Promising new combo tackles rare leukemia complication
NCT ID NCT04679012
First seen Jun 25, 2026 · Last updated Jun 27, 2026 · Updated 1 time
Summary
This phase 2 trial is testing whether adding the drug polatuzumab vedotin to standard chemotherapy can improve remission rates in people with Richter's transformation, an aggressive lymphoma that can develop from chronic lymphocytic leukemia (CLL). About 20 adults with confirmed Richter's transformation will receive up to six cycles of the combination therapy. Researchers will track how many achieve complete remission and monitor side effects over about two years.
What this could mean
Our plain-language read of the trial. This is informational only, not medical advice or a prediction.
- Active substance
- Polatuzumab vedotin (Polivy) combined with rituximab, etoposide, prednisone, cyclophosphamide, and hydroxydaunorubicin
- What this could lead to
- If successful, this could offer a more effective treatment option for Richter's transformation, a rare and aggressive complication of chronic lymphocytic leukemia.
- What could go wrong
- This is a small, early-phase (phase 2) study with only 20 participants, so results may not apply broadly. The combination chemotherapy has significant side effects, and the drug may not improve outcomes.
This is an AI summary of the original study and may miss details. Read our disclaimer.
Study facts
What this study's own registry entry says, in plain language.
- Phase
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Phase 2
Tests whether the treatment actually works, and watches for side effects, in a larger group.
- Participants
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About 20 people
The number the study aims to enrol. It can still change while the study runs.
- Started
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Sep 2021
- Expected to finish
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Sep 2027
An estimate. End dates often move.
- Lead sponsor
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Other sponsor
The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.
Who can take part
This study's own entry requirements. Only the study team can say for certain whether you qualify.
- Ages
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18 years and older
- Sex
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Anyone
- Healthy volunteers
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Not accepted
This study is not open to healthy volunteers. The entry requirements below say who it is open to.
Show the full entry requirements Hide the full entry requirements
Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.
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.
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Conditions
The condition(s) this trial relates to.
As listed by the trial registrant
The condition terms exactly as the trial's registrant entered them.
How to take part
Only the study team decides who joins. These are the ways to reach them.
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The places running it
4 sites. The list below names each one and where it is.
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The official record
ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.
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A doctor treating you
A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.
Contacts and locations
Locations
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Columbia University Medical Center
RECRUITINGNew York, New York, 10032, United States
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Mount Sinai- Icahn School of Medicine
RECRUITINGNew York, New York, 10029, United States
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Ohio state University
RECRUITINGColumbus, Ohio, 43210, United States
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Weill Cornell Medicine
RECRUITINGNew York, New York, 10065, United States
More trials for these conditions
Other studies related to the condition(s) this trial covers.
- Two-Drug combo aims to push CLL into deep remission
- Can a new BTK inhibitor outsmart resistance in CLL?
- Can a new pill outsmart Drug-Resistant leukemia?
- Can engineered immune cells beat tough B-Cell cancers?
- Can a targeted drug outperform chemo for a common blood cancer?
- Can a triple drug combo outsmart High-Risk CLL?