Hodgkin Disease, Hodgkin's Lymphoma, Lymphoma
Conditions
Brief summary
This is a phase 2 study of gemcitabine + high-dose chemotherapy followed by peripheral blood stem cell (PBSC) rescue for Hodgkin's Disease
Detailed description
To assess the non-hematologic toxicity and determine the phase 2 dose of gemcitabine in combination with vinorelbine followed by carmustine, etoposide and cyclophosphamide and autologous hematopoietic stem cell transplantation \[aka peripheral blood stem cell (PBSC)\].
Interventions
DRUGGemcitabine
DRUGVinorelbine
DRUGCarmustine
DRUGEtoposide
DRUGCyclophosphamide
PROCEDUREAutologous HCT
Sponsors
National Institutes of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Histologically-proven recurrent or refractory Hodgkin's Disease (Hodgkin's lymphoma) on the basis of excisional biopsy whenever possible. * Age \< 70 years * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 3. * Phase 1 study component only: 1 or more of the following adverse risk factors * Stage IV extranodal disease at relapse B symptoms * Failure to achieve minimal disease with most recent chemotherapy (single lymph nodes \< 2 cm or \>75% reduction in a bulky tumor mass and bone marrow involvement \< 10%) * Progression during induction or salvage therapy * Phase 2 study component only: No risk factor criteria * Computerized tomography (CT) scan of the chest, abdomen and pelvis, with assessment of response to last chemotherapy, within 4 weeks of registration. Gallium scan or positron emission tomography (PET) scan confirmation of disease within 4 weeks of registration is highly recommended * Bone marrow biopsy and cytogenetic analysis within 8 weeks of registration * Women of child-bearing potential and sexually active males expected to use an accepted and effective method of birth control * Pretreatment serum bilirubin \< 2 x the institutional upper limit of normal (ULN) (within 28 days prior to registration) * Serum creatinine \< 2 x the institutional ULN (within 28 days prior to registration) * Measured or estimated creatinine clearance \> 60 cc/min by the following formula (within 28 days prior to registration): * Estimated Creatinine Clearance = (140 age) x WT(kg) x 0.85 (if female) x creatinine (mg/dL) * Electrocardiogram (ECG) demonstrating no significant abnormalities suggestive of active cardiac disease (within 42 days prior to registration) * Patients over age 50, who have received chest irradiation or a total of 300 mg/m2 of doxorubicin or with any history of cardiac disease must have a radionuclide ejection fraction (within 42 days prior to registration). If the ejection fraction is 40 to 50%, the patient will have a cardiology consult * Corrected diffusion capacity \> 55% * Written informed consent in accordance with institutional and federal guidelines
Exclusion criteria
* Positive HIV antibody test (must be conducted within 42 days of registration) * No chemotherapy other than corticosteroids should be administered within 2 weeks of the initiation of protocol therapy * Pregnant * Breast-feeding * Requiring therapy for: * Coronary artery disease * Cardiomyopathy * Dysrhythmia, or * Congestive heart failure * Over age 50 and has received chest irradiation or a total of 300 mg/m\^2 of doxorubicin * History of cardiac disease and the ejection fraction is \< 40% (radionuclide ejection fraction must be within 42 days of registration) * Known allergy to etoposide * History of Grade 3 hemorrhagic cystitis with cyclophosphamide * History of grade 2 or greater sensory or motor peripheral neuropathy due to prior vinca alkaloid use * No prior malignancy (EXCEPTION: adequately treated basal cell or squamous cell skin cancer; in situ cervical cancer; or other cancer for which the patients has been disease-free for 5 years). Patients with a prior diagnosis of non-Hodgkin's lymphoma are not eligible.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting Toxicity of Gemcitabine Due to Non-hematologic Toxicity | 6 months | Reported as the number of Phase 1 participants by gemcitabine dose that experienced non-hematologic toxicity, ie, drug-related adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pulmonary Toxicity (BCNU Pneumonitis) | 2 years | Pulmonary toxicity as assessed by the number of participants that experience BCNU pneumonitis, ie, pneumonitis due to carmustine (BCNU). |
| Overall Survival (OS) | 2 years | Reports the percentage of participants surviving 6 months after PBSC infusion (transplant). |
| Relapse Post-transplant | 2 years | Reports the percentage of participants that experienced relapse post-transplant. |
| Survival Measures | 2 years | Reports the survival measures: * Freedom from progression (FFP) * Event-free survival (EFS) * Overall survival (OS) EFS and OS were estimated by Kaplan-Meier method Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gemcitabine + High-dose Chemotherapy + PBSC Rescue Gemcitabine as administered in combination with vinorelbine, and then followed by high-dose carmustine + etoposide + cyclophosphamide, then autologous peripheral blood stem cell (PBSC) rescue \[aka, hematopoietic stem cell transplantation (AHCT)\]. | 146 |
| Total | 146 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Phase I Dose Escalation | Dose reduction due to DLT | 0 | 3 |
Baseline characteristics
| Characteristic | Gemcitabine + High-dose Chemotherapy + PBSC Rescue |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 145 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 119 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 27 Participants |
| Race (NIH/OMB) White | 105 Participants |
| Sex: Female, Male Female | 63 Participants |
| Sex: Female, Male Male | 83 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 17 / 146 |
| serious Total, serious adverse events | 31 / 146 |
Outcome results
Primary
Dose-limiting Toxicity of Gemcitabine Due to Non-hematologic Toxicity
Reported as the number of Phase 1 participants by gemcitabine dose that experienced non-hematologic toxicity, ie, drug-related adverse events.
Time frame: 6 months
Population: 7 patients received 1 of 2 dose levels during the Phase 1 dose-escalation component of the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1250 mg/m2 Gemcitabine + HD Chemo + PBSC Rescue | Dose-limiting Toxicity of Gemcitabine Due to Non-hematologic Toxicity | 0 participants |
| 1500 mg/m2 Gemcitabine + HD Chemo + PBSC Rescue | Dose-limiting Toxicity of Gemcitabine Due to Non-hematologic Toxicity | 3 participants |
Secondary
Overall Survival (OS)
Reports the percentage of participants surviving 6 months after PBSC infusion (transplant).
Time frame: 2 years
Population: All participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1250 mg/m2 Gemcitabine + HD Chemo + PBSC Rescue | Overall Survival (OS) | 87 percentage of participants |
Secondary
Pulmonary Toxicity (BCNU Pneumonitis)
Pulmonary toxicity as assessed by the number of participants that experience BCNU pneumonitis, ie, pneumonitis due to carmustine (BCNU).
Time frame: 2 years
Population: Patients who completed the study regardless of gemcitabine dose, and had all data points collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1250 mg/m2 Gemcitabine + HD Chemo + PBSC Rescue | Pulmonary Toxicity (BCNU Pneumonitis) | 26 participants |
Secondary
Relapse Post-transplant
Reports the percentage of participants that experienced relapse post-transplant.
Time frame: 2 years
Population: All participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1250 mg/m2 Gemcitabine + HD Chemo + PBSC Rescue | Relapse Post-transplant | 29 percentage of participants |
Secondary
Survival Measures
Reports the survival measures: * Freedom from progression (FFP) * Event-free survival (EFS) * Overall survival (OS) EFS and OS were estimated by Kaplan-Meier method Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: 2 years
Population: Lists the results as included in the publication, which included 92 participants who received the MTD treatment; completed the study; and had all data points collected
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1250 mg/m2 Gemcitabine + HD Chemo + PBSC Rescue | Survival Measures | Freedom from Progression (FFP) | 71 percentage of patients |
| 1250 mg/m2 Gemcitabine + HD Chemo + PBSC Rescue | Survival Measures | Event-Free Survival (EFS) | 67 percentage of patients |
| 1250 mg/m2 Gemcitabine + HD Chemo + PBSC Rescue | Survival Measures | Overall Survival (OS) | 83 percentage of patients |