Clinical trial NCT00010192: Rituximab Plus Interleukin-2 in Treating Patients With Hematologic Cancer
Official title: A Phase I Trial Of Rituximab And Interleukin-2
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: B-cell Adult Acute Lymphoblastic Leukemia
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Nodal Marginal Zone B-cell Lymphoma
Noncontiguous Stage II Adult Burkitt Lymphoma
Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma
Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma
Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma
Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma
Noncontiguous Stage II Adult Lymphoblastic Lymphoma
Noncontiguous Stage II Grade 1 Follicular Lymphoma
Noncontiguous Stage II Grade 2 Follicular Lymphoma
Noncontiguous Stage II Grade 3 Follicular Lymphoma
Noncontiguous Stage II Mantle Cell Lymphoma
Noncontiguous Stage II Marginal Zone Lymphoma
Noncontiguous Stage II Small Lymphocytic Lymphoma
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Small Lymphocytic Lymphoma
Splenic Marginal Zone Lymphoma
Stage III Adult Burkitt Lymphoma
Stage III Adult Diffuse Large Cell Lymphoma
Stage III Adult Diffuse Mixed Cell Lymphoma
Stage III Adult Diffuse Small Cleaved Cell Lymphoma
Stage III Adult Immunoblastic Large Cell Lymphoma
Stage III Adult Lymphoblastic Lymphoma
Stage III Grade 1 Follicular Lymphoma
Stage III Grade 2 Follicular Lymphoma
Stage III Grade 3 Follicular Lymphoma
Stage III Mantle Cell Lymphoma
Stage III Marginal Zone Lymphoma
Stage III Small Lymphocytic Lymphoma
Stage IV Adult Burkitt Lymphoma
Stage IV Adult Diffuse Large Cell Lymphoma
Stage IV Adult Diffuse Mixed Cell Lymphoma
Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
Stage IV Adult Immunoblastic Large Cell Lymphoma
Stage IV Adult Lymphoblastic Lymphoma
Stage IV Grade 1 Follicular Lymphoma
Stage IV Grade 2 Follicular Lymphoma
Stage IV Grade 3 Follicular Lymphoma
Stage IV Mantle Cell Lymphoma
Stage IV Marginal Zone Lymphoma
Stage IV Small Lymphocytic Lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Interleukin-2 may stimulate a person's white blood cells to kill cancer cells. Combining rituximab with interleukin-2 may kill more cancer cells. Phase I trial to study the effectiveness of rituximab plus interleukin-2 in treating patients who have hematologic cancer.

Detailed description: OBJECTIVES: Determine the dose-limiting toxicity of rituximab followed by low-dose and intermediate-dose pulse interleukin-2 (IL-2) in patients with CD20-positive B-cell lymphoid malignancy.

Determine the maximum tolerated dose of intermediate-dose pulse IL-2 in this patient population.

Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a dose-escalation study of intermediate-dose pulse aldesleukin.

Patients receive rituximab IV on days 1, 8, 15, and 22. Patients then receive low-dose aldesleukin subcutaneously (SC) on days 29-39, 43-53, 57-67, and 71-81, and intermediate-dose aldesleukin SC on days 40-42, 54-56, 68-70, and 82-84. Cohorts of 3-6 patients receive escalating doses of intermediate-dose pulse aldesleukin until the maximum tolerated dose (MTD) is reached. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 3 months for 1 year.

PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study within 1 year.

Eligibility criteria: Inclusion Criteria:

* Histologically or immunophenotypically proven CD20-positive B-cell lymphoproliferative disorder

  * Recurrent or progressive low-grade B-cell lymphoma with at least one prior chemotherapy regimen (may have included monoclonal antibody)
  * Relapsed intermediate-grade or high-grade B-cell lymphoma or B-lineage acute lymphoblastic leukemia and patient not a candidate for, refused, or failed prior hematopoietic stem cell transplantation
* No chronic lymphocytic leukemia or lymphoma with more than 5,000/mm3circulating lymphoma cells
* Measurable or evaluable disease
* Must have failed standard curative therapy
* No CNS or leptomeningeal metastasis
* Performance status - Karnofsky 70-100%
* Performance status - ECOG 0-1
* At least 4 months
* Absolute neutrophil count at least 1,000/mm\^3
* Hemoglobin at least 10 g/dL (transfusion allowed)
* Platelet count at least 50,000/mm\^3
* AST no greater than upper limit of normal (ULN)
* Bilirubin no greater than 1.5 times ULN
* Hepatitis B surface antigen negative
* Creatinine no greater than ULN
* No prior unstable coronary artery disease
* No New York Heart Association class III or IV congestive heart failure
* DLCO and FEV1 at least 50% of predicted
* HIV negative
* No other concurrent malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix
* No infection requiring IV antibiotic therapy within the past 4 weeks
* No other major illness that would preclude study
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* See Disease Characteristics
* Prior antibody therapy allowed
* Prior interleukin-2 or interferon alfa allowed
* See Disease Characteristics
* At least 4 weeks since prior chemotherapy
* At least 4 weeks since prior systemic corticosteroids
* At least 4 weeks since prior radiotherapy
* At least 4 weeks since prior surgery

Primary outcomes:
measure: MTD defined as the dose preceding that at which at least 2 of 6 patients experience DLT using NCI CTC version 2.0
timeFrame: 2 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
Study officials:
affiliation: Ohio State University
name: Pierluigi Porcu
role: PRINCIPAL_INVESTIGATOR
References: