Rituximab, Cyclophosphamide, and Pegfilgrastim in Treating Patients With Leukemia or Non-Hodgkin's Lymphoma
Official Title
Phase II Study of High Dose Cyclophosphamide and Rituximab in Low Grade and Mantle Cell Lymphoma
Acronym
Not provided
Organization
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsOTHER
Status Module
Record Verification Date
Oct 2018
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jan 2005
Primary Completion Date
Dec 2009Actual
Completion Date
Jul 2011Actual
First Submitted Date
Jan 16, 2006
First Submission Date that Met QC Criteria
Jan 16, 2006
First Posted Date
Jan 18, 2006Estimated
Results Waived
Not provided
Results First Submitted Date
Oct 4, 2018
Results First Submitted that Met QC Criteria
Oct 31, 2018
Results First Posted Date
Nov 5, 2018Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Oct 31, 2018
Last Update Posted Date
Nov 5, 2018Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsOTHER
Collaborators
Name
Class
National Cancer Institute (NCI)
NIH
Oversight Module
No data available
No data is available for this block.
Description Module
Brief Summary
RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Colony-stimulating factors, such as pegfilgrastim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Giving rituximab and cyclophosphamide together with pegfilgrastim may be effective in treating leukemia or non-Hodgkin's lymphoma.
PURPOSE: This phase II trial is studying how well giving rituximab and cyclophosphamide together with pegfilgrastim works in treating patients with B-cell leukemia, low-grade non-Hodgkin's lymphoma, or mantle cell lymphoma.
Detailed Description
OBJECTIVES:
Determine the safety of high-dose cyclophosphamide, rituximab, and pegfilgrastim in patients with B-cell leukemia or low-grade or mantle cell lymphoma.
Determine the molecular response rate in patients treated with this regimen.
OUTLINE: This is an open-label study.
Patients receive rituximab IV over 30-60 minutes on days 1, 4, 8,11, 45, and 52, cyclophosphamide IV over 1 hour on days 15-18, and pegfilgrastim subcutaneously on day 19 or 20 in the absence of unacceptable toxicity.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 32 patients will be accrued for this study.
Conditions Module
Conditions
Leukemia
Lymphoma
Keywords
stage 0 chronic lymphocytic leukemia
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
small lymphocytic lymphoma
stage I small lymphocytic lymphoma
stage III small lymphocytic lymphoma
stage IV small lymphocytic lymphoma
B-cell chronic lymphocytic leukemia
splenic marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
stage I grade 1 follicular lymphoma
stage I grade 2 follicular lymphoma
stage III grade 1 follicular lymphoma
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
94Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
R-HiCy
Experimental
Rituximab (R) and high-dose cyclophosphamide (HiCy) with pegfilgrastim support.
Biological: Pegfilgrastim
Biological: Rituximab
Drug: Cyclophosphamide
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Pegfilgrastim
Biological
6 mg SQ 24-48 hours after last dose of cyclophosphamide.
R-HiCy
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Engraftment
Median days to neutrophil and platelet recovery. Neutrophil recovery is defined as absolute neutrophil count >= 500 cells per microliter; platelet recovery is defined as untransfused platelet count >= 20 * 10^9 cells per liter.
Up to 43 days
Non-relapse Mortality
Number of participants who died for reasons related to protocol treatment.
5 years
Event-free Survival
Percentage of participants alive without disease relapse.
5 years
Secondary Outcomes
Not provided
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
DISEASE CHARACTERISTICS:
One of the following B-cell leukemias or lymphomas, as defined by World Health Organization criteria:
Marginal zone lymphoma (splenic, extranodal, or nodal)
Follicular lymphoma (grade 1 or 2)
Mantle cell lymphoma
No more than minimal (approximately 10%) morphologically identifiable cancer cells on bone marrow biopsy
When cancer cells are morphologically difficult to distinguish from normal cells, flow cytometry must show no more than 10% identifiable cancer cells
Must have received ≤ 12 months of prior cytotoxic therapy, achieving at least a partial response NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.
