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Recurrent B-Cell Non-Hodgkin LymphomaPhase 1NCT04447716

An Early Phase Study of Venetoclax, Lenalidomide, and Rituximab/Hyaluronidase in Slow-Growing Lymphomas That Have Come Back After Treatment or Have Not Responded to Treatment

A Phase 1 study testing Venetoclax, Lenalidomide and Rituximab in people with Recurrent B-Cell Non-Hodgkin Lymphoma and Recurrent Follicular Lymphoma, run by Thomas Jefferson University at 1 site in United States.

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

This phase I trial studies the side effects and best dose of venetoclax when given together with lenalidomide and rituximab hyaluronidase in treating patients with follicular lymphoma and marginal zone lymphoma that has come back after treatment (relapsed) or has not responded to treatment (refractory). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Venetoclax, Lenalidomide and Rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
1 siteUnited States
Study dates
16 Oct 2020to Mar 2027
Phase
Phase 1
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed informed consent form
  • Ability and willingness to comply with the requirements of the study protocol
  • Able to swallow oral medications whole
  • Patients must have received at least one prior systemic therapy
  • Histologically confirmed indolent B-cell non-Hodgkin's lymphoma (NHL) of any of the following subtypes recognized by the World Health Organization (WHO) classification: Follicular lymphoma and marginal zone lymphoma. Patients with indolent non-Hodgkin's Lymphoma (iNHL) should have received at least 1 previous prior therapy
  • Patients must have an indication for treatment by Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria in the opinion of the investigator
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  • Radiographically measurable disease by computed tomography (CT) scan, defined as at least one node > 1.5 cm in size
  • All study participants must be registered into the mandatory lenalidomide risk evaluation and mitigation strategy (REMS) program, and be willing and able to comply with the requirements of the REMS program
  • Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the lenalidomide REMS program
  • Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation. Patients intolerant to aspirin (ASA) may use low molecular weight heparin or equivalent. Inability to take any form of prophylaxis excludes participation
  • Eastern Cooperative Oncology Group performance status of 0, 1, or 2
  • Hemoglobin >= 9 g/dL (unless caused by underlying disease, as established by extensive bone marrow involvement or as a result of hypersplenism secondary to the involvement of the spleen by lymphoma per the investigator)
  • Absolute neutrophil count >= 1.0 x 10^9/L (unless caused by underlying disease, as established by extensive bone marrow involvement or as a result of hypersplenism secondary to the involvement of the spleen by lymphoma per the investigator)
  • Platelet count >= 75 x 10^9/L (unless caused by underlying disease, as established by extensive bone marrow involvement or as a result of hypersplenism secondary to the involvement of the spleen by lymphoma per the investigator)
  • International normalized ratio > 1.5 x upper limit of normal (ULN) for patients not receiving therapeutic anticoagulation
  • Partial thromboplastin time (PTT) or activated PTT (aPTT) =< 1.5 x ULN
  • Creatinine clearance >= 60 mL/min, calculated with the use of the 24-hour creatinine clearance or modified Cockcroft-Gault equation
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x ULN
  • Total bilirubin =< 1.5 x ULN (or =< 3 x ULN for patients with documented Gilbert syndrome)
  • Women of childbearing potential must have a negative serum or urine pregnancy test result within 14 days prior to registration
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of < 1% per year during the treatment period and for at least 30 days after the last dose of venetoclax and lenalidomide or 12 months after the last dose of rituximab, whichever is longer * Women must refrain from donating eggs during this same period
  • A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (>= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus) * Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices * The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below: * With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least 6 months after the last dose of rituximab and for at least 30 days after the last dose of venetoclax and lenalidomide whichever is longer. Men must refrain from donating sperm during this same period * With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 6 months after the last dose of rituximab to avoid exposing the embryo * The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception

