Clinical Trials /

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

NCT04679012

Description:

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.

Related Conditions:
  • Chronic Lymphocytic Leukemia
  • Richter Syndrome
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: 20-08022533
  • NCT ID: NCT04679012

Conditions

  • Richter Syndrome
  • Chronic Lymphocytic Leukemia

Interventions

DrugSynonymsArms
Polatuzumab VedotinPolivyPolatuzumab vedotin plus R-EPCH
RituximabRituxan, chimeric anti-CD20 monoclonal antibodyPolatuzumab vedotin plus R-EPCH
EtoposideVP-16, VePesid, etopophos, toposarPolatuzumab vedotin plus R-EPCH
PrednisoneDeltasone, Orasone, Paracort, CortanPolatuzumab vedotin plus R-EPCH
CyclophosphamidecytoxanPolatuzumab vedotin plus R-EPCH
HydroxydaunomycinDoxorubicin Hydrochloride, Hydroxydoxorubicin HydrochloridePolatuzumab vedotin plus R-EPCH

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Polatuzumab vedotin plus R-EPCHExperimentalPolatuzumab 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.
  • Polatuzumab Vedotin
  • Rituximab
  • Etoposide
  • Prednisone
  • Cyclophosphamide
  • Hydroxydaunomycin

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete metabolic remission/complete remission (CMR/CR) rate of subjects at end of treatment (EOT)
Time Frame:19 weeks
Safety Issue:
Description:Percentage of subjects who achieve CMR/CR on study.

Secondary Outcome Measures

Measure:Safety of polatuzumab vedotin plus infusional chemoimmunotherapy (CIT) containing rituximab, etoposide, prednisone, cyclophosphamide and hydroxydaunorubicin in patients with newly diagnosed Richter's Transformation.
Time Frame:1.5 years
Safety Issue:
Description:Percentage of subjects who experience 1 or more adverse events.
Measure:Overall response rate (ORR)
Time Frame:1.5 years
Safety Issue:
Description:Rate of subjects who achieve a partial or complete response.
Measure:Progression free survival (PFS)
Time Frame:1.5 years
Safety Issue:
Description:Measured from time of first study drug administration to objective or symptomatic progression or death.
Measure:Overall survival (OS)
Time Frame:1.5 years
Safety Issue:
Description:Measured from time of first study drug administration to death from any cause.
Measure:Allogeneic transplantation rate in eligible patients
Time Frame:1.5 years
Safety Issue:
Description:Percentage of eligible patients able to get allogeneic stem cell transplant.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Weill Medical College of Cornell University

Trial Keywords

  • Polatuzumab vedotin
  • CLL
  • Richter's Transformation

Last Updated

December 22, 2020