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Avo In R/R And Previously Untreated MCL | Clinical Trials | Clareo Health

RECRUITINGPHASE1/PHASE2

Avo In R/R And Previously Untreated MCL

A Phase 1/2 Study of Acalabrutinib, Venetoclax, and Obinutuzumab in Patients With Relapsed/Refractory and Previously Untreated Mantle Cell Lymphoma

NCT04855695•Austin I Kim

View on ClinicalTrials.gov

Summary

This research study is evaluating the combination of three drugs - acalabrutinib, venetoclax, and obinutuzumab - as a possible treatment for relapsed or refractory and untreated mantle cell lymphoma (MCL). The names of the study drugs involved in this study are: * Acalabrutinib * Venetoclax * Obinutuzumab

Detailed Description

This is an open-label, investigator-initiated, single-arm, multi-cohort phase 1/2 study to assess the safety and efficacy of the combination of acalabrutinib, venetoclax, and obinutuzumab (AVO) in relapsed/refractory (R/R) and untreated mantle cell lymphoma (MCL). The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. The names of the study drugs involved in this study are: * Acalabrutinib * Venetoclax * Obinutuzumab Participants will receive study treatment for as long as there are no serious side effects and the disease does not get worse. Participants will be followed for 5 years. It is expected that 72 people will take part in this research study. This is a Phase I/II clinical trial. Phase I clinical trials test the safety of investigational drugs and also tries to define the appropriate dose of investigational drugs to use for further studies. "Investigational" means that the drugs are being studied. * The U.S. Food and Drug Administration (FDA) has not approved venetoclax and obinutuzumab for this specific disease but it has been approved for other uses. * The U.S. Food and Drug Administration (FDA) has approved acalabrutinib as a treatment option for this disease.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Participants must meet the following criteria on screening examination to be eligible to participate in the study:
•Participants must have histologically determined mantle cell lymphoma with pathologic review at the participating institutions, that has either:
•* Relapsed or primary refractory after at least one line of therapy including anti-CD20 monoclonal antibody treatment (part A) or; Had no previous anti-lymphoma therapy other than corticosteroids or radiotherapy (parts B, C, and D).
•* Participants in part A, relapsed or refractory following prior therapy, may have had a prior autologous or allogeneic stem cell transplant and may have been treated with chimeric antigen receptor T-cells (CAR T-cells).
•Participants in parts B, C, and D, without prior anti-lymphoma therapy, must require treatment as defined by any of the following criteria:
•* Symptomatic adenopathy or splenomegaly
•* Local symptoms due to extranodal disease
•* Organ function impairment due to disease involvement, including cytopenias due to marrow involvement (WBC \<1.5x109/L; absolute neutrophil count \[ANC\] \<1.0x109/L, Hgb \<10g/dL; platelets \<100x109/L)
•* Presence of systemic B symptoms (fever, drenching night sweats, or unintentional weight loss ≥ 10% body weight over previous 6 months) or functionally significant fatigue
•Participants in part B without prior anti-lymphoma therapy should be deemed to be ineligible for autologous stem cell transplant by the treating physician and/or have a TP53 mutation detected by next generation sequencing at a variant (mutant) allele fraction above the validated threshold for calling a new variant or high TP53 expression on immunohistochemistry (\>50% positive lymphoma cells)
+19 more criteria

Exclusion Criteria

•Participants who have progressed or relapsed after receiving either a BTK inhibitor or BCL2 inhibitor.
•Participants who are receiving any other investigational agents, or have received investigational agents within 4 weeks (or 3 half-lives, whichever is longer) of beginning treatment.
•Concurrent systemic immunosuppressant therapy (e.g., cyclosporine A, tacrolimus, etc., within 28 days of the first dose of study drug or chronic administration of \>20 mg/day of prednisone equivalent corticosteroid within 7 days of the first dose)
•\-- Note: Glucocorticoids for lymphoma symptom palliation are allowed but must be discontinued at time of initiation of protocol therapy.
•History of severe allergic reactions attributed to compounds of similar chemical or biologic composition to obinutuzumab, venetoclax, or acalabrutinib. Patients with reactions to other CD20 monoclonal antibodies (e.g. rituximab, ofatumumab) are not excluded if they were able to eventually tolerate treatment in an outpatient setting without grade 2 or higher infusion reactions.
•Participants who have a history of other malignancies except:
•* Malignancy treated with curative intent and with no known active disease present and felt to be at low risk for recurrence by treating physician. Current adjuvant hormonal therapy for disease treated with curative intent is permissible.
•* Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
•* Adequately treated carcinoma in situ without evidence of disease.
•* Low-risk prostate cancer on active surveillance
+13 more criteria

Locations (3)

University of Chicago Medical Center

Chicago, Illinois, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Key Dates

Start Date

July 2, 2021

Primary Completion Date

June 30, 2027

Completion Date

December 31, 2027

Last Updated

January 21, 2026

Enrollment

ESTIMATED participants

Conditions

Mantle Cell LymphomaRefractory Lymphoma

Interventions

Acalabrutinib

DRUG

Venetoclax

DRUG

Obinutuzumab

DRUG

Contacts

Austin I Kim, MD

CONTACT

(617) 632-6844 AustinI_Kim@dfci.harvard.edu

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RECRUITINGPHASE2

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: January 21, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Avo In R/R And Previously Untreated MCL

Inclusion Criteria

Exclusion Criteria

Phase II Study of Pirtobrutinib With Venetoclax In Relapsed-Refractory MCL (Mantle Cell Lymphoma) Patients

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