Who cannot join

  • Known hypersensitivity to any of the study drugs study drugs
  • Known central nervous system (CNS) involvement by lymphoma
  • Prior allogeneic stem cell transplant is not permitted if patient is fewer than 4 months from transplant and has either active graft versus host disease or on immunosuppression
  • History of severe allergic reactions to humanized monoclonal antibodies
  • Prior use of lenalidomide or venetoclax or other BCL2 family inhibitors; prior rituximab is allowed as long as they continue to express CD20 and are not rituximab refractory as defined as: * Did not respond (at least a partial response [PR]) to rituximab or rituximab (R)-chemoregimen therapy * Time to disease progression < 6 months after last rituximab dose
  • History of other malignancy that could affect compliance with the protocol or interpretation of results * Patients with a history of curatively treated basal or squamous cell carcinoma or stage 1 melanoma of the skin or in situ carcinoma of the cervix are eligible * Patients with a malignancy that has been treated with surgery alone with curative intent will also be excluded. Individuals in documented remission without treatment for >= 2 years prior to enrollment may be included at the discretion of the investigator
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  • Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results or that could increase risk to the patient, including renal disease that would preclude chemotherapy administration or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
  • 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 4 weeks prior to registration
  • Requires the use of warfarin (because of potential drug-drug interactions that may potentially increase the exposure of warfarin)
  • Received the following agents within 7 days prior to registration: * Steroid therapy for anti-neoplastic intent * Strong and moderate CYP3A inhibitors * Strong and moderate CYP3A inducers * Consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to the first dose of venetoclax
  • Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis Presence of positive test results for hepatitis B virus (HBV), hepatitis B surface antigen (HBsAg), or hepatitis C (HCV) antibody * Patients who are positive for HCV antibody must be negative for HCV by polymerase chain reaction (PCR) to be eligible for study participation * Patients with occult or prior HBV infection (defined as positive total hepatitis B core antibody [HBcAb] and negative HBsAg) may be included if HBV deoxyribonucleic acid (DNA) is undetectable. These patients must be willing to undergo monthly DNA testing.
  • Known infection with human immunodeficiency virus (HIV) or human T-cell leukemia virus 1 (HTLV-1)
  • Receipt of live-virus vaccines within 28 days prior to the initiation of study treatment or need for live-virus vaccines at any time during study treatment
  • Pregnant or lactating, or intending to become pregnant during the study
  • Recent major surgery (within 6 weeks prior to the start of cycle 1, day 1) other than for diagnosis
  • Malabsorption syndrome or other condition that precludes enteral route of administration
  • Known allergy to both xanthine oxidase inhibitors and rasburicase

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Sidney Kimmel Cancer Center at Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

Official title: A Phase I Study of Venetoclax + Lenalidomide + Rituximab Hyaluronidase in Relapsed or Refractory (R/R) Indolent Non-Hodgkin's Lymphoma (iNHL).

This phase I trial studies the side effects and best dose of venetoclax when given together with lenalidomide and rituximab hyaluronidase in treating patients with follicular lymphoma and marginal zone lymphoma that has come back after treatment (relapsed) or has not responded to treatment (refractory). Venetoclax may stop the growth of cancer cells by blocking the action of a protein called Bcl-2, that helps cancer cells survive. Immunotherapy with lenalidomide, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Immunotherapy with monoclonal antibodies, such as rituximab and rituximab hyaluronidase, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The purpose of this research is to determine if the combination of three drugs, venetoclax, lenalidomide, and rituximab hyaluronidase are safe to administer in patients whose low-grade lymphoma (follicular or marginal zone) has come back after initial therapy or was not responsive to initial therapy.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the safety (and the recommended phase 2 dose [RP2D]), of the combination of venetoclax, lenalidomide, and rituximab hyaluronidase in patients with relapsed/refractory (R/R) follicular lymphoma (FL) and marginal zone lymphoma (MZL).

SECONDARY OBJECTIVES:

  1. To determine the overall response rate (ORR) with rituximab hyaluronidase, venetoclax, and lenalidomide.

II. To determine the 2-year progression-free survival (PFS) with rituximab hyaluronidase, venetoclax, and lenalidomide.

III. To determine the overall survival (OS) following therapy with rituximab hyaluronidase, venetoclax, and lenalidomide.

CORRELATIVE STUDY OBJECTIVES:

  1. Describe changes in the level of expression and expression ratio between anti-apoptotic and pro-apoptotic BCL-2 family members before and after therapy with venetoclax/lenalidomide/rituximab hyaluronidase for each patient.

II. Examine the metabolic landscape before and after venetoclax/lenalidomide/rituximab hyaluronidase and their effects on mitochondrial metabolism.

III. Describe the immune effects of venetoclax and its effects on serum cytokines and different immune cell subsets (e.g. B-cells, T-cells, dendritic cells, etc.) in addition to T-cell activation markers and expression of immune checkpoint proteins.

OUTLINE: This is a dose-escalation study of venetoclax.

