Gemcitabine and Hodgkin's Disease Chemotherapy Followed by Peripheral Blood Stem Cell Rescue for Hodgkin's Disease

Phase 2

Completed

• Conditions: Hodgkin Disease; Hodgkin's Lymphoma; Lymphoma
• Interventions: Drug: Gemcitabine; Drug: Vinorelbine; Drug: Carmustine; Drug: Etoposide; Drug: Cyclophosphamide; Procedure: Autologous HCT

• Registration Number: NCT00388349
• Lead Sponsor: Stanford University

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

Study Timeline

• Study Start: 2001-09
• Study First Submitted: 2006-10-12
• Study First Submitted QC: 2006-10-13
• Study First Posted: 2006-10-16
• Primary Completion: 2008-03
• Study Completion: 2010-09
• Results First Submitted: 2017-01-09
• Status Verified: 2017-05
• Results First Submitted QC: 2017-05-15
• Last Update Submitted: 2017-05-15
• Results First Posted: 2017-06-14
• Last Update Posted: 2017-06-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 146

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Gemcitabine + Autologous HCT	Gemcitabine	Gemcitabine and high-dose chemotherapy followed by peripheral blood stem cell (PBSC) rescue. Chemotherapy includes Gemcitabine + Vinorelbine + Carmustine + Etoposide + Cyclophosphamide.
Gemcitabine + Autologous HCT	Vinorelbine	Gemcitabine and high-dose chemotherapy followed by peripheral blood stem cell (PBSC) rescue. Chemotherapy includes Gemcitabine + Vinorelbine + Carmustine + Etoposide + Cyclophosphamide.
Gemcitabine + Autologous HCT	Etoposide	Gemcitabine and high-dose chemotherapy followed by peripheral blood stem cell (PBSC) rescue. Chemotherapy includes Gemcitabine + Vinorelbine + Carmustine + Etoposide + Cyclophosphamide.
Gemcitabine + Autologous HCT	Autologous HCT	Gemcitabine and high-dose chemotherapy followed by peripheral blood stem cell (PBSC) rescue. Chemotherapy includes Gemcitabine + Vinorelbine + Carmustine + Etoposide + Cyclophosphamide.
Gemcitabine + Autologous HCT	Carmustine	Gemcitabine and high-dose chemotherapy followed by peripheral blood stem cell (PBSC) rescue. Chemotherapy includes Gemcitabine + Vinorelbine + Carmustine + Etoposide + Cyclophosphamide.
Gemcitabine + Autologous HCT	Cyclophosphamide	Gemcitabine and high-dose chemotherapy followed by peripheral blood stem cell (PBSC) rescue. Chemotherapy includes Gemcitabine + Vinorelbine + Carmustine + Etoposide + Cyclophosphamide.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Stanford University School of Medicine; 🇺🇸 Stanford, California, United States