Frame: From date of treatment discontinuation until the date of first documented clinical disease progression, assessed up to 120 months ]By 2018 IW-CLL criteria
- Rate of infusion related reactions [ Time Frame: After 6 months of obinutuzumab ]By CTCAE v4
- Rate of tumor lysis syndrome [ Time Frame: Through study completion, an average of 2 years ]By Howard criteria
- Rate of bone marrow MRD [ Time Frame: After 8 and after 24 months ]By 4 color flow cytometry
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03580928
|Contact: Victoria Patterson, RN||617-632-2399||VPATTERSON@PARTNERS.ORG|
|United States, Massachusetts|
|Dana Farber Cancer Institute||Recruiting|
|Boston, Massachusetts, United States, 02215|
|Contact: Matthew S. Davids, MD, MMSc|
|Principal Investigator: Matthew S. Davids, MD, MMSc|
|Principal Investigator:||Matthew S. Davids, MD, MMSc||Dana-Farber Cancer Institute|