Venetoclax-Obinutuzumab +/- Acalabrutinib in R/R CLL
A Phase 2 Study of MRD Adapted Therapy With Venetoclax-obinutuzumab in Patients With High or Intermediate BALL Risk Relapsed or Refractory CLL, With Addition of Acalabrutinib in Patients Who Fail to Achieve MRD Eradication
1 other identifier
interventional
40
1 country
3
Brief Summary
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Oct 2020
Longer than P75 for phase_2
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 17, 2020
CompletedFirst Posted
Study publicly available on registry
September 23, 2020
CompletedStudy Start
First participant enrolled
October 19, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 1, 2029
April 13, 2026
April 1, 2026
7.4 years
September 17, 2020
April 9, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of participants alive at 1 year
Percent of participants with high and intermediate risk relapsed/refractory CLL who are alive at 1 year. The percent of patients who are alive at one-year (rOS) will be measured by monitoring you in clinic. An rOS of at least 90% will be considered promising whereas the rOS of 75% or less will be considered non-promising.
1 year
Secondary Outcomes (7)
Overall Response Rate
1 year
Complete response rate
1 year
Frequency of undetectable minimum residual disease (uMRD) after 12 Months
1 year
Undetectable MRD rate with addition of acalabrutinib to venetoclax-obinutuzumab among patients who fail to eradicate MRD with venetoclax-obinutuzumab
12 months
Progression-free Survival
6 years
- +2 more secondary outcomes
Study Arms (1)
Venetoclax-Obinutuzumab +/- Acalabrutinib
EXPERIMENTALA 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)
Interventions
Tablet, taken by mouth
Capsule, taken by mouth
Eligibility Criteria
You may qualify if:
- Diagnosis of CLL or SLL according to WHO criteria
- Participants must require therapy according to iwCLL 2018 guidelines
- Participants must have ≥ 2 points (high or intermediate risk disease) according to the CLL
- BALL Risk Model:
- Beta-2 microglobulin If ≥ 5 mg/L, assign 1 point
- Lactate dehydrogenase If \>institutional upper limit of normal, assign 1 point
- Hemoglobin If \<11 g/dL (female) or \<12 g/dL (male), assign 1 point
- Time from start of last therapy If \<24 months, assign 1 point, If 4 points, patient is high risk, If 2-3 points, patient is intermediate risk, If 0-1 points, patient is low risk
- Participants must have received prior systemic therapy for CLL
- Age over 18 years
- ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
- Participants must have adequate organ function as defined below:
- total bilirubin ≤2 × institutional upper limit of normal unless considered secondary to Gilbert's syndrome, in which case ≤3 x ULN
- AST(SGOT)/ALT(SGPT) ≤2 × institutional upper limit of normal
- creatinine within normal institutional limits OR
- +10 more criteria
You may not qualify if:
- Prior therapy with a BTK inhibitor (e.g. acalabrutinib) or BCL2 inhibitor (e.g. venetoclax), with the following exception:
- Patients with undetectable MRD by flow cytometry at 10 (peripheral blood or bone marrow) or CR from prior treatment with BCL2 inhibitor (with or without BTK inhibitor) are eligible. Note: Patients who received prior BTK inhibitor therapy alone are not eligible.
- Known hypersensitivity (IgE-mediated) reaction to obinutuzumab or to any of its excipients
- Participants who are receiving any other investigational agents unless authorized by the overall study principal investigator
- Known active histological transformation from CLL to an aggressive lymphoma (i.e., Richter's transformation)
- Active malignancy or systemic therapy for another malignancy within 3 years; local/regional therapy with curative intent such as surgical resection or localized radiation within 3 years of treatment is permitted; active prostate cancer that is considered low-risk and appropriate for continued active surveillance strategy is permitted.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 2 weeks prior to Cycle 1, Day 1
- Known bleeding diathesis
- Pregnant women are excluded from this study because the study agents have potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the study agents, breastfeeding should be discontinued if the mother is treated with study therapy.
- Prior major surgical procedure within 4 weeks of study, or anticipation of need for a major surgical procedure during the course of the study
- Known CNS hemorrhage or stroke within 6 months of the study
- History of progressive multifocal leukoencephalopathy (PML)
- History of HIV infection or active hepatitis B (chronic or acute) or hepatitis C infection
- Patients with occult or prior HBV infection (defined as positive total hepatitis B core antibody \[HBcAb\] and negative HBsAg) may be included if HBV DNA is undetectable. These patients must be willing to take appropriate anti-viral prophylaxis as indicated and undergo monthly DNA testing.
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Massachusetts General Hospitallead
- Genentech, Inc.collaborator
Study Sites (3)
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Related Publications (1)
Soumerai JD, Ni A, Darif M, Londhe A, Xing G, Mun Y, Kay NE, Shanafelt TD, Rabe KG, Byrd JC, Chanan-Khan AA, Furman RR, Hillmen P, Jones J, Seymour JF, Sharman JP, Ferrante L, Mobasher M, Stark T, Reddy V, Dreiling LK, Bhargava P, Howes A, James DF, Zelenetz AD. Prognostic risk score for patients with relapsed or refractory chronic lymphocytic leukaemia treated with targeted therapies or chemoimmunotherapy: a retrospective, pooled cohort study with external validations. Lancet Haematol. 2019 Jul;6(7):e366-e374. doi: 10.1016/S2352-3026(19)30085-7. Epub 2019 May 17.
PMID: 31109827BACKGROUND
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jacob D Soumerai, MD
Massachusetts General Hospital
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
September 17, 2020
First Posted
September 23, 2020
Study Start
October 19, 2020
Primary Completion (Estimated)
March 1, 2028
Study Completion (Estimated)
March 1, 2029
Last Updated
April 13, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Data can be shared no earlier than 1 year following the date of publication
- Access Criteria
- Contact the Partners Innovations team at http://www.partners.org/innovation
The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.