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Rituximab and Cyclophosphamide Followed by Vaccine Therapy in Treating Patients With Relapsed Hodgkin Lymphoma

Primary Purpose

Lymphoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
KGEL vaccine
Filgrastim
Rituximab
Cyclophosphamide
Sponsored by
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring recurrent adult Hodgkin lymphoma

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically confirmed classical Hodgkin's lymphoma Relapsed disease with achievement of at least a partial response or a metabolic response to most recent salvage therapy No primary induction failure, defined as disease progression during or within 2 months after completion of first-line therapy PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-1 Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 1,000/mm^3 Platelet count ≥ 75,000/mm^3 Hepatic Bilirubin ≤ 2.0 mg/dL* NOTE: *Unless due to lymphoma or Gilbert's syndrome Renal Creatinine ≤ 2.0 mg/dL Cardiovascular Ejection fraction ≥ 45% by echocardiogram or MUGA Pulmonary DLCO ≥ 50% of predicted (corrected for alveolar volume) Immunologic No known HIV positivity No active infection requiring oral or IV antibiotics No autoimmune or other disease requiring long-term systemic steroids or other long-term immunosuppressants Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Able to tolerate high-dose therapy No other malignancy within the past 3 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior bone marrow transplantation Endocrine therapy Not specified Radiotherapy Concurrent radiotherapy for disease progression after high-dose cyclophosphamide allowed at the discretion of the principal investigator Surgery Not specified

Sites / Locations

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Immunotherapy

Arm Description

All participants received two days of rituximab, then four days of high-dose cyclophosphamide followed by filgrastim. Participants then received six doses of KGEL vaccine over 24 weeks interspersed with four additional doses of rituximab.

Outcomes

Primary Outcome Measures

Number of Participants With Grade 3-5 Adverse Events
Number of participants who experienced at least one grade 3-5 adverse event by CTCAE 3.0 that was attributed to protocol intervention.
Percentage of Participants With an Increase in Frequency of LMP2-specific CD8+ T Cells
Percentage of participants with an increase in frequency of LMP2-specific CD8+ T cells. Increase in frequency is defined as at least one order of magnitude higher than baseline measurement.

Secondary Outcome Measures

Survival
Median number of months that participants were alive (overall survival) and alive without disease relapse or new diagnosis of myelodysplasia or acute leukemia (event-free survival).
Days to Neutrophil and Platelet Engraftment
Median number of days to absolute neutrophil count (ANC) >= 500/mcL and platelet count >=20000/mcL.

