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

NCT03739619 | Completed Phase 1 Results DMC FDA Drug

• 4 other identifiers: IRB00104033NCI-2018-02221Winship4388-18P30CA138292
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Recurrent Hodgkin Lymphoma; Refractory Hodgkin Lymphoma; Classical Hodgkin Lymphoma; Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerable Dose (Phase I)

  Maximum tolerable dose will be defined as the highest dose level where at most 1 of 6 patients experience dose limiting toxicity (DLT).

  Up to completion of course 2 at 42 days after study start

• Complete Response (CR) Rate (Phase II)

  Complete response rate will be determined by dividing the number of CRs (per Lugano criteria) by the total number of evaluable patients.

  Up to 2 years from discontinuation of study therapy

Secondary Outcomes (4)

• Overall Response Rate (Phase II)

  Up to 2 years from discontinuation of study therapy

• Duration of Response (Phase II)

  Up to 2 years from discontinuation of study therapy

• Progression Free Survival (PFS) (Phase II)

  Up to 2 years from discontinuation of study therapy

• Overall Survival (OS) (Phase II)

  Up to 2 years from discontinuation of study therapy

Study Arms (1)

Gemcitabine, bendamustine, nivolumab

EXPERIMENTAL

Patients 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.

Drug: Bendamustine; Drug: Gemcitabine; Biological: Nivolumab

Interventions

Bendamustine DRUG

Given IV

Also known as: Bendamustine Hydrochloride, Cytostasan Hydrochloride, Levact, Ribomustin, SyB L-0501, Treanda

Gemcitabine, bendamustine, nivolumab

Gemcitabine DRUG

Given IV

Also known as: dFdC, dFdCyd, Difluorodeoxycytidine

Gemcitabine, bendamustine, nivolumab

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Gemcitabine, bendamustine, nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead
• Bristol-Myers Squibb: collaborator
• National Cancer Institute (NCI): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (2)

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342, United States

Location

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Bendamustine Hydrochloride; Gemcitabine; Nivolumab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Jonathon Cohen, MD
• Organization: Emory University

jonathon.cohen@emory.edu

404-778-2214

Study Officials

• Jonathon Cohen, MD, MS

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 1, 2018
• First Posted: November 14, 2018
• Study Start: November 26, 2018
• Primary Completion: December 22, 2023
• Study Completion: April 30, 2025
• Last Updated: August 6, 2025
• Results First Posted: August 6, 2025

Record last verified: 2025-07

Locations

US (2)