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AzTrials

Chronic Lymphocytic LeukemiaPhase 3AMPLIFYNCT03836261

Study of Acalabrutinib (ACP-196) in Combination With Venetoclax (ABT-199), With and Without Obinutuzumab (GA101) Versus Chemoimmunotherapy for Previously Untreated CLL

A Phase 3 study testing Acalabrutinib, Venetoclax and Chemoimmunotherapy in people with Chronic Lymphocytic Leukemia, run by Acerta Pharma BV at 169 sites in 27 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

The purpose of this study is to evaluate the efficacy and safety of acalabrutinib in combination with venetoclax and acalabrutinib in combination with venetoclax with and without obinutuzumab compared to chemoimmunotherapy in subjects with previously untreated CLL Read more about this study

Who is it for?
Ages 18 to 130 years
Conditions the study is for
Chronic Lymphocytic Leukemia
What is being tested?
Acalabrutinib, Venetoclax and Chemoimmunotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
984 participants
Where
169 sitesin 27 countries
Study dates
25 Feb 2019to 30 Apr 2027
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 130 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Men and women ≥18 years of age.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  • Diagnosis of CLL that meets published diagnostic criteria (Hallek et al. 2018)
  • Active disease per IWCLL 2018 criteria that requires treatment.
  • Participants must use highly effective birth control throughout the study.

Who cannot join

  • Any prior CLL-specific therapies.
  • Detected del(17p) or TP53 mutation.
  • Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL) (e.g., Richter's transformation, prolymphocytic leukemia [PLL], or diffuse large B cell lymphoma [DLBCL]), or central nervous system (CNS) involvement by leukemia.
  • History of confirmed progressive multifocal leukoencephalopathy (PML).
  • Received any investigational drug within 30 days before first dose of study drug.
  • Major surgical procedure within 30 days before the first dose of study drug.
Show all 17Show fewer
  • Significant cardiovascular disease such as symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 or 4 cardiac disease. Note: Subjects with controlled, asymptomatic atrial fibrillation are allowed to enroll on study.
  • Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach, or extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
  • Received a live virus vaccination within 28 days of first dose of study drug.
  • Known history of infection with human immunodeficiency virus (HIV).
  • Serologic status reflecting active hepatitis B or C infection.
  • History of known hypersensitivity or anaphylactic reactions to study drugs or excipients.
  • History of stroke or intracranial hemorrhage within 6 months before first dose of study drug.
  • Known bleeding disorders.
  • Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists.
  • Female participants must not be breastfeeding or pregnant.
  • Concurrent participation in another therapeutic clinical trial.

Trial locations and contacts

169 sites in 27 countries.

169 sites in 27 countries

China22 sites

  • Research Site

    Beijing, 100034

  • Research Site

    Beijing, 100044

  • Research Site

    Beijing, 100191

  • Research Site

    Changchun, 130021

  • Research Site

    Changsha, 410008

  • Research Site

    Chengdu, 610041

  • Research Site

    Chongqing, 400037

  • Research Site

    Guangzhou, 510100

  • Research Site

    Guangzhou, 510515

  • Research Site

    Hangzhou, 310003

  • Research Site

    Nanchang, 330006

  • Research Site

    Nanjing, 210029

  • Research Site

    Shenyang, 110001

  • Research Site

    Shenyang, 110134

  • Research Site

    Tianjin, 301600

  • Research Site

    Ürümqi, 830054

  • Research Site

    Wenzhou, 325000

  • Research Site

    Wuhan, 430022

  • Research Site

    Wuhan, 430030

  • Research Site

    Xi'an, 710061

  • Research Site

    Zhengzhou, 450008

  • Research Site

    Zhengzhou, 450052

Other trials in China

United States16 sites

  • Research Site

    Baltimore, Maryland, 21201

  • Research Site

    Boston, Massachusetts, 02215

  • Research Site

    Canton, Ohio, 44718

  • Research Site

    Charlotte, North Carolina, 28204

  • Research Site

    Fort Sam Houston, Texas, 78234

  • Research Site

    Fort Wayne, Indiana, 46804

  • Research Site

    Los Angeles, California, 90095

  • Research Site

    Louisville, Kentucky, 40207

  • Research Site

    New Orleans, Louisiana, 70056

  • Research Site

    New York, New York, 10021

  • Research Site

    Pittsburgh, Pennsylvania, 15224

  • Research Site

    Pittsburgh, Pennsylvania, 15232

  • Research Site

    Redondo Beach, California, 90277

  • Research Site

    Spokane, Washington, 99208

  • Research Site

    Tacoma, Washington, 98405

  • Research Site

    Wichita, Kansas, 67214

Other trials in United States

Brazil9 sites

  • Research Site

    Goiânia, 74605-020

  • Research Site

    Porto Alegre, 90020-090

  • Research Site

    Porto Alegre, 90035-003

  • Research Site

    Porto Alegre, 90110-270

  • Research Site

    Rio de Janeiro, 20230-130

  • Research Site

    Rio de Janeiro, 22793-080

  • Research Site

    São Paulo, 01236-030

  • Research Site

    São Paulo, 01308-050

  • Research Site

    São Paulo, 05403-010

Other trials in Brazil

Russia9 sites

  • Research Site

    Moscow, 115478

  • Research Site

    Moscow, 125284

  • Research Site

    Saint Petersburg, 191024

  • Research Site

    Saint Petersburg, 197341

  • Research Site

    Saint Petersburg, 197347

  • Research Site

    Samara, 443095

  • Research Site

    Sochi, 354057

  • Research Site

    Tula, 300053

  • Research Site

    Volgograd, 400138

Other trials in Russia

Spain9 sites

  • Research Site

    Badalona, 08916

  • Research Site

    Barcelona, 08035

  • Research Site

    Barcelona, 08041

  • Research Site

    Madrid, 28007

  • Research Site

    Madrid, 28031

  • Research Site

    Majadahonda, 28222

  • Research Site

    Salamanca, 37007

  • Research Site

    Santander, 39008

  • Research Site

    Valencia, 46009

Other trials in Spain

Australia8 sites

  • Research Site

    Adelaide, 5000

  • Research Site

    Darlinghurst, 2010

  • Research Site

    Heidelberg, 3084

  • Research Site

    Kogarah, 2217

  • Research Site

    Melbourne, 3000

  • Research Site

    Nedlands, 6009

  • Research Site

    Waratah, 2298

  • Research Site

    Woolloongabba, 4102

Other trials in Australia

Canada8 sites

  • Research Site

    Calgary, Alberta, T2N 5G2

  • Research Site

    Edmonton, Alberta, T6G 1Z2

  • Research Site

    Montreal, Quebec, H4J 1C5

  • Research Site

    Ottawa, Ontario, K1H 8L6

  • Research Site

    Québec, Quebec, G1J 1Z4

  • Research Site

    Toronto, Ontario, M4N 3M5

  • Research Site

    Toronto, Ontario, M5G 2M9

  • Research Site

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

France8 sites

  • Research Site

    Montpellier, 34090

  • Research Site

    Paris, 75013

  • Research Site

    Paris, 75015

  • Research Site

    Paris, 75475

  • Research Site

    Rennes, 35033

  • Research Site

    Rouen, 76038

  • Research Site

    Toulouse, 31059

  • Research Site

    Villejuif, 94800

Other trials in France

Poland8 sites

  • Research Site

    Brzozów, 36-200

  • Research Site

    Bydgoszcz, 85-048

  • Research Site

    Gdynia, 81-519

  • Research Site

    Krakow, 30-727

  • Research Site

    Lodz, 93-510

  • Research Site

    Lublin, 20-081

  • Research Site

    Wroclaw, 50-367

  • Research Site

    Wroclaw, 50-556

Other trials in Poland

Czechia6 sites

  • Research Site

    Brno, 625 00

  • Research Site

    Hradec Králové, 500 05

  • Research Site

    Olomouc, 779 00

  • Research Site

    Ostrava - Poruba, 70852

  • Research Site

    Plzen - Lochotin, 304 60

  • Research Site

    Prague

Other trials in Czechia

Israel6 sites

  • Research Site

    Haifa, 31999

  • Research Site

    Jerusalem, 91120

  • Research Site

    Jerusalem

  • Research Site

    Petah Tikva, 49100

  • Research Site

    Tel Aviv, 64239

  • Research Site

    Tel HaShomer, 52620

Other trials in Israel

Italy6 sites

  • Research Site

    Meldola, 47014

  • Research Site

    Milan, 20132

  • Research Site

    Milan, 20162

  • Research Site

    Novara, 28100

  • Research Site

    Ravenna, 48121

  • Research Site

    Torino, 10126

Other trials in Italy

Netherlands5 sites

  • Research Site

    's-Hertogenbosch, 5223 GZ

  • Research Site

    Almere Stad, 1315 RA

  • Research Site

    Amsterdam, 1081 HV

  • Research Site

    Arnhem, 6815 AD

  • Research Site

    Breda, 4818 CK

Other trials in Netherlands

South Africa5 sites

  • Research Site

    Bloemfontein, 9301

  • Research Site

    Cape Town, 7925

  • Research Site

    Pretoria, 0044

  • Research Site

    Randburg, 2125

  • Research Site

    Soweto, 2013

Other trials in South Africa

South Korea5 sites

  • Research Site

    Incheon, 21565

  • Research Site

    Seoul, 03080

  • Research Site

    Seoul, 03722

  • Research Site

    Seoul, 05505

  • Research Site

    Seoul, 06591

Other trials in South Korea

Taiwan5 sites

  • Research Site

    Kaohsiung City, 833

  • Research Site

    Taichung, 404

  • Research Site

    Tainan, 70403

  • Research Site

    Taipei, 10002

  • Research Site

    Taipei, 11217

Other trials in Taiwan

Turkey (Türkiye)5 sites

  • Research Site

    Ankara, 06100

  • Research Site

    Ankara

  • Research Site

    Izmir, 35340

  • Research Site

    Kurupelit, 55139

  • Research Site

    Talas, 38280

Other trials in Turkey (Türkiye)

Argentina4 sites

  • Research Site

    Buenos Aires, 1114

  • Research Site

    Capital Federal, 1118

  • Research Site

    Ciudad de Buenos Aires, C1426ANZ

  • Research Site

    Córdoba, 5000

Other trials in Argentina

Hungary4 sites

  • Research Site

    Budapest, 1083

  • Research Site

    Budapest, 1088

  • Research Site

    Debrecen, 4032

  • Research Site

    Kaposvár, 7400

Other trials in Hungary

Austria3 sites

  • Research Site

    Krems, 3500

  • Research Site

    Salzburg, 5020

  • Research Site

    Vienna, 1140

Other trials in Austria

Bulgaria3 sites

  • Research Site

    Plovdiv, 4000

  • Research Site

    Sofia, 1606

  • Research Site

    Vratsa, 3000

Other trials in Bulgaria

Denmark3 sites

  • Research Site

    Aarhus, 8200

  • Research Site

    Copenhagen, 2100

  • Research Site

    Roskilde, 4000

Other trials in Denmark

Saudi Arabia3 sites

  • Research Site

    Dammam, 31444

  • Research Site

    Jeddah, 21423

  • Research Site

    Riyadh, 12713

Other trials in Saudi Arabia

Sweden3 sites

  • Research Site

    Gothenburg, 41345

  • Research Site

    Örebro, 70185

  • Research Site

    Uppsala, 75185

Other trials in Sweden

United Kingdom3 sites

  • Research Site

    Cambridge, CB2 0QQ

  • Research Site

    Canterbury, CT1 3NG

  • Research Site

    Wolverhampton, WV10 OQP

Other trials in United Kingdom

Germany2 sites

  • Research Site

    Paderborn, 33098

  • Research Site

    Würzburg, 97080

Other trials in Germany

Slovakia1 site

  • Research Site

    Bratislava, 83310

Other trials in Slovakia

About this study

Official title: A Randomized, Multicenter, Open-Label, Phase 3 Study to Compare the Efficacy and Safety of Acalabrutinib (ACP-196) in Combination With Venetoclax With and Without Obinutuzumab Compared to Investigator's Choice of Chemoimmunotherapy in Subjects With Previously Untreated Chronic Lymphocytic Leukemia Without Del(17p) or TP53 Mutation (AMPLIFY)

The purpose of this study is to evaluate the efficacy and safety of acalabrutinib in combination with venetoclax and acalabrutinib in combination with venetoclax with and without obinutuzumab compared to chemoimmunotherapy in subjects with previously untreated CLL

Read the detailed description

This randomized, global, multicenter, open-label, Phase 3 study will evaluate the efficacy and safety of AV and AVG versus chemoimmunotherapy (FCR or BR) in subjects with previously untreated CLL without del(17p) or TP53. Subjects will be randomized in a 1:1:1 ratio into 3 arms through a block stratified randomization procedure.

The study includes screening (35 days), treatment (from randomization until study drug discontinuation) and follow-up phase.

