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

Gemcitabine and High-dose Chemotherapy Followed by Peripheral Blood Stem Cell Rescue for Relapsed or Resistant Hodgkin's Disease

This is a phase 2 study of gemcitabine + high-dose chemotherapy followed by peripheral blood stem cell (PBSC) rescue for Hodgkin's Disease

Study Overview

• Status: Completed
• Conditions: Lymphoma; Hodgkin's Lymphoma; Hodgkin Disease
• Intervention / Treatment: Drug: Gemcitabine; Drug: Cyclophosphamide; Drug: Etoposide; Drug: Vinorelbine; Drug: Carmustine; Procedure: Autologous HCT

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 Type: Interventional
• Enrollment (Actual): 146
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gemcitabine + Autologous HCT; Gemcitabine and high-dose chemotherapy followed by peripheral blood stem cell (PBSC) rescue. Chemotherapy includes Gemcitabine + Vinorelbine + Carmustine + Etoposide + Cyclophosphamide.	Drug: Gemcitabine; Other Names: Gemzar; Drug: Cyclophosphamide; Other Names: Cytoxan; Neosar; Drug: Etoposide; Other Names: Vepesid; Drug: Vinorelbine; Other Names: Navelbine; Drug: Carmustine; Other Names: BCNU; Procedure: Autologous HCT; Other Names: Peripheral blood stem cell (PBSC) rescue

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary Toxicity (BCNU Pneumonitis)	Pulmonary toxicity as assessed by the number of participants that experience BCNU pneumonitis, ie, pneumonitis due to carmustine (BCNU).	2 years
Overall Survival (OS)	Reports the percentage of participants surviving 6 months after PBSC infusion (transplant).	2 years
Relapse Post-transplant	Reports the percentage of participants that experienced relapse post-transplant.	2 years
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	2 years

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Sally Arai, MD, Stanford University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2001
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: October 12, 2006
• First Submitted That Met QC Criteria: October 13, 2006
• First Posted (Estimate): October 16, 2006

Study Record Updates

• Last Update Posted (Actual): June 14, 2017
• Last Update Submitted That Met QC Criteria: May 15, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Gemcitabine; Cyclophosphamide; Etoposide; Vinorelbine; Carmustine
• Other Study ID Numbers: IRB-13511; 1K23AI052413-01A1 (U.S. NIH Grant/Contract); BMT135 (Other Identifier: OnCore)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No