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

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00388349
• Collaborator: National Institutes of Health (NIH) (NIH), National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Enrollment: 146
• Location: 1
• Arm: 1
• Duration (Months): 108
• Patients Per Site Per Month: 1.4

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Hodgkin Disease; Hodgkin's Lymphoma; Lymphoma	Drug: Gemcitabine; Drug: Vinorelbine; Drug: Carmustine; Drug: Etoposide; Drug: Cyclophosphamide; Procedure: Autologous HCT	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 146 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Gemcitabine and High-dose Chemotherapy Followed by Peripheral Blood Stem Cell Rescue for Relapsed or Resistant Hodgkin's Disease
• Study Start Date: Sep 1, 2001
• Actual Primary Completion Date: Mar 1, 2008
• Actual Study Completion Date: Sep 1, 2010

Arms and Interventions

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: Vinorelbine; Other Names: Navelbine ; Drug: Carmustine; Other Names: BCNU ; Drug: Etoposide; Other Names: Vepesid ; Drug: Cyclophosphamide; Other Names: Cytoxan Neosar ; Procedure: Autologous HCT; Other Names: Peripheral blood stem cell (PBSC) rescue

Outcome Measures

Primary Outcome Measures

1. 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

1. 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).

2. Overall Survival (OS) [2 years]

   Reports the percentage of participants surviving 6 months after PBSC infusion (transplant).

3. Relapse Post-transplant [2 years]

   Reports the percentage of participants that experienced relapse post-transplant.

4. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University
• National Institutes of Health (NIH)
• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Principal Investigator: Sally Arai, MD, Stanford University

Study Documents (Full-Text)

None provided.

More Information

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.

• Responsible Party: Sally Arai, Assistant Professor of Medicine, Stanford University
• ClinicalTrials.gov Identifier: NCT00388349
• Other Study ID Numbers: IRB-13511; 1K23AI052413-01A1; BMT135
• First Posted: Oct 16, 2006
• Last Update Posted: Jun 14, 2017
• Last Verified: May 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lymphoma; Hodgkin Disease; Gemcitabine; Cyclophosphamide; Carmustine; Etoposide; Vinorelbine

Study Results

Participant Flow

Arm/Group Title	1250 mg/m2 Gemcitabine + High-dose Chemotherapy + PBSC Rescue	1500 mg/m2 Gemcitabine + High-dose Chemotherapy + PBSC Rescue
Arm/Group Description	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)].	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)].
Period Title: Phase I Dose Escalation
STARTED	3	4
COMPLETED	3	1
NOT COMPLETED	0	3
Period Title: Phase I Dose Escalation
STARTED	139	0
COMPLETED	139	0
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Gemcitabine + High-dose Chemotherapy + PBSC Rescue
Arm/Group Description	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)].
Overall Participants	146
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	145 99.3%
>=65 years	1 0.7%
Sex: Female, Male (Count of Participants)
Female	63 43.2%
Male	83 56.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	23 15.8%
Not Hispanic or Latino	119 81.5%
Unknown or Not Reported	4 2.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	7 4.8%
Native Hawaiian or Other Pacific Islander	3 2.1%
Black or African American	3 2.1%
White	105 71.9%
More than one race	1 0.7%
Unknown or Not Reported	27 18.5%

Outcome Measures

1. Primary Outcome

Title	Dose-limiting Toxicity of Gemcitabine Due to Non-hematologic Toxicity
Description	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

Outcome Measure Data

Analysis Population Description

7 patients received 1 of 2 dose levels during the Phase 1 dose-escalation component of the study

Arm/Group Title	1250 mg/m2 Gemcitabine + HD Chemo + PBSC Rescue	1500 mg/m2 Gemcitabine + HD Chemo + PBSC Rescue
Arm/Group Description	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)].	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)].
Measure Participants	3	4
Number [participants]	0 0%	3 NaN

2. Secondary Outcome

Title	Pulmonary Toxicity (BCNU Pneumonitis)
Description	Pulmonary toxicity as assessed by the number of participants that experience BCNU pneumonitis, ie, pneumonitis due to carmustine (BCNU).
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Patients who completed the study regardless of gemcitabine dose, and had all data points collected.

