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Lymphoma, Large-Cell, Ki-1Phase 2NCT00082017

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

A Phase 2 study testing UCN-01 (7-hydroxystaurosporine) in people with Lymphoma, Large-Cell, Ki-1 and Lymphoma, T-Cell, run by National Cancer Institute (NCI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Lymphoma, Large-Cell, Ki-1, Lymphoma, T-Cell
What is being tested?
UCN-01 (7-hydroxystaurosporine)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
5 Apr 2004to 27 Sep 2011
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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;
Show all 34Show fewer
  • 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
  • Age 15 years or older may have a Maximum Serum Creatinine of 1.5 mg/dl
  • Alternatively, pediatric patients should have a creatinine clearance of greater than 50 m1/min/1.73m^2.
  • Total bilirubin less than 1.5 x upper limit of normal (ULN) (patients with elevation of total bilirubin consistent with Gilbert's disease are eligible providing they have a normal direct bilirubin);
  • aspartate aminotransferase (AST) less than or equal to 2.5 x ULN;
  • absolute neutrophil count (ANC) greater than 500/mm^3;
  • and platelet greater than or equal to 50,000/mm^3;
  • unless hematological impairment due to organ involvement by lymphoma.
  • Provides signed informed consent.
  • Not pregnant or nursing. This drug has unknown effects in pregnancy and on young infants/children.
  • Human immunodeficiency virus (HIV) negative.
  • Willing to use contraception and continue for at least 8 weeks following the last treatment.
  • No active central nervous system (CNS) lymphoma.
  • Patients should not have received systemic cytotoxic chemotherapy within 3 weeks of study entry.
  • Have recovered from the toxic effects of prior therapy to a grade less than or equal to 1.
  • No history of diabetes mellitus requiring insulin treatment.
  • No symptomatic pulmonary disease.
  • No evidence of symptomatic cardiac disease (e.g. symptomatic congestive heart failure, unstable angina pectoris, exertional angina pectoris, cardiac arrhythmia).
  • Patients may not be concurrently receiving any other investigational agents.
  • Not a candidate for potentially curative (i.e. transplant) treatment at the time of study entry or the patient has a window of opportunity to receive UCN-01 before a transplant. Patients are required to have considered a transplant. If, having done this, they refuse it, decide against it or decide to wait, they would be eligible for this study.

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Phase II Study of UCN-01 in Relapsed or Refractory Systemic Anaplastic Large Cell and Mature T-Cell Lymphomas

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.

Read more

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.

Read the detailed description

Background:

  • UCN-01 (7-hydroxystaurosporine), a non-specific protein kinase C (PKC) inhibitor appears to have several mechanisms of action including protein kinase C (PKC) isoenzyme inhibition and cyclin dependent kinase activation and inhibition.
  • We have demonstrated that cell lines derived from T-cell lymphomas, including those with the t (2; 5) translocation, are very sensitive to UCN-01. The t (2; 5) translocation, associated with three quarters of cases of anaplastic large cell lymphomas (ALCL), is an oncogenic fusion protein - nucleophosmin-anaplastic lymphoma kinase (NPM-ALK).
  • Anaplastic lymphoma receptor tyrosine kinase (ALK) is one potential target for UCN-01 action, and anaplastic large cell lymphoma (ALCL) derived SUDHL-1 cells containing the NPM-ALK protein have been shown to be very sensitive to UCN-01.

Objectives:

  • To assess the clinical response to UCN-01 and progression-free and overall survival in patients with relapsed or refractory systemic Anaplastic Large Cell and other mature T-cell Lymphomas.
  • To assess the effect of UCN-01 on ALK expression in ALCL cells.
  • To assess the effect of UCN-01 on soluble tetrameric antibody complexes (TAC) (CD25).
  • To evaluate mature T-cell lymphoma malignant cells by complimentary deoxyribonucleic acid (cDNA) microarray.

Eligibility:

  • Relapsed or refractory systemic Anaplastic Large Cell Lymphoma (ALCL) with T or Null phenotype or relapsed or refractory mature T-cell lymphomas.
  • All patients should have evaluable or measurable disease on entry to study.
  • Requires systemic therapy
  • Performance Status Eastern Cooperative Oncology Group (ECOG) less than or equal to 2
  • Age 7 years or older
  • Human immunodeficiency virus (HIV) negative
  • Patients should not have received systemic cytotoxic chemotherapy within 3 weeks of study entry.

Design:

  • The study will be a Phase II study.
  • Patients will receive the first cycle of UCN-01 over 72 hours on days 1-3 and subsequent cycles over 36 hours. Patients with stable disease may receive UCN-01 for up to 1 year beyond achieving maximum response or stable disease, and restaging will be done every 2 cycles for the first 6 cycles and every 4 cycles thereafter.
  • Two sequential biopsies will be performed to investigate complimentary deoxyribonucleic acid (cDNA) expression by microarray. Soluble Tac (CD25) will be serially followed in patients.
  • For each of the two histologies, this study will be conducted using a Simon two-stage optimal design. Up to 37 patients will be treated.
Being tested
UCN-01 (7-hydroxystaurosporine)
Keywords
Protein Kinase Inhibition, Soluble Tac, Gene Expression Profiling, ALK Expression, Apoptosis, Lymphoma, Anaplastic Large Cell Lymphoma, ALCL, T-Cell Lymphoma
Medical subject headings
Lymphoma, Large-Cell, Anaplastic, Lymphoma, T-Cell, Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • UCN-01 (7-hydroxystaurosporine)Drug

    Also called UCN-01

    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.

Study groups in NCT00082017
Study groupRoleWhat they receive
UCN-01 for T-cell lymphomas - Cohort 1 - Every 28 daysExperimentalCycle 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.
Receives: Drug: UCN-01 (7-hydroxystaurosporine)
UCN-01 for T-cell lymphomas - Cohort 2 -Every 21 daysExperimentalCycle 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.
Receives: Drug: UCN-01 (7-hydroxystaurosporine)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 74.5 months

  2. 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.

    Measured: 3.6 months

  3. Overall Survival (OS)

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

    Measured: 55 months

Secondary outcomes (1)

  1. Number of Participants With Adverse Events

    Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

    Measured: 76 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Apr 2004 (estimated)
  2. Study start5 Apr 2004
  3. Primary completion27 Sep 2011
  4. Study completion27 Sep 2011

Why it stopped: IND was withdrawn by CTEP due to low accrual and cost of maintaining the IND.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00082017
Sponsor's protocol ID
040173
Other IDs
04-C-0173
Status last verified
May 2017
First submitted
28 Apr 2004
Last updated
15 May 2017
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 3876124

  • 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.

    PubMed 9704731

  • 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.

    PubMed 10194450

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing UCN-01 (7-hydroxystaurosporine) in people with Lymphoma, Large-Cell, Ki-1 and Lymphoma, T-Cell, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 34 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 15 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Aug 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinical Response Rate (time frame: 74.5 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00082017, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2017.

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