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Non Hodgkin LymphomaPhase 1/2R/RNCT04419389

APR-246 in Combination With Acalabrutinib or Venetoclax Based Therapy in Subjects With R/R Non Hodgkin Lymphomas (NHL)

A Phase 1/2 study testing APR-246 (eprenetapopt) + Acalabrutinib in CLL, APR-246 (eprenetapopt) 4.5 g/d + Venetoclax + Rituximab in CLL and APR-246 (eprenetapopt) 4.5 g/d + (Acalabrutinib, OR, (Venetoclax +Rituximab)), in CLL and/or MCL and/or RT in people with Non Hodgkin Lymphoma and Chronic Lymphocytic Leukemia, run by Aprea Therapeutics at 4 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Study to determine the preliminary safety, tolerability, and pharmacokinetic (PK) profile of APR-246 in combination with either acalabrutinib or venetoclax + rituximab therapy in subjects with NHL, including relapsed and/or refractory (R/R) CLL and R/R MCL. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
APR-246 (eprenetapopt) + Acalabrutinib in CLL, APR-246 (eprenetapopt) 4.5 g/d + Venetoclax + Rituximab in CLL and APR-246 (eprenetapopt) 4.5 g/d + (Acalabrutinib, OR, (Venetoclax +Rituximab)), in CLL and/or MCL and/or RT
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
4 sitesUnited States
Study dates
2 Mar 2021to 24 Aug 2021
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Is able to understand and is willing and able to comply with the study requirements and to provide written informed consent.
  • Documented histologic diagnosis of R/R CLL, RT, or R/R MCL
  • Safety Lead-In Cohort 1: Patients whose most recent regimen did not include BTK inhibitor therapy.
  • Safety Lead-In Cohort 2: Patients whose most recent regimen did not include Bcl-2 inhibitor therapy.
  • Safety Lead-In Cohort 3: APR-246 + venetoclax + rituximab in patients with RT
  • Prothrombin time (or international normalized ratio) and partial thromboplastin time not to exceed 1.2 × the institution's normal range.
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  • Adequate BM function independent of growth factor or transfusion support, per local laboratory reference range at screening as follows:
  • platelet count ≥ 75 000/mm3;
  • absolute neutrophil count (ANC) ≥ 1000/mm3 unless cytopenia is clearly due to marrow involvement from CLL or MCL
  • total hemoglobin ≥ 9 g/dL (without transfusion support within 2 weeks of screening);
  • Adequate organ function as defined by the following laboratory values:
  • Creatinine clearance ≥ 30 mL/min.
  • Total serum bilirubin ≤ 1.5 × upper limit of normal (ULN) unless due to Gilbert's syndrome, NHL organ involvement, controlled immune hemolysis or considered an effect of regular blood transfusions.
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN, unless due to NHL organ involvement.
  • Age ≥18 years at the time of signing the informed consent form.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
  • Projected life expectancy of ≥ 12 weeks.
  • Women of childbearing potential and men with female partners of childbearing potential must be willing to use an effective form of contraception.

Who cannot join

  • Patient with known allergies to xanthine oxidase inhibitors and/or rasburicase.
  • For patients to receive rituximab on this protocol, prior allergy to rituximab is prohibited.
  • No concomitant anticancer therapies, immunotherapies, cellular, or radiotherapy. No major surgery within 3 weeks prior to first dose of study treatment.
  • Uncontrolled autoimmune hemolytic anemia (AIHA) or immune thrombocytopenia.
  • Consumption of grapefruit, grapefruit products, Seville oranges, or star fruit within 7 days of starting study treatment.
  • Concomitant steroids for disease related pain control are allowed at any dose but must be discontinued prior to any study treatment initiation. Chronic use of corticosteroids is allowed up to ≤ 20 mg prednisone daily for non-cancer related conditions at the time of study start.
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  • History of allogeneic or autologous stem cell transplant (SCT) or CAR-T therapy within the last 30 days or with any of the following:
  • Active graft versus host disease (GVHD)
  • Cytopenias from incomplete blood cell count recovery post-transplant;
  • Need for anti-cytokine therapy for residual symptoms of neurotoxicity > grade 1 from CAR-T therapy;
  • Ongoing immunosuppressive therapy.
  • Known history of human immunodeficiency virus (HIV) serum positivity.
  • Active hepatitis B/C.
  • Known central nervous system (CNS) involvement by lymphoma. Patients with previous treatment for CNS involvement who are neurologically stable and without evidence of disease may be eligible if a compelling clinical rationale is provided to sponsor.
  • Known neurologic disorder or residual neurologic toxicities that may put patients at increased risk of neurologic toxicity in the opinion of the investigator.
  • Cardiac abnormalities.
  • Concomitant malignancies or previous malignancies with less than a 1 year disease- free interval at the time of signing consent.
  • A female patient who is pregnant or breast-feeding.
  • Active uncontrolled systemic infection.
  • Received an investigational agent within 30 days or within 5 T1/2, whichever is shorter prior to the first dose of study treatment.
  • Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption of ibrutinib or venetoclax.
  • Current treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and/or strong P-gp inhibitors..

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: Phase 1 and Dose Expansion Study of APR-246 in Combination With Acalabrutinib or Venetoclax-based Therapy in Subjects With R/R NHL Including Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL)

Study to determine the preliminary safety, tolerability, and pharmacokinetic (PK) profile of APR-246 in combination with either acalabrutinib or venetoclax + rituximab therapy in subjects with NHL, including relapsed and/or refractory (R/R) CLL and R/R MCL.

Read the detailed description

Phase 1, open-label, dose-finding and cohort expansion study to determine the preliminary safety, tolerability, and pharmacokinetic (PK) profile of APR-246 (eprenetapopt) in combination with either acalabrutinib or venetoclax + rituximab therapy in subjects with NHL, including relapsed and/or refractory (R/R) CLL and R/R MCL.

