Clinical trial NCT00004258: EMD 121974 in Treating Patients With Locally Advanced or Metastatic Cancer
Official title: A Phase I Trial of EMD 121974 in Patients With Advanced or Metastatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Myeloproliferative Disorders
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Precancerous/Nonmalignant Condition
Small Intestine Cancer
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
stage I cutaneous T-cell non-Hodgkin lymphoma
stage II cutaneous T-cell non-Hodgkin lymphoma
stage III cutaneous T-cell non-Hodgkin lymphoma
stage IV cutaneous T-cell non-Hodgkin lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
isolated plasmacytoma of bone
extramedullary plasmacytoma
refractory multiple myeloma
Waldenstrom macroglobulinemia
stage III multiple myeloma
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
refractory chronic lymphocytic leukemia
small intestine lymphoma
unspecified adult solid tumor, protocol specific
chronic phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
meningeal chronic myelogenous leukemia
untreated adult acute lymphoblastic leukemia
untreated adult acute myeloid leukemia
polycythemia vera
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
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
chronic idiopathic myelofibrosis
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
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-07-26
Enrollment: 40
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: RATIONALE: EMD 121974 may stop the growth of cancer by stopping blood flow to the tumor.

PURPOSE: Phase I trial to study the effectiveness of EMD 121974 in treating patients who have locally advanced or metastatic cancer.

Detailed description: OBJECTIVES: I. Determine the safety and tolerability of EMD 121974 in patients with advanced or metastatic cancer. II. Correlate various surrogate markers of antiangiogenic activity with EMD 121974 therapy including magnetic resonance imaging and PET scans, serum assays for various angiogenic and antiangiogenic factors, serum and urine markers of calcium metabolism, and tumor biopsies.

OUTLINE: This is a dose-escalation study. Patients receive EMD 121974 IV over 1 hour twice weekly for 4 weeks. Treatment continues for an additional course in the absence of unacceptable toxicity. Patients with stable or responding disease may continue therapy indefinitely past the 2 courses until disease progression. Cohorts of 3-6 patients receive escalating doses of EMD 121974 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicities. Patients are followed every 3 months for the first year, and then every 4 months thereafter until disease progression.

PROJECTED ACCRUAL: A total of 31-40 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically or cytologically confirmed locally advanced or metastatic cancer that is considered incurable and for which no standard curative therapy exists No primary CNS malignancies Measurable evidence of residual, recurrent, or metastatic disease No prior CNS metastases with residual abnormal findings on neuroradiologic studies Prior CNS metastases allowed provided at least 6 months from definitive therapy and a normal CT or MRI of the brain

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At least 3 months Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Hemoglobin at least 9 mg/dL (may be post transfusion) Platelet count at least 100,000/mm3 Hepatic: Bilirubin normal SGOT/SGPT no greater than 2.5 times upper limit of normal PT/PTT normal Renal: Creatinine no greater than 1.5 mg/dL Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No active infection requiring parenteral antibiotics No documented abnormal CNS exam with seizure disorder or major neuropsychiatric problems

PRIOR CONCURRENT THERAPY: Biologic therapy: At least 2 weeks since prior hematopoietic growth factor or cytokine therapy and recovered No concurrent immunotherapy Chemotherapy: At least 4 weeks since prior chemotherapy (at least 6 weeks since prior nitrosoureas or mitomycin) and recovered No concurrent chemotherapy Endocrine therapy: No concurrent corticosteroids except for steroid replacement therapy or chronic low dose (no greater than 10 mg/day oral prednisone) therapy for nonmalignant conditions No concurrent hormonal therapy except oral contraceptives or hormonal replacement therapy Radiotherapy: At least 2 weeks since prior radiotherapy and recovered No concurrent radiotherapy Surgery: At least 2 weeks since prior surgery and recovered Other: At least 4 weeks since other prior investigational drugs No concurrent oral or parenteral anticoagulants except anticoagulants for central venous catheters including low dose warfarin (1-2 mg/day) and/or heparin No concurrent oral COX-2 specific inhibitors (e.g., celecoxib or rofecoxib)

Primary outcomes:
measure: To evaluate the safety and tolerability of escalating doses of twice weekly EMD 121974 in patients with cancer.
timeFrame: enrollement through termination
Secondary outcomes:
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
Study officials:
affiliation: Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea
name: Michael S. Gordon, MD
role: STUDY_CHAIR
References: