Brief Title
Polatuzumab Vedotin in Combination With Chemotherapy in Subjects With Richter's Transformation
Official Title
Phase II Study of Polatuzumab Vedotin in Combination With Chemotherapy in Subjects With Richter's Transformation
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.
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Complete metabolic remission/complete remission (CMR/CR) rate of subjects at end of treatment (EOT)
Secondary Outcome
Safety of polatuzumab vedotin plus infusional chemoimmunotherapy (CIT) containing rituximab, etoposide, prednisone, cyclophosphamide and hydroxydaunorubicin in patients with newly diagnosed Richter's Transformation.
Condition
Richter Syndrome
Intervention
Polatuzumab Vedotin
Study Arms / Comparison Groups
Polatuzumab vedotin plus R-EPCH
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
20
Start Date
September 24, 2021
Completion Date
September 2026
Primary Completion Date
September 2025
Eligibility Criteria
Inclusion Criteria:
- Subject must have confirmed diagnosis of CLL 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 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
- 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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
John Allan, M.D., 2127461362, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT04679012
Organization ID
20-08022533
Responsible Party
Sponsor
Study Sponsor
Weill Medical College of Cornell University
Collaborators
Genentech, Inc.
Study Sponsor
John Allan, M.D., Principal Investigator, Weill Medical College of Cornell University
Verification Date
December 2022