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Richter SyndromePhase 2NCT04679012

Polatuzumab Vedotin in Combination With Chemotherapy in Subjects With Richter's Transformation

A Phase 2 study testing Polatuzumab Vedotin, Rituximab and Etoposide in people with Richter Syndrome and Chronic Lymphocytic Leukemia, run by Weill Medical College of Cornell University at 4 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 study evaluates the effectiveness and safety of Polatuzumab vedotin plus infusional chemoimmunotherapy containing rituximab, etoposide, prednisone, cyclophosphamide and hydroxydaunorubicin. This is a single arm study. Enrolled patients will receive up to six cycles (21-day cycles) of therapy. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Polatuzumab Vedotin, Rituximab and Etoposide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
4 sitesUnited States
Study dates
24 Sep 2021to Sep 2027
Phase
Phase 2
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

  • Subject must have confirmed diagnosis of CLL or small lymphocytic lymphoma (SLL) based upon 2018 International Workshop on CLL (IwCLL) criteria, with biopsy proven Richter's Transformation to a DLBCL subtype.
  • Subject must be ≥18 years of age.
  • Subject must be able to sign informed consent
  • Ability and willingness to comply with the study protocol procedures
  • Life expectancy of at least 24 weeks
  • Subject must have an Eastern Cooperative Oncology Group performance status of ≤2.
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  • Subject must have measurable disease with atleast on LN>- 1.5cm in longest diameter
  • Subject must have adequate bone marrow function and meet the below thresholds prior to treatment.
  • Absolute neutrophil count of ≥1000 cell/uL
  • Hemoglobin ≥ 7 g/dL
  • Platelet count ≥ 30,000 cells/uL- Subjects may receive growth factor or transfusion support no less than 7 days prior to enrollment or C1 D1.
  • Subject must have adequate organ function and meet the thresholds below:
  • Total bilirubin ≤ 1.5 times the upper limit of normal (ULN). Subjects with Gilbert's disease will be granted exception to this rule.
  • Creatinine clearance >30 ml/min/1.73m2 as calculated by the MDRD equation.
  • Ejection fraction ≥ 50% measured by transthoracic echocardiogram or MUGA scan
  • For women of childbearing potential: agreement to remain abstinent or use of contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 12 months after the last dose of study drug.
  • A woman is considered to be of childbearing potential if she is post-menarcheal, has not reached a postmenopausal state (i.e. ≥ 12 months of amenorrhea with no identified cause other than menopause) and has not undergone surgical sterilization (removal of ovaries and or uterus)
  • Acceptable forms of contraception are bilateral tubal ligation, male sterilization, or copper intrauterine devices.
  • For women considered to have childbearing potential a negative serum pregnancy test within 7 days prior to study enrollment and dosing is required.
  • For men, agreement to remain abstinent, or to use a condom plus an additional contraceptive method during the treatment period and for at least 5 months after the last dose of study drug.
  • Men must agree not to donate sperm during that period of time. Male patients interested in preservation of fertility should be advised to sperm bank prior to enrollment and treatment initiation.

Who cannot join

  • Diagnosis of Richter's Transformation not of DLBCL subtype (including but not limited to Hodgkin lymphoma, PLL)
  • Prior therapy targeting Richter's transformation.
  • Any subject that initiates a targeted agent such as BTKi, venetoclax, or PI3K prior to enrollment (Continuation of a targeted CLL directed therapy such as a BTKi, venetoclax, or PI3K will be permitted as a bridge through screening but add on therapies or change in therapy will be exclusionary. These continuation therapies will be permitted up 72 hours prior to study initiation. Bridging therapy with steroid up to equivalent of 40mg of Dexamethasone daily will be allowed prior to study treatment and can be continued up to 24 hours prior to study treatment)
  • Subject has undergone an allogeneic stem cell transplant for CLL within 6 months of study entry.
  • Subject has an active or presumed secondary malignancy at time of enrollment. A subject will be eligible if a previous malignancy was treated with curative intent and there is no evidence of disease recurrence for the past 3 years. Non-melanomatous and cervical squamous cell cancers are an exception and if excised will be allowed to enroll regardless of timing of excision.
  • Subject is known to be positive for HIV.
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  • Active hepatitis C or hepatitis B defined by positive PCRs for viral DNA/RNA. Subjects with a positive Hep B core antibody and negative PCR, are allowed to enroll (prophylaxis is strongly encouraged and monthly monitoring of Hep B PCR is mandatory).
  • Subject has baseline ≥ Grade 2 or greater peripheral neuropathy.
  • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
  • Clinical evidence or known central nervous system involvement with transformed large cells
  • Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
  • Significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, congestive heart failure, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina)
  • 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 intravenous antibiotics or hospitalization within 4 weeks before Cycle 1 day 1.
  • Major surgery within 4 weeks before the start of Cycle 1 day 1. Superficial lymph node biopsies or laprascopic lymph node biopsies are exclusionary to this rule.
  • Pregnant or breastfeeding