PATIENT CHARACTERISTICS:
ECOG performance status 0-1
WBC ≥ 3,000/mm^3
Hemoglobin ≥ 10.0 g/dL
Platelet count ≥ 75,000/mm^3
Serum creatinine ≤ 2.0 mg/dL
Total bilirubin ≤ 2 mg/dL unless secondary to tumor
AST or ALT < 2 times upper limit of normal
Normal (≥ 45%) left ventricular cardiac ejection fraction (determined by echocardiogram or MUGA scan)
DLCO > 50% predicted
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No known sensitivity to E. coli-derived products (e.g. filgrastim [G-CSF], insulin, asparaginase, growth hormone, or recombinant interferon alfa-2b) or any treatment study drugs
No active infections requiring oral or intravenous antibiotics
No other second malignancy other than basal cell or squamous cell carcinoma of the skin or in situ carcinoma of the cervix unless the malignancy was localized and treated or resected with > 90% probability of cure
PRIOR CONCURRENT THERAPY:
See Disease Characteristics
Prior anti-CD20 therapy allowed provided patient achieved a partial or complete response
No concurrent steroids during rituximab administration
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
70 Years
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Lode J. Swinnen, MD
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Chair
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Gladstone DE, Bolanos-Meade J, Huff CA, Zahurak M, Flinn I, Borrello I, Luznik L, Fuchs E, Kasamon Y, Matsui W, Powell J, Levitsky H, Brodsky RA, Ambinder R, Jones RJ, Swinnen LJ. High-dose cyclophosphamide and rituximab without stem cell transplant: a feasibility study for low grade B-cell, transformed and mantle cell lymphomas. Leuk Lymphoma. 2011 Nov;52(11):2076-81. doi: 10.3109/10428194.2011.594191. Epub 2011 Jul 14.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
Plan to Share IPD
No
Description
Not provided
Types
Not provided
Time Frame
Not provided
Access Criteria
Not provided
URL
Not provided
16 participants were screen failures. IRB allowed 3 of those participants to be analyzed along with the 78 who were treated as part of the study. Because the 3 additional participants received the exact same protocol intervention, the total population for analysis purposes is 81.
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
R-HiCy
Rituximab (R) and high-dose cyclophosphamide (HiCy) with pegfilgrastim support.
Pegfilgrastim: 6 mg SQ 24-48 hours after last dose of cyclophosphamide.
Rituximab: 375 mg/m^2/day on Days 1, 4, 8, 11, 45, and 52.
Cyclophosphamide: 50 mg/kg/day on Days 15, 16, 17, and 18.
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
FG00081 subjects
COMPLETED
FG00070 subjects
NOT COMPLETED
FG00011 subjects
Type
Comment
Reasons
Death
FG00011 subjects
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
R-HiCy
Rituximab (R) and high-dose cyclophosphamide (HiCy) with pegfilgrastim support.
Pegfilgrastim: 6 mg SQ 24-48 hours after last dose of cyclophosphamide.
Rituximab: 375 mg/m^2/day on Days 1, 4, 8, 11, 45, and 52.
Cyclophosphamide: 50 mg/kg/day on Days 15, 16, 17, and 18.
Denominators
Units
Counts
Participants
BG000
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Categorical
Count of Participants
Outcome Measures Module
Outcome Measures
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Engraftment
Median days to neutrophil and platelet recovery. Neutrophil recovery is defined as absolute neutrophil count >= 500 cells per microliter; platelet recovery is defined as untransfused platelet count >= 20 * 10^9 cells per liter.
Posted
Median
Full Range
days
Up to 43 days
ID
Title
Description
OG000
R-HiCy
Rituximab (R) and high-dose cyclophosphamide (HiCy) with pegfilgrastim support.
Pegfilgrastim: 6 mg SQ 24-48 hours after last dose of cyclophosphamide.
Rituximab: 375 mg/m^2/day on Days 1, 4, 8, 11, 45, and 52.
Cyclophosphamide: 50 mg/kg/day on Days 15, 16, 17, and 18.
Units
Counts
Participants
Adverse Events Module
Frequency Threshold
5
Time Frame
Up to 1 year
Description
Adverse events were assessed at least weekly through Day 60, then at Day 180 and one year.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
R-HiCy
Rituximab (R) and high-dose cyclophosphamide (HiCy) with pegfilgrastim support.
Pegfilgrastim: 6 mg SQ 24-48 hours after last dose of cyclophosphamide.
Rituximab: 375 mg/m^2/day on Days 1, 4, 8, 11, 45, and 52.
Cyclophosphamide: 50 mg/kg/day on Days 15, 16, 17, and 18.
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Atrial fibrillation with rapid ventricular response
Cardiac disorders
CTCAE (3.0)
Systematic Assessment
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
ALT high
Investigations
CTCAE (3.0)
Systematic Assessment
More Info Module
Limitations and Caveats
Not provided
Certain Agreements
Are all PI(s) employees of the sponsor?