Arm/Group Title	Gemcitabine + High-dose Chemotherapy + PBSC Rescue
Arm/Group Description	Gemcitabine (1250 or 1500 mg/m2) 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)].
Measure Participants	146
Number [participants]	26 17.8%

3. Secondary Outcome

Title	Overall Survival (OS)
Description	Reports the percentage of participants surviving 6 months after PBSC infusion (transplant).
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	Gemcitabine + High-dose Chemotherapy + PBSC Rescue
Arm/Group Description	Gemcitabine (1250 or 1500 mg/m2) 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)].
Measure Participants	146
Number [percentage of participants]	87 59.6%

4. Secondary Outcome

Title	Relapse Post-transplant
Description	Reports the percentage of participants that experienced relapse post-transplant.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	Gemcitabine + High-dose Chemotherapy + PBSC Rescue
Arm/Group Description	Gemcitabine (1250 or 1500 mg/m2) 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)].
Measure Participants	146
Number [percentage of participants]	29 19.9%

5. Secondary Outcome

Title	Survival Measures
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	1250 mg/m2 Gemcitabine + High-dose Chemotherapy + PBSC Rescue
Arm/Group Description	Gemcitabine 1250 mg/m2 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)].
Measure Participants	92
Freedom from Progression (FFP)	71
Event-Free Survival (EFS)	67
Overall Survival (OS)	83

Adverse Events

Time Frame	2 years
Adverse Event Reporting Description	All events reported.
Arm/Group Title	Gemcitabine + High-dose Chemotherapy + PBSC Rescue
Arm/Group Description	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)].
All Cause Mortality
	Gemcitabine + High-dose Chemotherapy + PBSC Rescue
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Gemcitabine + High-dose Chemotherapy + PBSC Rescue
	Affected / at Risk (%)	# Events
Total	31/146 (21.2%)
Blood and lymphatic system disorders
Discharge	1/146 (0.7%)	1
Cardiac disorders
Cardiac ischemia	1/146 (0.7%)	1
Ventricular arythmia	1/146 (0.7%)	1
Supraventricular tachycardia	1/146 (0.7%)	1
Veno-occlusive disease	2/146 (1.4%)	2
Respiratory distress	1/146 (0.7%)	1
Tachypenic	3/146 (2.1%)	3
Gastrointestinal disorders
Constipation	3/146 (2.1%)	3
Bowel obstruction	2/146 (1.4%)	2
General disorders
Fever	2/146 (1.4%)	2
Failed to engraft	1/146 (0.7%)	1
Allergic reaction	1/146 (0.7%)	1
Intubated	1/146 (0.7%)	1
Multisystem organ failure	2/146 (1.4%)	2
Fatigue	1/146 (0.7%)	1
Death	2/146 (1.4%)	21
Infections and infestations
osteomyelitis	1/146 (0.7%)	1
Relapse	1/146 (0.7%)	1
Neutropenia	1/146 (0.7%)	1
Septic shock	1/146 (0.7%)	1
Metabolism and nutrition disorders
Metabolic abnormalities	1/146 (0.7%)	1
Renal and urinary disorders
Progressive liver failure	1/146 (0.7%)	1
Other (Not Including Serious) Adverse Events
	Gemcitabine + High-dose Chemotherapy + PBSC Rescue
	Affected / at Risk (%)	# Events
Total	17/146 (11.6%)
Blood and lymphatic system disorders
Friable fascial plane	1/146 (0.7%)	1
Elevated troponin	1/146 (0.7%)	1
Nodular infiltrates	1/146 (0.7%)	1
Cardiac disorders
Arrhythmias	1/146 (0.7%)	1
Chest pain	1/146 (0.7%)	1
Ventricular tachycardia	1/146 (0.7%)	1
Gastrointestinal disorders
Abdominal pain	1/146 (0.7%)	1
Ileus	1/146 (0.7%)	1
Bowel obstruction	1/146 (0.7%)	1
Infections and infestations
Bacteremia	1/146 (0.7%)	1
Candida albicans	1/146 (0.7%)	1
Neutropenic fever	1/146 (0.7%)	1
Renal and urinary disorders
Urinary tract infection	1/146 (0.7%)	1
Respiratory, thoracic and mediastinal disorders
diffusing capacity of the lung for carbon monoxide (DLCO)	1/146 (0.7%)	1
Dyspnea on exertion	1/146 (0.7%)	1
Parpneumonic effusion	1/146 (0.7%)	1
Pneumonia	1/146 (0.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.