Recruiting
Phase 2

Polatuzumab Vedotin & Chemotherapy

Sponsor:

Weill Medical College of Cornell University

Code:

NCT04679012

Conditions

Richter Syndrome

Chronic Lymphocytic Leukemia

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Polatuzumab Vedotin

Rituximab

Etoposide

Prednisone

Cyclophosphamide

Study Details

Brief 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. 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.

Conditions

Richter Syndrome

Chronic Lymphocytic Leukemia

Study ID

NCT04679012

Start date

Sep 24, 2021

Status verified date

Oct, 2025

Completion date

Sep, 2027

Anticipated

Primary completion date

Sep, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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.
  • 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.

Exclusion Criteria:

  • 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.
  • 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.

Study Design

Enrollment

20 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Polatuzumab vedotin plus R-EPCH

Polatuzumab 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.

Interventions

Polatuzumab Vedotin

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

Rituximab

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.

Etoposide

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.

Prednisone

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.

Cyclophosphamide

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.

Hydroxydaunomycin

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.

Primary outcome measure

  • Complete metabolic remission/complete remission (CMR/CR) rate of subjects at end of treatment (EOT) [ Time Frame: 19 weeks ]

Central Contacts and Locations

Central contacts

Amelyn Rodriguez, R.N.

2127461362amr2017@med.cornell.edu

Katherine Greig, R.N.

2127466738kag9156@med.cornell.edu

Locations

Mount Sinai- Icahn School of Medicine

Recruiting

New York, New York, United States, 10029

Principal Investigator:

Suchitra Sundaram, MD

Columbia University Medical Center

Recruiting

New York, New York, United States, 10032

Principal Investigator:

Andrew Lipsky, MD

Weill Cornell Medicine

Recruiting

New York, New York, United States, 10065

Contacts

Amelyn Rodriguez, R.N.

2127461362amr2017@med.cornell.edu

Katherine Greig, R.N.

2127466738kag9156@med.cornell.edu

Principal Investigator:

John Allan, M.D.

Ohio state University

Recruiting

Columbus, Ohio, United States, 43210

Principal Investigator:

Adam Kittai, MD

More Information

Sponsor

Weill Medical College of Cornell University

Last update posted

Oct 7, 2025

Last verified

Oct, 2025

Keywords

  • Polatuzumab vedotin
  • CLL
  • Richter's Transformation

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Weill Medical College of Cornell University on 2025-10-07.