Yes
Restriction Type
Point of Contact
Title
Organization
Phone
Extension
Email
Lode Swinnen, MD
Johns Hopkins University
4106146398
lswinne1@jhmi.edu
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
ID
Term
D007938
Leukemia
D008223
Lymphoma
D015451
Leukemia, Lymphocytic, Chronic, B-Cell
D018442
Lymphoma, B-Cell, Marginal Zone
D008224
Lymphoma, Follicular
D020522
Lymphoma, Mantle-Cell
D008258
Waldenstrom Macroglobulinemia
D015463
Leukemia, Prolymphocytic
Ancestor Terms
ID
Term
D009370
Neoplasms by Histologic Type
D009369
Neoplasms
D006402
Hematologic Diseases
D006425
Hemic and Lymphatic Diseases
Browse Leaves
Not provided
Browse Branches
Not provided
Intervention Browse Module
MeSH Terms
ID
Term
C455861
pegfilgrastim
D000069283
Rituximab
D003520
Cyclophosphamide
Ancestor Terms
ID
Term
D058846
Antibodies, Monoclonal, Murine-Derived
D000911
Antibodies, Monoclonal
D000906
Antibodies
D007136
Immunoglobulins
Browse Leaves
Not provided
Browse Branches
Not provided
stage III grade 2 follicular lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage I mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
Waldenstrom macroglobulinemia
prolymphocytic leukemia
stage I marginal zone lymphoma
contiguous stage II adult diffuse small cleaved cell lymphoma
contiguous stage II grade 1 follicular lymphoma
contiguous stage II grade 2 follicular lymphoma
contiguous stage II mantle cell lymphoma
contiguous stage II marginal zone lymphoma
contiguous stage II small lymphocytic lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II mantle cell lymphoma
noncontiguous stage II marginal zone lymphoma
noncontiguous stage II small lymphocytic lymphoma
stage III marginal zone lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
refractory chronic lymphocytic leukemia
stage IV marginal zone lymphoma
N/A
Intervention Model
Single Group Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Neulasta
Rituximab
Biological
375 mg/m^2/day on Days 1, 4, 8, 11, 45, and 52.
R-HiCy
Rituxan
Cyclophosphamide
Drug
50 mg/kg/day on Days 15, 16, 17, and 18.
R-HiCy
Cytoxan
Cy
CTX
81
Participants
Title
Denominators
Categories
ParticipantsBG00081
Title
Measurements
<=18 years
BG0000
Between 18 and 65 years
BG00071
>=65 years
BG00010
Sex/Gender, Customized
Count of Participants
Participants
Title
Denominators
Categories
Female
ParticipantsBG00081
Title
Measurements
BG00017
Male
ParticipantsBG00081
Title
Measurements
BG00059
Unknown
ParticipantsBG00081
Title
Measurements
BG0005
Race and Ethnicity Not Collected
Race and Ethnicity were not collected from any participant.
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0000
OG00081
Title
Denominators
Categories
Neutrophil
Title
Measurements
OG00015(11 to 32)
Platelet
Title
Measurements
OG00015(0 to 43)
Primary
Non-relapse Mortality
Number of participants who died for reasons related to protocol treatment.
Posted
Count of Participants
Participants
5 years
ID
Title
Description
OG000
R-HiCy
Rituximab (R) and high-dose cyclophosphamide (HiCy) with pegfilgrastim support.
Pegfilgrastim: 6 mg SQ 24-48 hours after last dose of cyclophosphamide.
Rituximab: 375 mg/m^2/day on Days 1, 4, 8, 11, 45, and 52.
Cyclophosphamide: 50 mg/kg/day on Days 15, 16, 17, and 18.
Units
Counts
Participants
OG00081
Title
Denominators
Categories
Title
Measurements
OG0000
Primary
Event-free Survival
Percentage of participants alive without disease relapse.
Participants were split into two populations for this outcome only: mantle-cell lymphoma and other low-grade B-cell tumors.
Posted
Number
percentage of participants
5 years
ID
Title
Description
OG000
R-HiCy
Rituximab (R) and high-dose cyclophosphamide (HiCy) with pegfilgrastim support.
Pegfilgrastim: 6 mg SQ 24-48 hours after last dose of cyclophosphamide.
Rituximab: 375 mg/m^2/day on Days 1, 4, 8, 11, 45, and 52.
Cyclophosphamide: 50 mg/kg/day on Days 15, 16, 17, and 18.