Patient receive venetoclax orally (PO) once daily (QD) on days 1-28. Beginning cycle 2, patients receive lenalidomide PO QD on days 1-21. Patients also receive rituximab intravenously (IV) on days 1, 8, 15, and 22 of cycle 2 and rituximab hyaluronidase (if no significant infusion reaction to rituximab) subcutaneously (SC) on day 1 of cycles 4, 6, 8, 10, and 12. Patients may receive rituximab IV (instead of rituximab hyaluronidase) on days 1, 8, 15, and 22 of cycles 4, 6, 8, 10, and 12 if the patient requires rituximab IV in the opinion of the treating physician. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, and then for up to 5 years.

Being tested
Venetoclax, Lenalidomide, Rituximab, Rituximab and Hyaluronidase Human
Medical subject headings
Lymphoma, B-Cell, Lymphoma, Follicular, Lymphoma, B-Cell, Marginal Zone

What participants receive

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

  • VenetoclaxDrug

    Also called 1257044-40-8,, 4-(4-((2-(4-Chlorophenyl)-4, 4-dimethylcyclohex-1-en-1-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)-2-(1H-pyrrolo(2,3-b)pyridin-5-yloxy)benzamide,, ABT-0199,

    Given PO

  • LenalidomideDrug

    Also called 191732-72-6,, 3-(4-Amino-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione,, 703813,, CC-5013

    Given PO

  • RituximabBiological

    Also called 174722-31-7,, 687451,, ABP 798,, BI 695500,

    Given IV

  • Rituximab and Hyaluronidase HumanBiological

    Also called Rituxan Hycela,, Rituximab Plus Hyaluronidase,, Rituximab/Hyaluronidase,, Rituximab/Hyaluronidase Human

    Given SC

Study groups in NCT04447716
Study groupRoleWhat they receive
Treatment (venetoclax, lenalidomide, rituximab, hyaluronidase)ExperimentalPatient receive venetoclax PO QD on days 1-28. Beginning cycle 2, patients receive lenalidomide PO QD on days 1-21. Patients also receive rituximab IV on days 1, 8, 15, and 22 of cycle 2 and rituximab hyaluronidase (if no significant infusion reaction to rituximab) SC on day 1 of cycles 4, 6, 8, 10, and 12. Patients may receive rituximab IV (instead of rituximab hyaluronidase) on days 1, 8, 15, and 22 of cycles 4, 6, 8, 10, and 12 if the patient requires rituximab IV in the opinion of the treating physician. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Venetoclax; Drug: Lenalidomide; Biological: Rituximab; Biological: Rituximab and Hyaluronidase Human

What is being measured

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

  1. Rate of dose-limiting toxicities

    Toxicity incidences assessed and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0, will be tabulated by patient cohort.

    Measured: During the first 56 days of therapy

Secondary outcomes (3)

  1. Overall response rate

    Defined as the sum of the proportions of patients achieving a complete (CR) or partial response (PR) according to the Lugano Response Criteria. Analyses of efficacy outcomes will be descriptive. A 90% confidence interval will be computed for the best response rate (CR+PR rate) during the 12 month treatment period.

    Measured: At the end of 12 month treatment period

  2. Progression-free survival (PFS)

    PFS distributions will be estimated using the Kaplan-Meier method, and the median PFS along with its corresponding 95% confidence interval will be reported.

    Measured: Time from study registration to documented disease progression or death from any cause, assessed at 2 years

  3. Overall survival (OS)

    OS distributions will be estimated using the Kaplan-Meier method, and the median OS along with its corresponding 95% confidence interval will be reported.

    Measured: Time from study registration to death from any cause, assessed at 2 years

Timeline

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

  1. First posted25 Jun 2020
  2. Study start16 Oct 2020
  3. Primary completion16 May 2024
  4. Study completionMar 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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04447716
Sponsor's protocol ID
19P.835
Other IDs
JT 14408
Status last verified
Sep 2026
First submitted
9 Apr 2020
Last updated
2 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Venetoclax, Lenalidomide and Rituximab in people with Recurrent B-Cell Non-Hodgkin Lymphoma and Recurrent Follicular Lymphoma, run by Thomas Jefferson University at 1 site 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 23 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 2 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 1 site 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 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.

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?

Rate of dose-limiting toxicities (time frame: During the first 56 days of therapy). 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 NCT04447716.

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 2 Oct 2026.

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