RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase I trial to study the effectiveness of UCN-01 in treating patients with advanced cancer that has not responded to previous treatment..

Condition	Treatment or Intervention	Phase
Lymphoma Leukemia	Drug: UCN-01	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the toxicity profile, dose limiting toxicity, and maximum tolerated dose of UCN-01 administered as a 3, 2, or 1 hour infusion every 4 weeks for patients with advanced solid tumor malignancies and chronic lymphoproliferative disorders. II. Investigate the pharmacokinetics and cellular pharmacodynamics of UCN-01 administered on this schedule in these patients. III. Obtain preliminary evidence of the antitumor activity of UCN-01 in this patient population.

PROTOCOL OUTLINE: This is dose escalation study. Patients receive UCN-01 by intravenous infusions over 3, 2 or 1 hour(s) every 4 weeks. The first dose level is administered over 3 hours, the next dose level is administered over 2 hours, and the next and subsequent dose levels are administered over 1 hour. One patient is treated at each dose level until unacceptable toxicity is observed. An additional 2 patients are then entered at that dose level. If dose limiting toxicity (DLT) is experienced in 1 of 3 patients, 3 additional patients are accrued at that dose level. If 2 or more patients experience DLT, the maximum tolerated dose has been surpassed and a total of 6 patients must be treated at the previous dose level. If no patients develop DLT, the dose is escalated in successive cohorts of 3 patients per dose level. Patients are followed for 4 weeks after each drug administration before subsequent patients can be entered at the next higher dose level. Patients are followed for 2 months after their last dose of UCN-01.

PROJECTED ACCRUAL: Approximately 36 patients will be accrued into this study over 18 months.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed malignancy that is refractory to standard therapy or for which no standard therapy exists
• Low grade lymphoproliferative disorder defined as: Chronic lymphocytic leukemia/small lymphocytic lymphoma; Waldenstrom's macroglobulinemia; Follicular lymphoma (small cleaved, mixed, and large cell); Mantle cell lymphoma; Prolymphocytic leukemia (T and B type); Cutaneous T cell non-Hodgkin's lymphoma; Marginal zone lymphoma and variants; Hairy cell leukemia variants; MALT lymphomas
• Patients with low grade lymphoproliferative disorders must have received at least 1 or more treatment regimens and must not be eligible for potentially curative treatments (i.e., bone marrow transplantation)
• No HTLV-1 associated lymphomas, Burkitt's or small non-cleaved lymphomas, transplant related lymphoproliferative disorders, Hodgkin's disease, diffuse large cell lymphoma, or multiple myeloma
• No primary brain tumors or history of brain metastases

--Prior/Concurrent Therapy--

• Biologic therapy: At least 1 month since prior platelet or red blood cell transfusions
• Chemotherapy: At least 6 weeks since nitrosoureas or mitomycin; At least 4 weeks since other chemotherapy; No investigational or standard chemotherapy for at least 2 months after completion of last dose of UCN-01
• Endocrine therapy: Not specified
• Radiotherapy: At least 4 weeks since radiotherapy
• Surgery: At least 4 weeks since major surgery
• Other: No concurrent anticonvulsant medications

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-2
• Life expectancy: At least 12 weeks
• Hematopoietic: Absolute neutrophil count greater than 1,500/mm3; Platelet count greater than 100,000/mm3; Hemoglobin at least 8.0 g/dL
• Hepatic: Bilirubin no greater than 1.2 mg/dL; AST/ALT less than 2.5 times upper limit of normal
• Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance at least 60 mL/min
• Cardiovascular: No history of unstable or newly diagnosed angina pectoris; No myocardial infarction within the last 6 months; No New York Heart Association class II-IV congestive heart failure
• Neurologic: No grade 2 or greater peripheral neuropathy
• Pulmonary: No grade 2 or greater pulmonary toxicity (dyspnea on significant exertion)
• Other: HIV negative; No autoimmune hemolytic anemia; Must be able to have a central venous access catheter; No active infections requiring oral or intravenous antibiotics; No medical or psychiatric problems unrelated to the malignancy that may limit compliance with study, expose patient to undue risk, or confound toxicity assessment; Not pregnant or nursing; Adequate contraception is required of all fertile patients

Maryland
      Johns Hopkins Oncology Center, Baltimore,  Maryland,  21231,  United States

Study chairs or principal investigators

Ross C. Donehower,  Study Chair,  Johns Hopkins University   

Study ID Numbers:  CDR0000066221; JHOC-98012305; NCI-T97-0083
Record last reviewed:  May 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003289
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08