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Gemcitabine and Bendamustine in Patients With Relapsed or Refractory Hodgkin's Lymphoma

Primary Purpose

Adult Lymphocyte Depletion Hodgkin Lymphoma, Adult Lymphocyte Predominant Hodgkin Lymphoma, Adult Mixed Cellularity Hodgkin Lymphoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
gemcitabine hydrochloride
bendamustine hydrochloride
Sponsored by
Beth Christian
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Lymphocyte Depletion Hodgkin Lymphoma focused on measuring Hodgkin's Lymphoma, relapsed, refractory

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically documented Classical Hodgkin's 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

  • Patients with Hodgkin's lymphoma may have one of the following World Health Organization subtypes:

    • Nodular sclerosis Hodgkin's lymphoma
    • Lymphocyte-rich Hodgkin's lymphoma
    • Mixed cellularity Hodgkin's lymphoma
    • Lymphocyte depletion Hodgkin's lymphoma
    • Nodular lymphocyte predominant Hodgkin's lymphoma
  • Patients must have relapsed or progressed after at least one prior therapy
  • Patients with relapsed or refractory disease following stem cell transplantation are permitted
  • No prior treatment with bendamustine; prior therapy with gemcitabine is permitted
  • 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), PET/CT (positron emission tomography/CT), or magnetic resonance imaging (MRI)

  • 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's lymphoma should be noted)
  • Non-pregnant and non-nursing; due to the teratogenic potential of these agents, pregnant or nursing patients may not be enrolled; 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 (CD)4+ 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; no history of acquired immune deficiency syndrome (AIDS) defining conditions

    • Granulocytes >= 1000/μl
    • Platelet count >= 75,000/μl
    • Creatinine =< 20 mg/dL
    • Bilirubin =< 2.0 mg/dL
    • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.0 x upper limits of normal

Sites / Locations

  • Emory University
  • Ohio State University Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (combination chemotherapy)

Arm Description

Patients receive gemcitabine hydrochloride IV over 30 minutes on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1 and 2. Treatment repeats every 21-28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Adverse Events in Terms of Dose-limiting Toxicity (DLT) and MTD of Bendamustine Hydrochloride (Phase I)
Dose limiting toxicity will be defined during cycle 1 only of the phase I trial. Hematologic and Infectious Dose Limiting Toxicities include: Grade 3 febrile neutropenia persisting> 7 days, Grade 4 infection or febrile neutropenia. Treatment delay>14 days due to grade 3-4 neutropenia or thrombocytopenia. Non-Hematological Dose Limiting Toxicities include: any Grade 3 or 4 non-hematologic toxicity related to study treatment with the exception of nausea or vomiting, alopecia, or electrolyte/glucose abnormalities that are correctable within 72 hours.

Secondary Outcome Measures

Overall Response Rate (ORR) of Bendamustine Hydrochloride and Gemcitabine Hydrochloride in Patients With Relapsed or Refractory Hodgkin Lymphoma (Phase II)
Tested using Simon's two-stage Minimax design. Descriptive statistics (i.e. means, standard deviations, 95% confidence intervals for continuous variables, and frequencies for discrete data) and graphical analyses will be used for all correlative laboratory parameters. The associations between correlative laboratory parameters and clinical response will be evaluated using two sample t test or Fisher's exact test, whichever is appropriate.

Full Information

First Posted
February 6, 2012
Last Updated
October 21, 2021
Sponsor
Beth Christian
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1. Study Identification

Unique Protocol Identification Number
NCT01535924
Brief Title
Gemcitabine and Bendamustine in Patients With Relapsed or Refractory Hodgkin's Lymphoma
Official Title
A Phase I/II Study Of Gemcitabine And Bendamustine In Patients With Relapsed Or Refractory Hodgkin's Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
February 9, 2012 (Actual)
Primary Completion Date
February 20, 2019 (Actual)
Study Completion Date
February 20, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Beth Christian

