Clinical Trials /

Gemcitabine, Bendamustine, and Nivolumab in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma

NCT03739619

Description:

This phase I/II trial studies the side effects and best dose of gemcitabine, bendamustine, and nivolumab when given together and to see how well they work in treating patients with classic Hodgkin lymphoma that has come back or does not respond to treatment. Drugs used in chemotherapy, such as gemcitabine and bendamustine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving gemcitabine, bendamustine, and nivolumab may work better in treating patients with classic Hodgkin lymphoma.

Related Conditions:
  • Classical Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Gemcitabine, Bendamustine, and Nivolumab in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma
  • Official Title: A Phase I/II Study of Gemcitabine, Bendamustine, and Nivolumab in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: IRB00104033
  • SECONDARY ID: NCI-2018-02221
  • SECONDARY ID: Winship4388-18
  • NCT ID: NCT03739619

Conditions

  • Recurrent Hodgkin Lymphoma
  • Refractory Hodgkin Lymphoma
  • Classical Hodgkin Lymphoma
  • Hodgkin Lymphoma

Interventions

DrugSynonymsArms
BendamustineBendamustine Hydrochloride, Cytostasan Hydrochloride, Levact, Ribomustin, SyB L-0501, TreandaGemcitabine, bendamustine, nivolumab
GemcitabinedFdC, dFdCyd, DifluorodeoxycytidineGemcitabine, bendamustine, nivolumab
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoGemcitabine, bendamustine, nivolumab

Purpose

This phase I/II trial studies the side effects and best dose of gemcitabine, bendamustine, and nivolumab when given together and to see how well they work in treating patients with classic Hodgkin lymphoma that has come back or does not respond to treatment. Drugs used in chemotherapy, such as gemcitabine and bendamustine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving gemcitabine, bendamustine, and nivolumab may work better in treating patients with classic Hodgkin lymphoma.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate the toxicity and determine the maximum tolerated dose (MTD) of combined
      gemcitabine, bendamustine, and nivolumab in patients with relapsed/refractory classical
      Hodgkin lymphoma.

      II. To determine the efficacy of bendamustine, gemcitabine, and nivolumab in patients with
      relapsed/refractory classical Hodgkin lymphoma.

      SECONDARY OBJECTIVES:

      I. To evaluate the duration of response, progression-free survival, and overall survival for
      patients with relapsed/refractory classical Hodgkin lymphoma who receive gemcitabine,
      bendamustine, and nivolumab, including those who receive nivolumab maintenance.

      OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

      Patients receive gemcitabine intravenously (IV) over 30 minutes on day 1, bendamustine IV
      over 30 minutes on days 1 and 2, and nivolumab over 60 minutes IV on day 1. Treatment repeats
      every 21 days for up to 6 courses in the absence of disease progression or unacceptable
      toxicity. Patients may then receive nivolumab IV over 60 minutes on day 1. Treatment with
      single agent nivolumab repeats every 28 days for up to 26 courses in the absence of disease
      progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months for 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Gemcitabine, bendamustine, nivolumabExperimentalPatients receive gemcitabine IV over 30 minutes on day 1, bendamustine IV over 30 minutes on days 1 and 2, and nivolumab over 60 minutes IV on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may then receive nivolumab IV over 60 minutes on day 1. Treatment with single agent nivolumab repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
  • Bendamustine
  • Gemcitabine
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically documented classical Hodgkin lymphoma that is recurrent or refractory
             after standard chemotherapy. Core biopsies are acceptable if they contain adequate
             tissue for primary diagnosis and immunophenotyping. Bone marrow biopsies as the sole
             means of diagnosis are not acceptable. At least one biopsy-proven relapse is required
             for enrollment, but patients who have multiply relapsed disease do not require repeat
             biopsy if not clinically indicated

          -  Prior treatment: patients must have relapsed or progressed after at least one prior
             therapy

               -  Patients with relapsed or refractory disease following autologous stem cell
                  transplantation are permitted. Due to the risk of treatment-refractory graft
                  versus host disease (GVHD), patients who have previously completed an allogeneic
                  transplant are excluded.

               -  Patients may have received gemcitabine, bendamustine, or nivolumab in the past
                  but may not have discontinued therapy due to toxicity felt to be related to that
                  specific drug

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          -  Measurable disease must be present either on physical examination or imaging studies.
             Non-measurable disease alone is not acceptable

               -  Measurable disease

                    -  Lesions that can be accurately measured in at least two dimensions as ≥ 1.0
                       x 1.0 cm by computerized tomography (CT), positron emission tomography
                       (PET)/CT (positron emission tomography/CT), or magnetic resonance imaging
                       (MRI).

