About this trial

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

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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).

Symptomatic adenopathy or splenomegaly

Local symptoms due to extranodal disease

Disqualifiers

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)

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.

Trial design

Design model

Single group

Treatments tested in this trial

Acalabrutinib
Drug
Each study drug is given according to a different schedule: Acalabrutinib: Oral, dosage per protocol, start cycle 1 and beyond according to schedule outlined in protocol
Venetoclax
Drug
Venetoclax: oral. daily, dosage per protocol, start cycle 3 and beyond according to schedule outlined in protocol
Obinutuzumab
Drug
Obinutuzumab: intravenous infusion, dosage per protocol, drug during cycles 2 and beyond according to schedule outlined in protocol

Treatment groups

72 Participants

are divided into 1 treatment group

Group A: Acalabrutinib, Venetoclax, and ObinutuzumabExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

Recommended Phase 2 Dose for acalabrutinib

The RP2D will be defined as the highest dose level for which there are no more than 1/6 DLTs observed.

Time frame

5 months

2

Complete Remission Rate

Complete remission (CR) rate after 7 cycles of treatment with AVO in treatment naïve (TN) transplant ineligible MCL and TN transplant-eligible, TP53 mutated MCL, cohort B. CR rate after 7 cycles of treatment with AVO in TN TP53-mutated MCL, expansion cohort D. Complete remission (CR) is defined radiographically using 2014 Lugano criteria and a negative bone marrow biopsy by histology, immunohistochemistry, and flow cytometry, if bone marrow was initially involved by MCL at screening. CR, a primary endpoint measured after 7 cycles of AVO, does not incorporate minimal residual disease (MRD) testing

Time frame

7 Months

3

MRD negative complete remission rate

Minimal residual disease (MRD) negative (\<1 in 106 cells) CR rate after 7 cycles of treatment with AVO in TN transplant-eligible, TP53 wild type MCL, cohort C

Time frame

7 months

Secondary outcomes

1

CR rate after 7 cycles of treatment with AVO in participants with TN TP53-mutated MCL in cohort B and expansion cohort D

Complete remission (CR) is defined radiographically using 2014 Lugano criteria and a negative bone marrow biopsy by histology, immunohistochemistry, and flow cytometry, if bone marrow was initially involved by MCL at screening. CR, a primary endpoint measured after 7 cycles of AVO, does not incorporate minimal residual disease (MRD) testing

Time frame

7 cycles

2

Complete Remission (CR) rate after 7 cycles in the entire study population

Complete remission (CR) is defined radiographically using 2014 Lugano criteria and a negative bone marrow biopsy by histology, immunohistochemistry, and flow cytometry, if bone marrow was initially involved by MCL at screening. CR, a primary endpoint measured after 7 cycles of AVO, does not incorporate minimal residual disease (MRD) testing

Time frame

7 months

3

CR rate after 7 cycles cohort A and C

Complete remission (CR) is defined radiographically using 2014 Lugano criteria and a negative bone marrow biopsy by histology, immunohistochemistry, and flow cytometry, if bone marrow was initially involved by MCL at screening. CR, a primary endpoint measured after 7 cycles of AVO, does not incorporate minimal residual disease (MRD) testing

Time frame

7 Months

4

Partial Response (PR) Rate after 7 cycles

2014 Lugano Criteria

Time frame

7 months

Avo In R/R And Previously Untreated MCL

About this trial

Eligibility criteria

Qualifiers

Disqualifiers

Trial design

Treatments tested in this trial

Treatment groups

Trial outcomes

Primary outcomes

Secondary outcomes

Other outcomes

Sponsors and contacts