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

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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

June 2024

Primary Completion Date

December 2023

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 2021