Clinical trial NCT00134082: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lymphoma
Keywords: recurrent adult Hodgkin lymphoma
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-08-24
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With Grade 3-5 Adverse Events
timeFrame: Up to 36 months
measure: Percentage of Participants With an Increase in Frequency of LMP2-specific CD8+ T Cells
timeFrame: Change from 3 months to 6 months
Secondary outcomes:
measure: Survival
timeFrame: Up to 6 years
measure: Days to Neutrophil and Platelet Engraftment
timeFrame: Up to 46 days
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Richard Ambinder, MD
role: STUDY_CHAIR
References: