UCN-01 (7-Hydroxystaurosporine) to Treat Relapsed T-Cell Lymphomas

NCT00082017 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 04017304-C-0173
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine the effects of an experimental drug called UCN-01 (7-hydroxystaurosporine) on T-cell lymphomas. UCN-01 inhibits the growth of several different tumor cells, and, in laboratory studies, it has worked particularly well on tumor cells taken from patients with T cell lymphomas. Patients 9 years of age and older with T cell lymphoma that has relapsed or is not responding to chemotherapy may be eligible for this study. Candidates will be screened with a medical histories and physical examinations, blood and urine tests, electrocardiograms, chest x-rays, and computed tomography (CT) scans of the chest, abdomen and pelvis. Additional tests may be done if clinically indicated, such as positron emission tomography (PET) scans, bone marrow aspirations and biopsies, lumbar punctures (spinal taps) and CT's or magnetic resonance imaging (MRI) scans if there is evidence of central nervous system disease. Participants are given UCN-01 in 28-day treatment cycles. The drug is given by vein in a continuous 72-hour infusion on the first cycle and in 36-hour infusions on subsequent cycles. The total number of cycles patients receive depends on how well the tumor responds to the drug and how well the patient tolerates drug side effects. Patients who do well may receive treatment for up to 1 year. Patients whose disease worsens with treatment or who do not tolerate the therapy are taken off the study. Some or all of the screening tests are repeated periodically during the course of treatment to monitor safety and treatment response. X-rays and scans are done every other treatment cycle for the first 6 cycles and then, if the cancer is stable or improving, the interval between these imaging studies is lengthened to every 4 cycles. Patients whose tumors can be safely biopsied undergo this procedure before entering the study and 3 to 5 days after completing the first UCN-01 treatment. Biopsies requiring open surgery (e.g., in the chest or abdomen) are done only if absolutely necessary for medical care. Biopsy tissue, blood, and other fluids are analyzed for gene and protein studies related to lymphoma research.

Conditions

Lymphoma, Large-Cell, Ki-1; Lymphoma, T-Cell

Keywords

Protein Kinase Inhibition; Soluble Tac; Gene Expression Profiling; ALK Expression; Apoptosis; Lymphoma; Anaplastic Large Cell Lymphoma; ALCL; T-Cell Lymphoma

Outcome Measures

Primary Outcomes (3)

• Clinical Response Rate

  Clinical Response Rate is the percentage of participants with a response assessed by the International Workshop to Standardize Response Criteria. Complete response (CR) is complete disappearance of all detectable clinical and radiographic evidence of disease. Complete response unconfirmed (CRu) is per CR criteria except that if a residual node is \>1.5cm, it must have regressed by \>75%. Partial response (PR) is no increase in size of nodes, liver or spleen. Progressive disease (PD) is a greater than or equal to 50% increase from nadir. Details re: response criteria, see the protocol link module

  74.5 months

• Progression Free Survival (PFS)

  PFS is defined as the time interval from start of treatment to documented evidence of disease progression. Disease progression is assessed by the International Workshop to Standardize Response Criteria for non-Hodgkin's Lymphomas and is defined as a ≥50% increase from nadir in the sum of the products of the greatest diameters of any previously identified abnormal node for partial response's or non-responders or appearance of any new lesion during or at the end of therapy.

  3.6 months

• Overall Survival (OS)

  OS is defined as the date of on-study to the date of death from any cause or last follow up.

  55 months

Secondary Outcomes (1)

• Number of Participants With Adverse Events

  76 months

Other Outcomes (3)

• Effect of UCN-01 on Soluble TAC Cluster of Differentiation 25 (CD25)

  Day 3-5 after drug administration

• Evaluation of Mature T-cell Lymphoma Cells by Complementary Double-Stranded Deoxyribonucleic Acid (cDNA) Microarray

  Day 3-5 after drug administration

• Effect of UCN-01 on Anaplastic Lymphoma Kinase (ALK) Expression in ALCL

  Day 3-5 after drug administration

Study Arms (2)

UCN-01 for T-cell lymphomas - Cohort 1 - Every 28 days

EXPERIMENTAL

Cycle 1: 45 mg/m\^2/day continuous intravenous infusion 1 to 3 days (72 hours) for total dose of 135 mg/m\^2 Cycle 2: 45 mg/m\^2/day continuous intravenous infusion 1 to 2 days (36 hours) for total dose of 68 mg/m\^2; Repeat cycles every 28 days.

Drug: UCN-01 (7-hydroxystaurosporine)

UCN-01 for T-cell lymphomas - Cohort 2 -Every 21 days

EXPERIMENTAL

Cycle 1: 45 mg/m\^2/day continuous intravenous infusion 1 to 3 days (72 hours) for total dose of 135 mg/m\^2 Cycle 2: 45 mg/m\^2/day continuous intravenous infusion 1 to 2 days (36 hours) for total dose of 68 mg/m\^2; Repeat cycles every 21 days.

Drug: UCN-01 (7-hydroxystaurosporine)

Interventions

UCN-01 (7-hydroxystaurosporine) DRUG

UCN-01 for relapsed or refractory T-cell lymphomas - Cohort 1, Cycle 1: 45 mg/m\^2/day continuous intravenous infusion 1 to 3 days (72 hours) for total dose of 135 mg/m\^2 Cycle 2: 45 mg/m\^2/day continuous intravenous infusion 1 to 2 days (36 hours) for total dose of 68 mg/m\^2; Repeat cycles every 28 days. UCN-01 for relapsed or refractory T-cell lymphomas - Cohort 2, Cycle 1: 45 mg/m\^2/day continuous intravenous infusion 1 to 3 days (72 hours) for total dose of 135 mg/m\^2 Cycle 2: 45 mg/m\^2/day continuous intravenous infusion 1 to 2 days (36 hours) for total dose of 68 mg/m\^2; Repeat cycles every 21 days.

Also known as: UCN-01

UCN-01 for T-cell lymphomas - Cohort 1 - Every 28 days; UCN-01 for T-cell lymphomas - Cohort 2 -Every 21 days

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Relapsed or refractory systemic Anaplastic Large Cell Lymphoma (ALCL).
• Relapsed or refractory mature T-cell lymphoma to include peripheral T-cell lymphoma unspecified and the following "specified" mature T-cell lymphomas:
• Adult T-cell lymphoma; Extranodal natural killer (NK)/T-cell lymphoma,
• nasal type; Enteropathy-type T-cell lymphoma;
• Hepatosplenic T-cell lymphoma;
• Subcutaneous panniculitis-like T-cell lymphoma;
• Angioimmunoblastic T-cell lymphoma.
• All patients should have evaluable or measurable disease on entry to study.
• Histology confirmed by Laboratory of Pathology, National Cancer Institute (NCI).
• Performance Status Eastern Cooperative Oncology Group (ECOG) less than or equal to 2.
• Age 7 years or older.
• Creatinine less than or equal to 1.5 mg/dl or creatinine clearance greater than 50 ml/min for patients at least 18 years.
• Pediatric patients should have maximum serum creatinine by age as follows:
• Less than age 7 and less than or equal to age 10 may have a Maximum Serum Creatinine of 1.0 mg/dl
• Less than age10 and less than or equal to age 15 may have a Maximum Serum Creatinine of 1.2 mg/dl

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Stein H, Mason DY, Gerdes J, O'Connor N, Wainscoat J, Pallesen G, Gatter K, Falini B, Delsol G, Lemke H, et al. The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. Blood. 1985 Oct;66(4):848-58.

  PMID: 3876124 BACKGROUND

• Armitage JO, Weisenburger DD. New approach to classifying non-Hodgkin's lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin's Lymphoma Classification Project. J Clin Oncol. 1998 Aug;16(8):2780-95. doi: 10.1200/JCO.1998.16.8.2780.

  PMID: 9704731 BACKGROUND

• Falini B, Pileri S, Zinzani PL, Carbone A, Zagonel V, Wolf-Peeters C, Verhoef G, Menestrina F, Todeschini G, Paulli M, Lazzarino M, Giardini R, Aiello A, Foss HD, Araujo I, Fizzotti M, Pelicci PG, Flenghi L, Martelli MF, Santucci A. ALK+ lymphoma: clinico-pathological findings and outcome. Blood. 1999 Apr 15;93(8):2697-706.

  PMID: 10194450 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Lymphoma, Large-Cell, Anaplastic; Lymphoma, T-Cell; Lymphoma

Interventions

7-hydroxystaurosporine

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Wyndham Wilson, M.D.
• Organization: National Cancer Institute, National Institues of Health

wilsonw@mail.nih.gov

301-435-2415

Study Officials

• Wyndham Wilson, M.D.

  National Cancer Institute, National Institutes of Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Wyndham Wilson

Study Record Dates

• First Submitted: April 28, 2004
• First Posted: April 28, 2004
• Study Start: April 5, 2004
• Primary Completion: September 27, 2011
• Study Completion: September 27, 2011
• Last Updated: May 15, 2017
• Results First Posted: August 29, 2012

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)