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
Conditions
Keywords
Hodgkin's Lymphoma, relapsed, refractory
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.
Interventions
DRUGgemcitabine hydrochloride
Given IV
DRUGbendamustine hydrochloride
Given IV
Sponsors
Beth Christian
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events in Terms of Dose-limiting Toxicity (DLT) and MTD of Bendamustine Hydrochloride (Phase I) | up to 5 years | 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
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) of Bendamustine Hydrochloride and Gemcitabine Hydrochloride in Patients With Relapsed or Refractory Hodgkin Lymphoma (Phase II) | up to 5 years | 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. |
Countries
United States
Participant flow
Recruitment details
The current study was conducted at the Ohio State University in Columbus, Ohio, and Emory University in Atlanta, Georgia.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1 (Dose Levels 1) Dose Level 1: Patients receive Gemcitabine 1000 mg/m2 IV over 30 minutes on day 1 and Bendamustine 60 mg/m2 IV over 30 minutes on days 1 and 2. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
gemcitabine hydrochloride: Given IV bendamustine hydrochloride: Given IV | 3 |
| Phase 1 (Dose Levels 2) Dose Level 2: Patients receive Gemcitabine 1000 mg/m2 IV over 30 minutes on day 1 and Bendamustine 90 mg/m2 IV over 30 minutes on days 1 and 2. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. | 3 |
| Phase 1 (Dose Levels 3) Dose Level 3: Patients receive Gemcitabine 1000 mg/m2 IV over 30 minutes on day 1 and Bendamustine 120 mg/m2 IV over 30 minutes on days 1 and 2. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. | 3 |
| Phase 1 (Dose Levels 4) Dose Level 4: Patients receive Gemcitabine 1000 mg/m2 IV over 30 minutes on day 1 and Bendamustine 90 mg/m2 IV over 30 minutes on days 1 and 2. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. | 4 |
| Phase 2 (Dose Levels 5) Patients receive Gemcitabine 1000mg/m2 on day 1 and Bendamustine 120mg/m2 on days 1 and 2 of each 21 day cycle. Gemcitabine shall be administered prior to Bendamustine on day 1 of each cycle. | 6 |
| Phase 2 Patients receive Gemcitabine 1000mg/m2 on day 1 and Bendamustine 120mg/m2 on days 1 and 2 of each 21 day cycle. Gemcitabine shall be administered prior to Bendamustine on day 1 of each cycle. | 7 |
| Total | 26 |
Baseline characteristics
| Characteristic | Phase 1 (Dose Levels 1) | Total | Phase 2 | Phase 2 (Dose Levels 5) | Phase 1 (Dose Levels 4) | Phase 1 (Dose Levels 3) | Phase 1 (Dose Levels 2) |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 38 years STANDARD_DEVIATION 17.34 | 38.19 years STANDARD_DEVIATION 12.82 | 37.14 years STANDARD_DEVIATION 12.03 | 33.33 years STANDARD_DEVIATION 16.05 | 50 years STANDARD_DEVIATION 7.78 | 35 years STANDARD_DEVIATION 11.63 | 38 years STANDARD_DEVIATION 9.16 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 25 Participants | 6 Participants | 6 Participants | 4 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 21 Participants | 6 Participants | 5 Participants | 4 Participants | 1 Participants | 2 Participants |
| Region of Enrollment United States | 3 patients | 26 patients | 7 patients | 6 patients | 4 patients | 3 patients | 3 patients |
| Sex: Female, Male Female | 1 Participants | 10 Participants | 2 Participants | 3 Participants | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 2 Participants | 16 Participants | 5 Participants | 3 Participants | 3 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 4 | 0 / 6 | 0 / 7 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 4 / 4 | 6 / 6 | 7 / 7 |
| serious Total, serious adverse events | 0 / 3 | 3 / 3 | 0 / 3 | 4 / 4 | 1 / 6 | 1 / 7 |
Outcome results
Primary
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.
Time frame: up to 5 years
Population: Only patients in Phase I analyzed
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1 (Dose Levels 1) | Adverse Events in Terms of Dose-limiting Toxicity (DLT) and MTD of Bendamustine Hydrochloride (Phase I) | 0 number of patients |
| Phase 1 (Dose Levels 2) | Adverse Events in Terms of Dose-limiting Toxicity (DLT) and MTD of Bendamustine Hydrochloride (Phase I) | 0 number of patients |
| Phase 1 (Dose Levels 3) | Adverse Events in Terms of Dose-limiting Toxicity (DLT) and MTD of Bendamustine Hydrochloride (Phase I) | 0 number of patients |
| Phase 1 (Dose Levels 4) | Adverse Events in Terms of Dose-limiting Toxicity (DLT) and MTD of Bendamustine Hydrochloride (Phase I) | 0 number of patients |
Secondary
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.
Time frame: up to 5 years
Population: Only patients in Phase II analyzed
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 2 (Dose Levels 5) | Overall Response Rate (ORR) of Bendamustine Hydrochloride and Gemcitabine Hydrochloride in Patients With Relapsed or Refractory Hodgkin Lymphoma (Phase II) | 67 percentage of patients |
| Phase 2 | Overall Response Rate (ORR) of Bendamustine Hydrochloride and Gemcitabine Hydrochloride in Patients With Relapsed or Refractory Hodgkin Lymphoma (Phase II) | 71 percentage of patients |