Clinical trial NCT00388349: Gemcitabine and Hodgkin's Disease Chemotherapy Followed by Peripheral Blood Stem Cell Rescue for Hodgkin's Disease
Official title: Gemcitabine and High-dose Chemotherapy Followed by Peripheral Blood Stem Cell Rescue for Relapsed or Resistant Hodgkin's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hodgkin Disease
Hodgkin's Lymphoma
Lymphoma
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2006-10-16
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 \[aka peripheral blood stem cell (PBSC)\].

Eligibility criteria: 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.

Primary outcomes:
measure: Dose-limiting Toxicity of Gemcitabine Due to Non-hematologic Toxicity
timeFrame: 6 months
Secondary outcomes:
measure: Pulmonary Toxicity (BCNU Pneumonitis)
timeFrame: 2 years
measure: Overall Survival (OS)
timeFrame: 2 years
measure: Relapse Post-transplant
timeFrame: 2 years
measure: Survival Measures
timeFrame: 2 years
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Sally Arai, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Arai S, Letsinger R, Wong RM, Johnston LJ, Laport GG, Lowsky R, Miklos DB, Shizuru JA, Weng WK, Lavori PW, Blume KG, Negrin RS, Horning SJ. Phase I/II trial of GN-BVC, a gemcitabine and vinorelbine-containing conditioning regimen for autologous hematopoietic cell transplantation in recurrent and refractory hodgkin lymphoma. Biol Blood Marrow Transplant. 2010 Aug;16(8):1145-54. doi: 10.1016/j.bbmt.2010.02.022. Epub 2010 Mar 1.