Full Information

First Posted
August 22, 2005
Last Updated
February 7, 2019
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00134082
Brief Title
Rituximab and Cyclophosphamide Followed by Vaccine Therapy in Treating Patients With Relapsed Hodgkin Lymphoma
Official Title
Pilot Study of Rituximab, High Dose Cyclophosphamide, and GM-CSF Based Immunotherapy for Relapsed Hodgkin's Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
November 2005 (Actual)
Primary Completion Date
January 2013 (Actual)
Study Completion Date
January 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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. Vaccines made from another person's cancer cells may help the body build an effective immune response to kill cancer cells. Giving rituximab together with chemotherapy and vaccine therapy may kill more cancer cells PURPOSE: This phase I/II trial is studying how well giving rituximab together with cyclophosphamide and vaccine therapy works in treating patients with relapsed Hodgkin lymphoma.
Detailed Description
OBJECTIVES: Primary Determine the safety and tolerability of rituximab and high-dose cyclophosphamide followed by vaccine therapy comprising an allogeneic vaccine that expresses Hodgkin's tumor antigens and sargramostim (GM-CSF) (KGEL vaccine) as salvage therapy in patients with relapsed Hodgkin lymphoma. Determine the immunologic response to this vaccine in these patients. Secondary Determine the 3-year relapse-free and overall survival of patients treated with this regimen. Determine the patterns of cellular immune reconstitution in patients treated with this regimen. OUTLINE: This is an open-label study. Patients receive rituximab IV on days -10 and -7 and then on days 29, 36, 43, and 50 (weeks 4-7) and high-dose (transplant-dose) cyclophosphamide IV on days -3 to 0 without stem cell rescue. Patients receive filgrastim (G-CSF) subcutaneously once daily beginning on day 6 and continuing until blood counts recover. Patients also receive vaccine therapy comprising an allogeneic vaccine that expresses Hodgkin's tumor antigens and sargramostim (GM-CSF) (KGEL vaccine) intradermally on day 1, and weeks 4, 8, 12, 16, and 24. After completion of high-dose cyclophosphamide, patients are followed every 3 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: Approximately 25 patients will be accrued for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
recurrent adult Hodgkin lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Immunotherapy
Arm Type
Experimental
Arm Description
All participants received two days of rituximab, then four days of high-dose cyclophosphamide followed by filgrastim. Participants then received six doses of KGEL vaccine over 24 weeks interspersed with four additional doses of rituximab.
Intervention Type
Biological
Intervention Name(s)
KGEL vaccine
Intervention Description
Vaccine was administered at weeks 0, 4, 8, 12, 16, and 24 at a dose of 1 x 10^8 cells per dose. The first dose was given on Day +1.
Intervention Type
Biological
Intervention Name(s)
Filgrastim
Other Intervention Name(s)
G-CSF
Intervention Description
5 mcg/kg/day starting on Day +6 until ANC is >= 1000/mcL.
Intervention Type
Biological
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan
Intervention Description
375 mg/m^2/day on Days -10, -7, and at weeks 4, 5, 6, and 7.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
50 mg/kg/day on Day -3, -2, -1, and 0.
Primary Outcome Measure Information:
Title
Number of Participants With Grade 3-5 Adverse Events
Description
Number of participants who experienced at least one grade 3-5 adverse event by CTCAE 3.0 that was attributed to protocol intervention.
Time Frame
Up to 36 months
Title
Percentage of Participants With an Increase in Frequency of LMP2-specific CD8+ T Cells
Description
Percentage of participants with an increase in frequency of LMP2-specific CD8+ T cells. Increase in frequency is defined as at least one order of magnitude higher than baseline measurement.
Time Frame
Change from 3 months to 6 months
Secondary Outcome Measure Information:
Title
Survival
Description
Median number of months that participants were alive (overall survival) and alive without disease relapse or new diagnosis of myelodysplasia or acute leukemia (event-free survival).
Time Frame
Up to 6 years
Title
Days to Neutrophil and Platelet Engraftment
Description
Median number of days to absolute neutrophil count (ANC) >= 500/mcL and platelet count >=20000/mcL.
Time Frame
Up to 46 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed classical Hodgkin's lymphoma Relapsed disease with achievement of at least a partial response or a metabolic response to most recent salvage therapy No primary induction failure, defined as disease progression during or within 2 months after completion of first-line therapy PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-1 Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 1,000/mm^3 Platelet count ≥ 75,000/mm^3 Hepatic Bilirubin ≤ 2.0 mg/dL* NOTE: *Unless due to lymphoma or Gilbert's syndrome Renal Creatinine ≤ 2.0 mg/dL Cardiovascular Ejection fraction ≥ 45% by echocardiogram or MUGA Pulmonary DLCO ≥ 50% of predicted (corrected for alveolar volume) Immunologic No known HIV positivity No active infection requiring oral or IV antibiotics No autoimmune or other disease requiring long-term systemic steroids or other long-term immunosuppressants Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Able to tolerate high-dose therapy No other malignancy within the past 3 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior bone marrow transplantation Endocrine therapy Not specified Radiotherapy Concurrent radiotherapy for disease progression after high-dose cyclophosphamide allowed at the discretion of the principal investigator Surgery Not specified
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Ambinder, MD
Organizational Affiliation
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Official's Role
Study Chair
Facility Information:
Facility Name
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231-2410
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Rituximab and Cyclophosphamide Followed by Vaccine Therapy in Treating Patients With Relapsed Hodgkin Lymphoma

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