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Richter SyndromePhase 2NCT03054896

A Phase II Study of Venetoclax in Combination With Dose-adjusted EPOCH-R or R-CHOP for Patients With Richter's Syndrome

A Phase 2 study testing Venetoclax, DA-EPOCH-R and R-CHOP in people with Richter Syndrome, run by Dana-Farber Cancer Institute at 3 sites in United States.

Active, not recruiting

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

Official record
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Trial summary

This research study is evaluating the combination of a study drug, venetoclax, and a standard chemotherapy regimen, R-EPOCH or R-CHOP, as a possible treatment for Richter's Syndrome. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Richter Syndrome
What is being tested?
Venetoclax, DA-EPOCH-R and R-CHOP
Could I receive a placebo?
No, everyone receives an active treatment
How many people
69 participants
Where
3 sitesUnited States
Study dates
8 Mar 2017to 1 Dec 2027
Phase
Phase 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

  • Must have a confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma as per IW-CLL 2008 criteria (Hallek et al, 2008) with biopsy proven transformation to diffuse large B cell lymphoma (DLBCL), consistent with Richter's Syndrome.
  • Age greater than or equal to 18 years. Because CLL and Richter's Syndrome are extremely rare in persons <18 years of age, children are excluded from this study.
  • ECOG performance status <2 (see Appendix A)
  • Patients must meet the following hematologic criteria at screening, unless they have significant bone marrow involvement of their malignancy confirmed on biopsy:
  • Absolute neutrophil count ≥1000 cells/mm3 (0.5 x 109/L). Growth factor allowed to achieve
  • Platelet count ≥40,000 cells/mm3 (40 x 109/L) independent of transfusion within 7 days of screening
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  • Subject must have adequate coagulation, renal, and hepatic function, per laboratory reference range at Screening as follows:
  • Creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min using 24-hour urine collection for creatinine clearance
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × ULN;
  • Bilirubin ≤ 1.5 × ULN;
  • Subjects with Gilbert's Syndrome or resolving autoimmune hemolytic anemia may have a bilirubin up to 3.0 × ULN and are still eligible
  • The effects of venetoclax on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Contraception must continue for an additional 30 days post last dose of venetoclax for women, and an additional 90 days post last dose in men. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately and venetoclax must be discontinued immediately.
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception and agreement to refrain from donating eggs, as defined below:
  • Women must remain abstinent or use contraceptive methods 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 12 months after the last dose of chemotherapy, whichever is later. Women must refrain from donating eggs during this same period.
  • A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). The definition of childbearing potential may be adapted for alignment with local guidelines or regulations. 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.
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm, as defined below:
  • With a female partner of childbearing potential who is not pregnant, men who are not surgically sterile 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 90 days after the last dose of venetoclax or 12 months after completion of chemotherapy, whichever is later. Men must refrain from donating sperm during this same period. With a pregnant female partner, men must remain abstinent or use a condom during the treatment period and for at least 90 days after the last dose of venetoclax or 12 months after the last dose of chemotherapy, whichever is later, to avoid exposing the embryo.
  • Patients who have undergone prior allogeneic transplantation are eligible provided they do not have significant active graft versus host disease and that their transplant day 0 is > 6 months from their first dose of chemotherapy
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Patients with the Hodgkin variant transformation of CLL will be excluded
  • History of severe allergic or anaphylactic reactions to monoclonal antibody therapy or to the chemotherapy drugs used in this study (see Appendix D), unless the antibody can be given through a desensitization program in consultation with an allergist
  • Subject has received any of the following within 14 days or 5 drug half-lives (whichever is shortest) prior to the first dose of chemotherapy, or has not recovered to less than Grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy:
  • --Any anti-cancer therapy including chemotherapy, biologic agents for anti-neoplastic treatment (e.g. monoclonal antibodies) or radiotherapy, investigational therapy, including targeted small molecule agents. Patients who are currently receiving treatment with ibrutinib or acalabrutinib may continue this agent until the day prior to starting venetoclax, to reduce the risk of tumor flare on treatment cessation.
  • Received previous treatment with R-CHOP, R-EPOCH, or R-hyper-CVAD
  • History of other malignancies, except:
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  • Malignancy treated with curative intent and with no known active disease present before the first dose of study drug and felt to be at low risk for recurrence by treating physician.
  • 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
  • Concurrent systemic immunosuppressant therapy (eg, cyclosporine A, tacrolimus, etc.) within 28 days of the first dose of study drug.
  • Corticosteroids are allowed, but must be dosed at prednisone 20 mg (or equivalent) or lower prior to the start of chemotherapy.
  • Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
  • Known bleeding disorders (eg, von Willebrand's disease) or hemophilia.
  • History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
  • History of human immunodeficiency virus (HIV) or Human T-Cell Leukemia Virus 1 (HTLV-1), or active hepatitis C virus (HCV) or hepatitis B virus (HBV). Patients who are positive for hepatitis B core antibody or hepatitis B surface antigen must have a negative polymerase chain reaction (PCR) result before enrollment, i.e. HBV DNA must be undetectable, provided that they are willing to undergo monthly DNA testing. Those who are PCR positive will be excluded. Patients who are positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
  • Any uncontrolled active systemic infection.
  • Major surgery within 4 weeks of first dose of study drug.
  • Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 2 or higher congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization.
  • Unable to swallow capsules or malabsorption syndrome, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction at time of screening.
  • Breastfeeding or pregnant. Serum pregnancy test will be conducted.
  • Male subject who is considering fathering a child or donating sperm during the study or for approximately 90 days after the last dose of study drugs.
  • Unwilling or unable to participate in all required study evaluations and procedures. Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations)
  • Patients receiving any other study agents
  • Patients with known CNS involvement
  • Baseline QTcF >480 ms. NOTE: This criterion does not apply to patients with a left bundle branch block.
  • Patients who require warfarin or other vitamin K antagonists for anticoagulation (other anticoagulants are allowed).
  • Concurrent administration of medications or foods that are strong inhibitors or inducers of CYP3A (see Appendix B).
  • Patients with ongoing use of prophylactic antibiotics are eligible as long as there is no evidence of active infection and the antibiotic is not a prohibited medication
  • Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV), and herpes zoster (VZV) at start of treatment
  • Significant co-morbid condition or disease which in the judgment of the Principal Investigator would place the patient at undue risk or interfere with the study