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Ohio State University

    Columbus, Ohio, 43210

  • Mount Sinai- Icahn School of Medicine

    New York, New York, 10029

  • Columbia University Medical Center

    New York, New York, 10032

  • Weill Cornell Medicine

    New York, New York, 10065

Other trials in United States

About this study

Official title: Phase II Study of Polatuzumab Vedotin in Combination With Chemotherapy in Subjects With Richter's Transformation

This study evaluates the effectiveness and safety of Polatuzumab vedotin plus infusional chemoimmunotherapy containing rituximab, etoposide, prednisone, cyclophosphamide and hydroxydaunorubicin. This is a single arm study. Enrolled patients will receive up to six cycles (21-day cycles) of therapy. While on study, subjects will be monitored weekly until end of treatment, then followed for 52 weeks or until disease progression or discontinuation due to toxicity or death. After completion of the 52-week follow-up/End of study visit, Subjects will be followed for an additional 104 week period, with an assessment occurring every 12 weeks to evaluate survival outcomes and next line of treatments only.

Read the detailed description

This is an open label, single arm, phase II investigator initiated clinical trial, evaluating efficacy and safety of Polatuzumab vedotin added to a modified infusional dose adjusted R-EPOCH like regimen, given on an inpatient basis, every 21 days, in subjects with Richter's Transformation.

Being tested
Polatuzumab Vedotin, Rituximab, Etoposide, Prednisone, Cyclophosphamide
Keywords
Polatuzumab vedotin, CLL, Richter's Transformation
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

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

  • Polatuzumab VedotinDrug

    Also called Polivy

    Polatuzumab vedotin will be administered as an IV infusion at 1.8mg/kg on Day 1 of each cycle, every 21 days.

  • RituximabDrug

    Also called Rituxan, chimeric anti-CD20 monoclonal antibody

    Rituximab will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. The drug will be given by IV route.

  • EtoposideDrug

    Also called VP-16, VePesid, etopophos, toposar

    Etoposide will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. The drug will be given by IV route.

  • PrednisoneDrug

    Also called Deltasone, Orasone, Paracort, Cortan

    Prednisone will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. Prednisone will be given orally.

  • CyclophosphamideDrug

    Also called cytoxan

    Cyclophosphamide will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. The drug will be given by IV route.

  • HydroxydaunomycinDrug

    Also called Doxorubicin Hydrochloride, Hydroxydoxorubicin Hydrochloride

    Hydroxydaunomycin will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. The drug will be given by IV route.

Study groups in NCT04679012
Study groupRoleWhat they receive
Polatuzumab vedotin plus R-EPCHExperimentalPolatuzumab vedotin will be given in conjunction with 6 cycles of R-EPCH (rituximab, etoposide, prednisone, cyclophosphamide, hydroxydaunorubicin). The dosing schedule and regimen for R-EPCH will follow established protocols. Polatuzumab vedotin will be administered on Day 1 of each 21-day cycle.
Receives: Drug: Polatuzumab Vedotin; Drug: Rituximab; Drug: Etoposide; Drug: Prednisone; Drug: Cyclophosphamide; Drug: Hydroxydaunomycin

What is being measured

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

  1. Complete metabolic remission/complete remission (CMR/CR) rate of subjects at end of treatment (EOT)

    Percentage of subjects who achieve CMR/CR on study.

    Measured: 19 weeks

Secondary outcomes (5)

  1. Safety of polatuzumab vedotin plus infusional chemoimmunotherapy (CIT) containing rituximab, etoposide, prednisone, cyclophosphamide and hydroxydaunorubicin in patients with newly diagnosed Richter's Transformation.

    Percentage of subjects who experience 1 or more adverse events.

    Measured: 1.5 years

  2. Overall response rate (ORR)

    Rate of subjects who achieve a partial or complete response.

    Measured: 3 years

  3. Progression free survival (PFS)

    Measured from time of first study drug administration to objective or symptomatic progression or death.

    Measured: 3 years

  4. Overall survival (OS)

    Measured from time of first study drug administration to death from any cause.

    Measured: 3 years

  5. Allogeneic transplantation rate in eligible patients

    Percentage of eligible patients able to get allogeneic stem cell transplant.

    Measured: 3 years

Timeline

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

  1. First posted22 Dec 2020
  2. Study start24 Sep 2021
  3. Primary completionJan 2027 (estimated)
  4. Study completionSep 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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04679012
Sponsor's protocol ID
20-08022533
Status last verified
Sep 2026
First submitted
16 Dec 2020
Last updated
25 Sep 2026
Results posted
No
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 2 study testing Polatuzumab Vedotin, Rituximab and Etoposide in people with Richter Syndrome and Chronic Lymphocytic Leukemia, run by Weill Medical College of Cornell University 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 21 inclusion and 15 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 25 Sep 2026. 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 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?

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?

Complete metabolic remission/complete remission (CMR/CR) rate of subjects at end of treatment (EOT) (time frame: 19 weeks). 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 NCT04679012.

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 25 Sep 2026.

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