Clinical trial NCT00003451: Interleukin-12 Followed by Interferon Alfa in Treating Patients With Advanced Cancer
Official title: Phase I Trial of Interleukin-12 Followed by Interferon-Alpha
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Myeloproliferative Disorders
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Precancerous Condition
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
monoclonal gammopathy of undetermined significance
recurrent adult Hodgkin lymphoma
isolated plasmacytoma of bone
extramedullary plasmacytoma
refractory multiple myeloma
Waldenström macroglobulinemia
stage III multiple myeloma
stage IV chronic lymphocytic leukemia
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
refractory chronic lymphocytic leukemia
unspecified adult solid tumor, protocol specific
chronic phase chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
meningeal chronic myelogenous leukemia
untreated adult acute lymphoblastic leukemia
untreated adult acute myeloid leukemia
adult acute myeloid leukemia in remission
adult acute lymphoblastic leukemia in remission
polycythemia vera
primary myelofibrosis
essential thrombocythemia
untreated hairy cell leukemia
progressive hairy cell leukemia, initial treatment
refractory hairy cell leukemia
chronic myelomonocytic leukemia
T-cell large granular lymphocyte leukemia
acute undifferentiated leukemia
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III adult Burkitt lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV adult Burkitt lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
stage III adult T-cell leukemia/lymphoma
stage IV adult T-cell leukemia/lymphoma
recurrent adult T-cell leukemia/lymphoma
secondary acute myeloid leukemia
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
prolymphocytic leukemia
primary systemic amyloidosis
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
recurrent mantle cell lymphoma
angioimmunoblastic T-cell lymphoma
anaplastic large cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
stage III small lymphocytic lymphoma
stage III marginal zone lymphoma
stage IV small lymphocytic lymphoma
stage IV marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
childhood myelodysplastic syndromes
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-09-13
Enrollment: 40
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Phase I trial to study the effectiveness of combining interleukin-12 and interferon alfa in treating patients who have residual, recurrent, or metastatic malignant melanoma or other advanced cancer that has not responded to standard therapy. Interleukin-12 may stimulate a person's white blood cells to kill cancer cells. Interferon alfa may interfere with the growth of the cancer cells. Combining interleukin-12 with interferon alfa may kill more cancer cells.

Detailed description: OBJECTIVES:

I. Determine the maximum tolerated dose of interferon alfa when preceded by a single dose of interleukin-12 in patients with recurrent or metastatic melanoma or other advanced malignancies.

OUTLINE: This is a dose-escalation study.

Cohorts of 3 patients receive interleukin-12 IV push on day 1, followed by escalating doses of interferon alfa by subcutaneous injection at 24, 48, 72, 96 and 120 hours. Courses repeat every 2 weeks for 6 months (12 courses total) in the absence of unacceptable toxicity and disease progression. Patients achieving partial response or stable disease at the completion of 6 months of therapy may receive additional courses of therapy for up to 24 months. Dose escalation of interferon alfa continues in subsequent cohorts in the absence of dose limiting toxicity (DLT). If 1 of 3 patients experiences DLT at a dose level, then 3 additional patients are entered at that dose level. If 2 of 6 patients experience DLT, then dose escalation stops. The maximum tolerated dose is defined as 1 level below that dose at which 2 or more of 6 patients experience DLT. Patients are followed every 3 months for 1 year and then every 6 months thereafter.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed residual, recurrent, or metastatic malignant melanoma or other advanced malignancies
* Must have failed standard curative and/or palliative therapies
* No brain or central nervous system metastases

PATIENT CHARACTERISTICS:

* Age: 13 and over
* Performance status: Karnofsky 70-100%
* Life expectancy: At least 12 weeks
* Absolute neutrophil count at least 1,500/mm3
* Platelet count at least 100,000/mm3 Hemoglobin at least 9 g/dL (may be posttransfusion or may receive erythropoietin)
* Bilirubin no greater than 1.5 times upper limit of normal (ULN)
* SGOT and SGPT no greater than 2 times ULN
* Creatinine no greater than 1.5 times ULN
* Creatinine clearance at least 60 mL/min
* Calcium no greater than 11 mg/dL (may receive agents to decrease calcium)
* No significant cardiovascular disease
* No cardiac arrhythmia requiring drug or device intervention
* No history of significant peripheral neuropathy
* No significant central nervous system disease
* HIV negative Hepatitis B surface antigen negative
* No concurrent serious infection requiring intravenous antibiotic therapy
* No clinically significant autoimmune disease (i.e., rheumatoid arthritis)
* No clinically significant gastrointestinal bleeding or uncontrolled peptic ulcer disease
* No history of inflammatory bowel disease
* No other major illness that substantially increases the risk associated with participation in this study
* Not pregnant or nursing Effective contraception required of all fertile patients

PRIOR CONCURRENT THERAPY:

* At least 4 weeks since prior biologic therapy
* At least 4 weeks since prior chemotherapy
* No concurrent systemic corticosteroids
* At least 2 weeks since prior local radiotherapy
* At least 2 weeks since surgery Other: At least 4 weeks since prior investigational drug

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital - Ohio State University
state: Ohio
Study officials:
affiliation: Ohio State University Comprehensive Cancer Center
name: William E. Carson, MD
role: STUDY_CHAIR
References: