Clinical Trials /

POLA+BR for Relapsed or Refractory DLBCL

NCT04535102

Description:

This is a phase II multicenter, open-label study of polatuzumab vedotin administered by IV infusion in combination with standard doses of bendamustine (B) and rituximab (R) in transplant-eligible patients with relapsed or refractory DLBCL. A total of 22 patients will be enrolled over a period of 2 years through the University of Colorado and additional study sites if applicable. Study treatment will be given in 21-day cycles for patients with DLBCL.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Diffuse Large B-Cell Lymphoma Activated B-Cell Type
  • Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • Double-Hit Lymphoma
  • EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma
  • HHV8-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • High Grade B-Cell Lymphoma, Not Otherwise Specified
  • Primary Mediastinal B-Cell Lymphoma
  • T-Cell/Histiocyte-Rich Large B-Cell Lymphoma
  • Triple-Hit Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: POLA+BR for Relapsed or Refractory DLBCL
  • Official Title: POLATUZUMAB PLUS BENDAMUSTINE PLUS RITUXIMAB (POLA+BR) AS SALVAGE THERAPY PRIOR TO AUTOLOGOUS STEM CELL TRANSPLANT FOR PATIENTS WITH RELAPSED OR PRIMARY REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA

Clinical Trial IDs

  • ORG STUDY ID: 19-1195.cc
  • SECONDARY ID: P30CA046934
  • NCT ID: NCT04535102

Conditions

  • Diffuse Large B Cell Lymphoma

Interventions

DrugSynonymsArms
Polatuzumab VedotinPolatuzumab + BR (minimum 3 cycles)

Purpose

This is a phase II multicenter, open-label study of polatuzumab vedotin administered by IV infusion in combination with standard doses of bendamustine (B) and rituximab (R) in transplant-eligible patients with relapsed or refractory DLBCL. A total of 22 patients will be enrolled over a period of 2 years through the University of Colorado and additional study sites if applicable. Study treatment will be given in 21-day cycles for patients with DLBCL.

Detailed Description

      The first day of treatment will constitute Cycle 1 Day 1. Patients will be treated with a
      minimum of 3 cycles to upto a maximum six cycles to optimize response prior to ASCT per
      investigator discretion.

      All patients will be evaluated for safety and efficacy according to the schedules of
      assessments.

      All patients will be assessed for response to treatment by the investigator with the use of
      standard criteria according to the Modified Lugano Response Criteria (Cheson et al. 2014; see
      Appendix 3) at screening and at the following timepoints:

        -  At the time of screening

        -  At the time of primary response assessment, 3 weeks after completion of study treatment
           (i.e., 3 weeks after Day 1 of Cycle 3 or after last dose of study medication)) Imaging
           at these timepoints must include FDG-PET (18F-fluorodeoxyglucose-positron emission
           tomography) and a diagnostic-quality CT scan with both oral and IV contrast. A combined
           PET/CT scan is encouraged if feasible. CT scans with oral and IV contrast should include
           neck, chest, abdomen, and pelvic scans. In patients for whom contrast is
           contraindicated, (e.g., patients with contrast allergy or impaired renal clearance or
           patient denial), PET-CT scans without contrast are permitted so long as they permit
           consistent and precise measurement of target lesions during the study treatment period.

      Patients will also be evaluated every 3 months for 2 years, or until disease progression,
      death, withdrawal of consent, or initiation of another anti-cancer therapy. Tumor assessments
      should also be performed to confirm clinical suspicion of relapse or disease progression for
      documentation. The study will end when all patients enrolled have been followed until death,
      have withdrawn consent, have been lost to follow-up, until 2-year follow up, or the Sponsor
      decides to end the trial, whichever occurs first.

      Once the last patient enrolls and undergoes EOT PET-CT assessment, primary endpoint data and
      interim survival analysis will be evaluated and published/presented at meetings. Subsequent
      survival analysis will be published post 2-yr follow-up
    

Trial Arms

NameTypeDescriptionInterventions
Polatuzumab + BR (minimum 3 cycles)ExperimentalPatients will be treated with a minimum of 3 cycles up to a maximum six cycles to optimize response prior to ASCT (stem cell transplant) per investigator discretion
  • Polatuzumab Vedotin

Eligibility Criteria

        Inclusion Criteria:

          1. Signed ICF

          2. Age ≥ 18 years

          3. Able to comply with the study protocol, in the investigator's judgment

          4. Histologically confirmed DLBCL (Obtaining pathology samples is not required prior to
             enrollment, but confirmation of availability is required prior to enrollment)

          5. Must have received at least one prior rituximab containing chemotherapy therapy for
             DLBCL.

          6. Patients must be transplant-eligible and have either relapsed or have become
             refractory to a prior regimen.

          7. The following DLBCL histologies would be considered eligible for study entry:

             - DLBCL, not otherwise specified (NOS) (including both GCB type and ABC type)

             - T-cell/histiocyte-rich large B-cell lymphoma

               -  High-grade B-cell lymphoma with MYC and BCL-2 and/or BCL-6 rearrangements

               -  High grade B-cell lymphoma, NOS

               -  Primary mediastinal (thymic) large B-cell lymphoma

               -  Epstein Barr virus positive DLBCL, NOS

               -  HHV8-positive DLBCL, NOS

               -  HIV positive DLBCL

          8. At least one bi-dimensionally measurable lesion on imaging scan defined as > 1.5 cm in
             its longest dimension

          9. Life expectancy of at least 24 weeks

         10. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2

         11. Adequate hematologic function unless inadequate function is due to underlying disease,
             such as extensive bone marrow involvement or hypersplenism secondary to the
             involvement of the spleen by lymphoma per the investigator. Adequate hematologic
             function is defined as follows:

             - Hemoglobin ≥ 9 g/dL o ANC ≥ 1.0 x 109/L

             - Platelet count ≥ 75 x 109/L

         12. For women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea
             and age > 45 years) or surgically sterile (absence of ovaries and/or uterus):

             agreement to remain abstinent or to use single highly effective or combined
             contraceptive methods that result in a failure rate of < 1% per year during the
             treatment period and for ≥ 12 months after the last dose of rituximab.

               -  Abstinence is only acceptable if it is in line with the preferred and usual
                  lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation,
                  symptothermal, or post-ovulation methods) and withdrawal are not acceptable
                  methods of contraception.

               -  Examples of highly effective contraceptive methods with a failure rate of < 1%
                  per year include tubal ligation, male sterilization, hormonal implants,
                  established, proper use of combined oral or injected hormonal contraceptives, and
                  certain intrauterine devices. Alternatively, two methods (e.g., two barrier
                  methods such as a condom and a cervical cap) may be combined to achieve a failure
                  rate of < 1% per year. Barrier methods must always be supplemented with the use
                  of a spermicide.

         13. For women of childbearing potential, a negative serum pregnancy test result within 7
             days prior to commencement of dosing. Women who are considered not to be of
             childbearing potential are not required to have a pregnancy test.

         14. For men, agreement to remain abstinent or to use a condom plus an additional
             contraceptive method that together result in a failure rate of < 1% per year during
             the treatment period and for at least 6 months after the last dose of study drug and
             agreement to refrain from donating sperm during this same period.

               -  Men with a pregnant partner must agree to remain abstinent or to use a condom for
                  the duration of the pregnancy.

               -  Abstinence is only acceptable if it is in line with the preferred and usual
                  lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation,
                  symptothermal, or post-ovulation methods) and withdrawal are not acceptable
                  methods of contraception.

               -  Male patients considering preservation of fertility should bank sperm before
                  treatment with polatuzumab vedotin.

        Exclusion Criteria:

          1. History of severe allergic or anaphylactic reactions to humanized or murine MAbs (or
             recombinant antibody-related fusion proteins) or known sensitivity or allergy to
             murine products

          2. Contraindication to bendamustine or rituximab.

          3. History of sensitivity to mannitol (mannitol is an excipient in bendamustine).

          4. Prior use of any monoclonal antibody (MAb), radioimmunoconjugate, or antibody drug
             conjugate (ADC) within 5 half-lives or 4 weeks, whichever is longer, before Cycle 1
             Day 1.

          5. Treatment with chemotherapy, immunotherapy, immunosuppressive therapy, or any
             investigational agent for the purposes of treating cancer within 2 weeks prior to
             Cycle 1 Day 1. Radiotherapy for palliative relief of symptoms is allowed.

          6. All acute, clinically significant treatment-related toxicity from prior therapy,
             except for alopecia, must have resolved to Grade ≤ 2 prior to Cycle 1 Day 1.

          7. Ongoing corticosteroid use > 30 mg/day prednisone or equivalent, for purposes other
             than lymphoma symptom control. Patients receiving corticosteroid treatment ≤ 30 mg/day
             prednisone or equivalent must be documented to be on a stable dose prior to study
             enrollment and initiation of therapy (Cycle 1 Day 1).

          8. Ineligibility for ASCT (determined by investigator per local institutional practice)

          9. Prior ASCT

         10. History of transformation of indolent disease to DLBCL

         11. Active CNS lymphoma. (Previously treated CNS disease is allowed)

         12. Current Grade > 1 peripheral neuropathy

         13. History of other malignancy that could affect compliance with the protocol or
             interpretation of results. Exceptions include, but are not limited to:

             • Patients with a history of curatively treated basal or squamous cell carcinoma of
             the skin or in situ carcinoma of the cervix or ductal carcinoma in situ of the breast
             at any time prior to the study are eligible.

             • A patient with any other malignancy that has been treated with curative intent and
             the malignancy has been in remission without treatment for > 3 years prior to
             enrollment is eligible.

             • Patients with low-grade, early-stage prostate cancer with no requirement for
             systemic therapy at any time prior to study are eligible.

         14. Evidence of significant, uncontrolled concomitant diseases that could affect
             compliance with the protocol or interpretation of results, including significant
             cardiovascular disease (such as New York Heart Association Class III or IV cardiac
             disease, myocardial infarction within the last 6 months, unstable arrhythmias, or
             unstable angina) or significant pulmonary disease (including obstructive pulmonary
             disease and history of bronchospasm).

         15. 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 (IV) antibiotics or hospitalization
             (relating to the completion of the course of antibiotics) within 4 weeks prior to
             Cycle 1 Day 1.

         16. Patients with suspected or latent tuberculosis.

             • Latent tuberculosis should be confirmed according to local testing requirements.

         17. Positive test results for chronic hepatitis B virus (HBV) infection (defined as
             positive hepatitis B surface antigen [HBsAg] serology).

             • Patients with occult or prior HBV infection (defined as negative HBsAg and positive
             hepatitis B core antibody [HBcAb]) may be included if HBV DNA is undetectable,
             provided that they are willing to undergo DNA testing on day 1 of every cycle and
             monthly for at least 12 months after the last cycle of study treatment and are willing
             to get prophylaxis with lamuvidine or entecavir for 6 months post immunosuppressive
             therapy. Patients who have protective titers of hepatitis B surface antibody (HBsAb)
             after vaccination or prior but cured hepatitis B are eligible.

         18. Patients who are positive for Hepatitis C virus (HCV) antibody are eligible only if
             PCR is negative for HCV RNA.

         19. Positive test results for uncontrolled HIV infection. • For patients with controlled
             HIV status (Positive HIV antibody, on Antiretroviral therapy with stable HIV viral
             load) are eligible.

         20. Known infection human T-cell leukemia virus 1 (HTLV-1) virus. 21. Vaccination with a
             live vaccine within 28 days prior to treatment.

        22. Recent major surgery (within 6 weeks before the start of Cycle 1 Day 1) other than for
        diagnosis.

        23. Women who are pregnant or lactating or who intend to become pregnant within a year of
        the last dose of study treatment in the rituximab cohorts or within 18 months of the last
        dose of study treatment in the obinutuzumab cohort

        24. Any of the following abnormal laboratory values, unless abnormal laboratory values are
        due to underlying lymphoma per the investigator:

        • Creatinine > 1.5 x upper limit of normal (ULN) or a measured creatinine clearance < 40
        mL/min • AST or ALT > 2.5 x ULN

          -  Total bilirubin ≥ 1.5 x ULN. Patients with documented Gilbert disease may be enrolled
             if total bilirubin is ≤ 3 x ULN

          -  INR or PT > 1.5 x ULN in the absence of therapeutic anticoagulation

          -  PTT or aPTT > 1.5 x ULN in the absence of a lupus anticoagulant

             25. Any other diseases, metabolic dysfunction, physical examination finding, or
             clinical laboratory finding giving reasonable suspicion of a disease or condition that
             contraindicates the use of an investigational drug or that may affect the
             interpretation of the results or render the patient at high risk from treatment
             complications
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete response at primary response
Time Frame:3 weeks after last dose of study medication
Safety Issue:
Description:The assessment is based on PET/CT, as determined by the investigator

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Colorado, Denver

Last Updated

August 31, 2020