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

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04679012
• Other study ID #: 20-08022533
• Status: Recruiting
• Phase: Phase 2
• Start date: September 24, 2021
• Est. completion date: September 2026

Study information

• Verified date: November 2023
• Source: Weill Medical College of Cornell University
• Contact: Amelyn Rodriguez, R.N.
• Phone: 2127461362
• Email: amr2017[@]med.cornell.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: September 2026
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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
• 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.

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Richter Syndrome

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
United States	Ohio state University	Columbus	Ohio
United States	Columbia University Medical Center	New York	New York
United States	Mount Sinai- Icahn School of Medicine	New York	New York
United States	Weill Cornell Medicine	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete metabolic remission/complete remission (CMR/CR) rate of subjects at end of treatment (EOT)	Percentage of subjects who achieve CMR/CR on study.	19 weeks
Secondary	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.	1.5 years
Secondary	Overall response rate (ORR)	Rate of subjects who achieve a partial or complete response.	3 years
Secondary	Progression free survival (PFS)	Measured from time of first study drug administration to objective or symptomatic progression or death.	3 years
Secondary	Overall survival (OS)	Measured from time of first study drug administration to death from any cause.	3 years
Secondary	Allogeneic transplantation rate in eligible patients	Percentage of eligible patients able to get allogeneic stem cell transplant.	3 years

External Links

•   WCM Joint Clinical Trials Office