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase I/II trial studies the side effects and best dose of bendamustine hydrochloride when given together with gemcitabine hydrochloride and to see how well it works in treating patients with relapsed or refractory Hodgkin lymphoma. Drugs used in chemotherapy, such as gemcitabine hydrochloride and bendamustine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug, combination chemotherapy, may kill more cancer cells.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the toxicity and determine the maximum tolerated dose (MTD) of combined bendamustine (bendamustine hydrochloride) and gemcitabine (gemcitabine hydrochloride) in patients with relapsed or refractory Hodgkin's lymphoma. II. To determine the overall response rate of bendamustine and gemcitabine in patients with relapsed and refractory Hodgkin's lymphoma. SECONDARY OBJECTIVES: I. To determine whether therapy with bendamustine in the setting of relapsed or refractory Hodgkin's lymphoma will impact future stem cell collection. OUTLINE: This is a phase I, dose-escalation study of bendamustine hydrochloride followed by a phase II study. Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1 and 2. Treatment repeats every 21-28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3-6 months for 2 years, then every 6 months for up to 3 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Lymphocyte Depletion Hodgkin Lymphoma, Adult Lymphocyte Predominant Hodgkin Lymphoma, Adult Mixed Cellularity Hodgkin Lymphoma, Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma, Adult Nodular Sclerosis Hodgkin Lymphoma, Recurrent Adult Hodgkin Lymphoma
Keywords
Hodgkin's Lymphoma, relapsed, refractory

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
26 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (combination chemotherapy)
Arm Type
Experimental
Arm Description
Patients receive gemcitabine hydrochloride IV over 30 minutes on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1 and 2. Treatment repeats every 21-28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
gemcitabine hydrochloride
Other Intervention Name(s)
dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
bendamustine hydrochloride
Other Intervention Name(s)
bendamustin hydrochloride, bendamustine, cytostasan hydrochloride, Treanda
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Adverse Events in Terms of Dose-limiting Toxicity (DLT) and MTD of Bendamustine Hydrochloride (Phase I)
Description
Dose limiting toxicity will be defined during cycle 1 only of the phase I trial. Hematologic and Infectious Dose Limiting Toxicities include: Grade 3 febrile neutropenia persisting> 7 days, Grade 4 infection or febrile neutropenia. Treatment delay>14 days due to grade 3-4 neutropenia or thrombocytopenia. Non-Hematological Dose Limiting Toxicities include: any Grade 3 or 4 non-hematologic toxicity related to study treatment with the exception of nausea or vomiting, alopecia, or electrolyte/glucose abnormalities that are correctable within 72 hours.
Time Frame
up to 5 years
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR) of Bendamustine Hydrochloride and Gemcitabine Hydrochloride in Patients With Relapsed or Refractory Hodgkin Lymphoma (Phase II)
Description
Tested using Simon's two-stage Minimax design. Descriptive statistics (i.e. means, standard deviations, 95% confidence intervals for continuous variables, and frequencies for discrete data) and graphical analyses will be used for all correlative laboratory parameters. The associations between correlative laboratory parameters and clinical response will be evaluated using two sample t test or Fisher's exact test, whichever is appropriate.
Time Frame
up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically documented Classical Hodgkin's 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 Patients with Hodgkin's lymphoma may have one of the following World Health Organization subtypes: Nodular sclerosis Hodgkin's lymphoma Lymphocyte-rich Hodgkin's lymphoma Mixed cellularity Hodgkin's lymphoma Lymphocyte depletion Hodgkin's lymphoma Nodular lymphocyte predominant Hodgkin's lymphoma Patients must have relapsed or progressed after at least one prior therapy Patients with relapsed or refractory disease following stem cell transplantation are permitted No prior treatment with bendamustine; prior therapy with gemcitabine is permitted 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), PET/CT (positron emission tomography/CT), or magnetic resonance imaging (MRI) 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's lymphoma should be noted) Non-pregnant and non-nursing; due to the teratogenic potential of these agents, pregnant or nursing patients may not be enrolled; 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 (CD)4+ 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; no history of acquired immune deficiency syndrome (AIDS) defining conditions Granulocytes >= 1000/μl Platelet count >= 75,000/μl Creatinine =< 20 mg/dL Bilirubin =< 2.0 mg/dL Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.0 x upper limits of normal
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Beth Christian, MD
Organizational Affiliation
Ohio State University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Ohio State University Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
31821549
Citation
Cohen JB, Wei L, Maddocks KJ, Christian B, Heffner LT, Langston AA, Lechowicz MJ, Porcu P, Flowers CR, Devine SM, Blum KA. Gemcitabine and bendamustine is a safe and effective salvage regimen for patients with recurrent/refractory Hodgkin lymphoma: Results of a phase 1/2 study. Cancer. 2020 Mar 15;126(6):1235-1242. doi: 10.1002/cncr.32640. Epub 2019 Dec 10.
Results Reference
background
Links:
URL
http://cancer.osu.edu
Description
Jamesline

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Gemcitabine and Bendamustine in Patients With Relapsed or Refractory Hodgkin's Lymphoma

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