Being tested
Acalabrutinib, Venetoclax, Chemoimmunotherapy, Obinutuzumab
Keywords
CLL, Chronic Leukemia Lymphocytic, Leukemia
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, B-Cell, Leukemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AcalabrutinibDrug

    Also called Calquence (acalabrutinib)

    Acalabrutinib,

  • VenetoclaxDrug

    Also called Venclyxto, Venclexta

    Venetoclax

  • ChemoimmunotherapyDrug

    fludarabine/cyclophosphamide/rituximab (FCR), bendamustine/rituximab (BR)

  • ObinutuzumabDrug

    Also called Gazyva, Gazyvaro

    Obinutuzumab

Study groups in NCT03836261
Study groupRoleWhat they receive
Acalabrutinib, VenetoclaxExperimentalAcalabrutinib in combination with Venetoclax
Receives: Drug: Acalabrutinib; Drug: Venetoclax
Acalabrutinib, Venetoclax, ObinutuzumabExperimentalAcalabrutinib in combination with Venetoclax with Obinutuzumab
Receives: Drug: Acalabrutinib; Drug: Venetoclax; Drug: Obinutuzumab
ChemoimmunotherapyActive comparatorChemoimmunotherapy FCR: Fludarabine, Cyclophosphamide and Rituximab BR: Bendamustine and Rituximab
Receives: Drug: Chemoimmunotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To evaluate the efficacy of acalabrutinib with venetoclax (Arm A) compared to chemoimmunotherapy fludarabine/cyclophosphamide/rituximab [FCR] or bendamustine/rituximab [BR] (Arm C): PFS

    Progression-free survival (PFS) after randomization, defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the Independent Review Committee (IRC) according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 criteria

    Measured: 6 years

Secondary outcomes (2)

  1. To evaluate the efficacy of acalabrutinib with venetoclax in combination with obinutuzumab (Arm B) compared with FCR or BR (Arm C): PFS

    PFS after randomization, defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the IRC assessment and investigator assessment

    Measured: 6 years

  2. To evaluate the efficacy of acalabrutinib with venetoclax (Arm A) compared with FCR or BR (Arm C): PFS defined the same as above per investigator assessment.

    PFS after randomization, defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the IRC assessment and investigator assessment

    Measured: 6 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Feb 2019
  2. Study start25 Feb 2019
  3. Primary completion30 Apr 2027 (estimated)
  4. Study completion30 Apr 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
984 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03836261
Sponsor's protocol ID
ACE-CL-311
Other IDs
D8221C00001, 2023-509349-11-00, 2018-002443-28, 2018, 2023
Acronym
AMPLIFY
Status last verified
Sep 2026
First submitted
6 Feb 2019
Last updated
5 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Brown JR, Seymour JF, Jurczak W, Aw A, Wach M, Illes A, Tedeschi A, Owen C, Skarbnik A, Lysak D, Eom KS, Simkovic M, Pavlovsky MA, Kater AP, Eichhorst B, Miller K, Munugalavadla V, Yu T, de Borja M, Ghia P; AMPLIFY investigators; AMPLIFY Investigators. Fixed-Duration Acalabrutinib Combinations in Untreated Chronic Lymphocytic Leukemia. N Engl J Med. 2025 Feb 20;392(8):748-762. doi: 10.1056/NEJMoa2409804. Epub 2025 Feb 5.

    PubMed 39976417

  • Alfaifi A, Bahashwan S, Alsaadi M, Ageel AH, Ahmed HH, Fatima K, Malhan H, Qadri I, Almehdar H. Advancements in B-Cell Non-Hodgkin's Lymphoma: From Signaling Pathways to Targeted Therapies. Adv Hematol. 2024 Nov 12;2024:5948170. doi: 10.1155/2024/5948170. eCollection 2024.

    PubMed 39563886

  • Davids MS, Lampson BL, Tyekucheva S, Wang Z, Lowney JC, Pazienza S, Montegaard J, Patterson V, Weinstock M, Crombie JL, Ng SY, Kim AI, Jacobson CA, LaCasce AS, Armand P, Arnason JE, Fisher DC, Brown JR. Acalabrutinib, venetoclax, and obinutuzumab as frontline treatment for chronic lymphocytic leukaemia: a single-arm, open-label, phase 2 study. Lancet Oncol. 2021 Oct;22(10):1391-1402. doi: 10.1016/S1470-2045(21)00455-1. Epub 2021 Sep 14.

    PubMed 34534514

  • Gordon MJ, Danilov AV. The evolving role of Bruton's tyrosine kinase inhibitors in chronic lymphocytic leukemia. Ther Adv Hematol. 2021 Jan 30;12:2040620721989588. doi: 10.1177/2040620721989588. eCollection 2021.

    PubMed 33796237

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Acalabrutinib, Venetoclax and Chemoimmunotherapy in people with Chronic Lymphocytic Leukemia, run by Acerta Pharma BV at 169 sites in 27 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 5 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 169 sites in China, United States, Brazil, Russia, Spain and 22 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To evaluate the efficacy of acalabrutinib with venetoclax (Arm A) compared to chemoimmunotherapy fludarabine/cyclophosphamide/rituximab [FCR] or bendamustine/rituximab [BR] (Arm C): PFS (time frame: 6 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03836261, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2026.

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