Lymphoma
Conditions
Keywords
recurrent adult Hodgkin lymphoma
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.
Interventions
BIOLOGICALKGEL vaccine
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.
BIOLOGICALFilgrastim
5 mcg/kg/day starting on Day +6 until ANC is \>= 1000/mcL.
BIOLOGICALRituximab
375 mg/m\^2/day on Days -10, -7, and at weeks 4, 5, 6, and 7.
DRUGCyclophosphamide
50 mg/kg/day on Day -3, -2, -1, and 0.
Sponsors
National Cancer Institute (NCI)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Grade 3-5 Adverse Events | Up to 36 months | 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 | Change from 3 months to 6 months | 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
| Measure | Time frame | Description |
|---|---|---|
| Survival | Up to 6 years | 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 | Up to 46 days | Median number of days to absolute neutrophil count (ANC) \>= 500/mcL and platelet count \>=20000/mcL. |
Countries
United States
Participant flow
Pre-assignment details
One participant was a screen failure.
Participants by arm
| Arm | Count |
|---|---|
| Immunotherapy 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.
KGEL vaccine: 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.
Filgrastim: 5 mcg/kg/day starting on Day +6 until ANC is \>= 1000/mcL.
Rituximab: 375 mg/m\^2/day on Days -10, -7, and at weeks 4, 5, 6, and 7.
Cyclophosphamide: 50 mg/kg/day on Day -3, -2, -1, and 0. | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Death | 1 |
Baseline characteristics
| Characteristic | Immunotherapy | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 1 Participants | — |
| Age, Categorical Between 18 and 65 years | 29 Participants | — |
| Age, Continuous | 39.5 years | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 30 Participants | — |
| Sex: Female, Male Female | 13 Participants | — |
| Sex: Female, Male Male | 17 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 30 |
| other Total, other adverse events | 30 / 30 |
| serious Total, serious adverse events | 15 / 30 |
Outcome results
Primary
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.
Time frame: Up to 36 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immunotherapy | Number of Participants With Grade 3-5 Adverse Events | 6 Participants |
Primary
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.
Time frame: Change from 3 months to 6 months
Population: Although the specimens were collected per protocol, they were not interpretable and therefore no data was collected to assess this outcome measure
Secondary
Days to Neutrophil and Platelet Engraftment
Median number of days to absolute neutrophil count (ANC) \>= 500/mcL and platelet count \>=20000/mcL.
Time frame: Up to 46 days
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Immunotherapy | Days to Neutrophil and Platelet Engraftment | Days until ANC >= 500mcL | 17 days |
| Immunotherapy | Days to Neutrophil and Platelet Engraftment | Days until Platelet Count >=20000/mcL | 21.5 days |
Secondary
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).
Time frame: Up to 6 years
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Immunotherapy | Survival | Overall survival | 31.5 months |
| Immunotherapy | Survival | Event-free survival | 24.1 months |