                    -  If identified by PET/CT, there must be at least one lesion that demonstrates
                       abnormal fludeoxyglucose (FDG) avidity, consistent with active disease.
                       Ultrasound or physical examination alone may not be utilized to confirm
                       measurable disease

               -  Non-measurable disease

                    -  All other lesions, including small lesions (less than 1.0 x 1.0 cm) and
                       truly non-measurable lesions

                    -  Lesions that are considered non-measurable include the following:

                         -  Bone lesions (lesions if present should be noted)

                         -  Ascites

                         -  Pleural/pericardial effusion

                         -  Lymphangitis cutis/pulmonis

                         -  Bone marrow (involvement by Hodgkin lymphoma should be noted)

          -  Non-pregnant and non-nursing. Women and men of reproductive potential should agree to
             use an effective means of birth control

          -  Patients with human immunodeficiency virus (HIV) infection are eligible. Patients with
             HIV infection must meet the following: no evidence of co-infection with hepatitis B or
             C; cluster of differentiation 4+ (CD4+) count ≥ 400/mm; no evidence of resistant
             strains of HIV; on anti-HIV therapy with an HIV viral load < 50 copies HIV ribonucleic
             acid (RNA)/mL. Patients with HIV must have ongoing follow-up with an infectious
             disease specialist and must have been evaluated within 90 days of cycle 1 day 1

          -  Patients with a history of hepatitis C are eligible as long as the hepatitis C has
             been treated and cleared and they have no evidence of hepatic dysfunction related to
             hepatitis C. Patients must have been seen by a hepatologist within 6 months of cycle 1
             day 1

          -  Patients who test positive for hepatitis B core antibody may enroll on the study as
             long as they test negative for both hepatitis B surface antigen and hepatitis B
             deoxyribonucleic acid (DNA), and if they have no evidence of hepatic dysfunction that
             is felt to be related to hepatitis B

          -  Patients must have adequate pulmonary function, defined as the following:

               -  No history of drug-related, radiation-induced, or autoimmune pneumonitis
                  requiring hospital admission

               -  Baseline pulse oximetry reading of ≥ 92% on room air

               -  Patients with a history of asthma or chronic obstructive pulmonary disease (COPD)
                  must have no oxygen requirement, must have not had a hospital admission for
                  COPD/asthma exacerbation within the past 2 years, and must not have received
                  systemic steroids (≥ 10 mg prednisone for more than 7 days) for asthma/COPD
                  within the past 2 years

          -  Patients with hypothyroidism or type 1 diabetes mellitus that are on chronic hormonal
             therapy and which are well-controlled are eligible

          -  Granulocytes ≥ 1000/µl

          -  Platelet count ≥ 75,000/µl

          -  Creatinine clearance ≥ 50 mL/min

          -  Bilirubin ≤ 2.0 mg/dL

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.0 x upper limits
             of normal

        Exclusion Criteria:

          -  Due to the teratogenic potential of these agents, pregnant or nursing patients may not
             be enrolled

          -  Patients may not have an auto-immune disease requiring systemic immunosuppression,
             biologic therapy, and/or steroid use (≥ 10 mg daily of prednisone or equivalent)

          -  Patients with current or prior central nervous system (CNS) involvement with lymphoma
             are not eligible
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerable dose (Phase I)
Time Frame:Up to completion of course 2 at 42 days after study start
Safety Issue:
Description:Maximum tolerable dose will be defined as the highest dose level where at most 1 of 6 patients experience dose limiting toxicity (DLT).

Secondary Outcome Measures

Measure:Overall response rate (Phase II)
Time Frame:Up to 2 years from discontinuation of study therapy
Safety Issue:
Description:Overall response rate will be evaluated using Lugano criteria of response. Overall response rate will be defined as the total number of patients achieving a partial response or CR as best response through cycle 6 divided by total number of patients treated.
Measure:Duration of response (Phase II)
Time Frame:Up to 2 years from discontinuation of study therapy
Safety Issue:
Description:Duration of response will be evaluated using Lugano criteria of response and will be determined from date of best response to progression or death.
Measure:Progression free survival (PFS) (Phase II)
Time Frame:Up to 2 years from discontinuation of study therapy
Safety Issue:
Description:Progression free survival will be evaluated using Lugano criteria and will be determined from date of first dose of study drug to progression or death.
Measure:Overall survival (OS) (Phase II)
Time Frame:Up to 2 years from discontinuation of study therapy
Safety Issue:
Description:Overall survival will be evaluated using Lugano criteria and will be determined from date of first dose of study drug to death from any cause.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Emory University

Last Updated

June 27, 2019