The study includes a safety lead-in portion followed by an expansion portion in subjects with R/R CLL, Richter Transformation (RT), and R/R MCL.

Being tested
APR-246 (eprenetapopt) + Acalabrutinib in CLL, APR-246 (eprenetapopt) 4.5 g/d + Venetoclax + Rituximab in CLL, APR-246 (eprenetapopt) 4.5 g/d + (Acalabrutinib, OR, (Venetoclax +Rituximab)), in CLL and/or MCL and/or RT, APR-246 (eprenetapopt) 4.5 g/d + Venetoclax + Rituximab in RT
Keywords
APR-246, eprenetapopt
Medical subject headings
Lymphoma, Non-Hodgkin, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Mantle-Cell

What participants receive

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

  • APR-246 (eprenetapopt) + Acalabrutinib in CLLDrug

    APR-246 D1, 8 and 15 of each cycle Acalabrutinib will be given at a standard dose and schedule (APR 246 Monotherapy Lead-in; 4.5 g/d x 2)

  • APR-246 (eprenetapopt) 4.5 g/d + Venetoclax + Rituximab in CLLDrug

    APR-246 D1, 8 and 15 of each cycle Venetoclax + Rituximab will be given at a standard dose and schedule (APR 246 Monotherapy Lead-in; 4.5 g/d x 2)

  • APR-246 (eprenetapopt) 4.5 g/d + (Acalabrutinib, OR, (Venetoclax +Rituximab)), in CLL and/or MCL and/or RTDrug

    APR-246 D1, 8 and 15 of each cycle Acalabrutinib will be given at a standard dose and schedule Venetoclax and Rituxiab will be given at a standard dose and schedule

  • APR-246 (eprenetapopt) 4.5 g/d + Venetoclax + Rituximab in RTDrug

    APR-246 4.5 g/d D1, 8 and 15 of each cycle Venetoclax + Rituximab will be given at a standard dose and schedule

Study groups in NCT04419389
Study groupRoleWhat they receive
Safety Lead-In Cohort 1ExperimentalAPR-246 4.5 g/d + Acalabrutinib in Subjects with R/R CLL (APR 246 Monotherapy Lead-in; 4.5 g/d x 2)
Receives: Drug: APR-246 (eprenetapopt) + Acalabrutinib in CLL
Safety Lead-In Cohort 2ExperimentalAPR-246 4.5 g/d + Venetoclax + Rituximab in Subjects with R/R CLL (APR 246 Monotherapy Lead-in; 4.5 g/d x 2).
Receives: Drug: APR-246 (eprenetapopt) 4.5 g/d + Venetoclax + Rituximab in CLL
Expansion CohortsExperimentalAPR-246 4.5 g/d + (Acalabrutinib, OR, (Ven+R)) in Subjects with R/R TP53-mutant CLL, and/or MCL, and/or RT
Receives: Drug: APR-246 (eprenetapopt) 4.5 g/d + (Acalabrutinib, OR, (Venetoclax +Rituximab)), in CLL and/or MCL and/or RT
Safety Lead-In Cohort 3ExperimentalAPR-246 4.5 g/d + Venetoclax + Rituximab in Subjects with RT
Receives: Drug: APR-246 (eprenetapopt) 4.5 g/d + Venetoclax + Rituximab in RT

What is being measured

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

  1. To Determine the DLT of APR-246 in Combination With Acalabrutinib or in Combination With Venetoclax + Rituximab Therapy in Subjects With NHL, Including Subjects With R/R CLL, RT and R/R MCL.

    The occurrence of DLTs, classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events .

    Measured: Through study completion, approximately 1 year

  2. To Assess the Frequency of Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Related to APR-246 in Combination With Acalabrutinib and With Venetoclax + Rituximab Therapy.

    The frequency of TEAEs and SAEs related to APR-246 in combination with acalabrutinib and with venetoclax + rituximab therapy

    Measured: Through study completion, approximately 6 months

  3. To Determine the Maximum Tolerated Dose (MTD) and the Recommended Phase 2 Dose (RP2D) in Subjects With TP53 Mutant NHL, Including Subjects With R/R CLL, RT and R/R MCL.

    The highest dose of APR-246 with acceptable toxicity (RP2D of APR-246) (the dose producing ≤ 20% of DLT).

    Measured: Through study completion, approximately 1 year

Timeline

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

  1. First posted5 Jun 2020
  2. Study start2 Mar 2021
  3. Primary completion23 Aug 2021
  4. Study completion24 Aug 2021

Why it stopped: Sponsor decision

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04419389
Sponsor's protocol ID
A20-11197
Acronym
R/R
Status last verified
Mar 2025
First submitted
1 Jun 2020
Last updated
17 Mar 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing APR-246 (eprenetapopt) + Acalabrutinib in CLL, APR-246 (eprenetapopt) 4.5 g/d + Venetoclax + Rituximab in CLL and APR-246 (eprenetapopt) 4.5 g/d + (Acalabrutinib, OR, (Venetoclax +Rituximab)), in CLL and/or MCL and/or RT in people with Non Hodgkin Lymphoma and Chronic Lymphocytic Leukemia, run by Aprea Therapeutics at 4 sites in United States.

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 18 inclusion and 22 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: stopped early, as of the sponsor's last update on 17 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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 Determine the DLT of APR-246 in Combination With Acalabrutinib or in Combination With Venetoclax + Rituximab Therapy in Subjects With NHL, Including Subjects With R/R CLL, RT and R/R MCL. (time frame: Through study completion, approximately 1 year). The study lists 3 primary outcomes in all. 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 NCT04419389.

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 17 Mar 2025.

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