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Ohio State University

    Columbus, Ohio, 43210

  • MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Venetoclax Plus Dose-adjusted R-EPOCH or R-CHOP for Richter's Syndrome

This research study is evaluating the combination of a study drug, venetoclax, and a standard chemotherapy regimen, R-EPOCH or R-CHOP, as a possible treatment for Richter's Syndrome.

The drugs involved in this study are:

  • Venetoclax
  • R-EPOCH:
  • Rituximab
  • Etoposide
  • Prednisone
  • Vincristine Sulfate (Oncovin)
  • Cyclophosphamide
  • Doxorubicin Hydrochloride (Hydroxydaunomycin)
  • R-CHOP:
  • Rituximab
  • Cyclophosphamide Vincristine
  • Doxorubicin Hydrochloride (Hydroxydaunomycin)
  • Sulfate (Oncovin)
  • Prednisone
Read the detailed description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.

Tumor cells from patients with Richter's Syndrome are often resistant to chemotherapy. One reason for this may be that a protein called BCL-2 can prevent cancer cells from dying after being exposed to chemotherapy. Venetoclax is an oral drug that specifically targets BCL-2. It has already been shown to be highly effective at killing tumor cells from CLL patients whose cells are resistant to chemotherapy, leading to its FDA (the U.S. Food and Drug Administration) approval for these patients. A small number of patients with Richter's Syndrome have been treated with venetoclax as a single drug, and some of these patients had improvement of their cancer with this treatment.

In this research study, the investigators are looking to see whether adding venetoclax to a standard chemotherapy regimen, R-EPOCH or R-CHOP, will help this chemotherapy work better to more effectively kill tumor cells in patients with Richter's Syndrome. Venetoclax is not approved for Richter's Syndrome or for use in combination with chemotherapy, which is why its use in this trial is considered to be investigational.

Being tested
Venetoclax, DA-EPOCH-R, R-CHOP
Keywords
Richter Syndrome

What participants receive

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

  • VenetoclaxDrug

    Also called Venclexta

    Venetoclax is an Antineoplastic Agent; BCL-2 Inhibitor

  • DA-EPOCH-ROther

    Intensive chemotherapy regiment

  • R-CHOPOther

    Intensive chemotherapy regiment

Study groups in NCT03054896
Study groupRoleWhat they receive
VR-EPOCH (Cohort 1)Experimental* Standard chemotherapy regimen, DA-EPOCH-R * Chemotherapy cycles will be administered approximately every 3 weeks * Initial venetoclax dose ramp-up will be done in a condensed fashion over approximately 5 days, followed by continuous daily dosing of 400mg
Receives: Drug: Venetoclax; Other: DA-EPOCH-R
VR-CHOP (Cohort 2)Experimental* Standard chemotherapy regimen, R-CHOP * Chemotherapy cycles will be administered approximately every 3 weeks * Initial venetoclax dose ramp-up will be done in a condensed fashion over approximately 5 days, followed by continuous daily dosing of 400mg
Receives: Drug: Venetoclax; Other: R-CHOP

What is being measured

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

  1. 3-month Rate of Complete Response (CR)

    The CRR is defined as the proportion of participants achieving complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) based on 2008 IW-CLL Response Criteria.

    Measured: Relevant to this endpoint, it is at 3 month.

Secondary outcomes (2)

  1. Median Progression-Free Survival (PFS)

    Progression-free survival based on the Kaplan-Meier method is defined as the duration between randomization and documented disease progression (PD) or death, or is censored at time of last disease assessment.

    Measured: Patients monitored monthly up to the 1 year mark, after that every 3 months, and response assessments every 6 months. After 2 year, monitored every 3 months and response assessments every 12 months. In long- term follow-up every 6 months up to 5 years.

  2. Median Overall Survival (OS)

    Overall Survival (OS) based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.

    Measured: Up to 5 years

Timeline

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

  1. First posted16 Feb 2017
  2. Study start8 Mar 2017
  3. Primary completion24 Dec 2025
  4. Study completion1 Dec 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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
69 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03054896
Sponsor's protocol ID
16-596
Status last verified
Jun 2026
First submitted
10 Feb 2017
Last updated
10 Jul 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Davids MS, Rogers KA, Tyekucheva S, Wang Z, Pazienza S, Renner SK, Montegaard J, Ihuoma U, Lehmberg TZ, Parry EM, Wu CJ, Jacobson CA, Fisher DC, Thompson PA, Brown JR. Venetoclax plus dose-adjusted R-EPOCH for Richter syndrome. Blood. 2022 Feb 3;139(5):686-689. doi: 10.1182/blood.2021011386.

    PubMed 34788401

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Venetoclax, DA-EPOCH-R and R-CHOP in people with Richter Syndrome, run by Dana-Farber Cancer Institute at 3 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 19 inclusion and 31 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 10 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 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 phase mean?

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 10 Jul 2026). 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?

3-month Rate of Complete Response (CR) (time frame: Relevant to this endpoint, it is at 3 month.). 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 NCT03054896, which also lists 1 linked publication.

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 10 Jul 2026.

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