Phase II Study of the Efficacy and Toxicity of Ontak(Registered Trademark) (Denileukin Diftitox) in the Therapy of Adult T-Cell Leukemia

NCT00117845 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 05018505-C-0185
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

Adult T-cell leukemia (ATL) is and aggressive characterized by the presence of cluster of differentiation 4 (CD4)/cluster of differentiation 25 (CD25)-expressing T cells (interleukin-2 \[IL-2\]R expressing) in the peripheral blood and in lymphoid and other tissues. Denileukin diftitox (Ontak(Registered Trademark)) is a genetically engineered fusion protein that targets IL-2-expressing malignancies. Denileukin diftitox interacts with the IL-2R on the cell surface, is internalized via endocytosis, and inhibits cellular protein synthesis, resulting in cell death within hours to days. The objectives of this study are to determine the clinical response to Denileukin diftitox of patients with adult T-cell leukemia (ATL) and the safety of Denileukin diftitox in those patients. Eligible participants must be 18 years of age or older with chronic, lymphomatous and acute forms of ATL, and must be infected with human T-cell lymphotropic virus type I (HTLV1). Patients will be treated with 9 mcg/kg/d of Denileukin diftitox intravenously for 5 days every 2 weeks. Tumor response will be evaluated after two cycles of treatment. Stable or responding patients will continue treatment for a total of 12 months, with evaluations every four cycles of treatment. Patients will be treated for two cycles beyond a complete remission. The trial uses an optimal two-stage design targeting for a true response proportion of more than 30 percent. Nine patients will be treated initially, with expansion to 29 patients if a response is seen in 1 of the initial 9 patients treated. Treatment will be discontinued if a patient experiences serious side effects. A potential benefit is that a patient may undergo partial or complete remission. The research may not directly benefit participants, but the results may aid in the treatment of others.

Conditions

Leukemia, Adult T-Cell

Keywords

Denileukin Diftitox (Ontak); Recombinant Immunotoxin; Human T-Cell Lymphotropic Virus (HTLV1); CD25 Positive; IL-2R; ATL; Ontak; Adult T-Cell Leukemia; Lymphoproliferative Disorders

Outcome Measures

Primary Outcomes (1)

• Response Rate

  Response rate is based on the number of patients who achieve either a complete response (CR) or partial response (PR) to therapy. Complete response is complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease related symptoms if present before therapy and normalization of those biochemical abnormalities (for example LDH) definitely assignable to the lymphoma. Partial response is reduction by \>=50% of leukemia cell count or \>=50% reduction is the size of all measurable lesions, and no increase in size of any measurable or evaluable lesion or appearance of new lesion.

  up to 12 months

Secondary Outcomes (1)

• Number of Participants With Serious and Non-Serious Adverse Events

  Date treatment consent signed to date off study, approximately 72 months

Study Arms (1)

Denileukin Diftitox in ATL

EXPERIMENTAL

Denileukin Diftitox in adult T-cell leukemia (ATL) Patients will be treated with Denileukin Diftitox 9 mcg/kg/d intravenously for 5 days every 2 weeks.

Biological: Denileukin diftitox (Ontak)

Interventions

Denileukin diftitox (Ontak) BIOLOGICAL

Patients will be treated with Denileukin Diftitox 9 mcg/kg/d intravenously for 5 days every 2 weeks.

Denileukin Diftitox in ATL

Eligibility Criteria

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

You may qualify if:

• Patients must have serum antibodies directed to human T-lymphotropic virus type 1 (HTLV-I).
• All patients must have a histologically confirmed diagnosis of adult T-cell leukemia/lymphoma and more than 10% of the malignant cells must express cluster of differentiation 25 (CD25).
• All stages of Tac-expressing adult T cell leukemia except smoldering are eligible: patients with chronic, lymphomatous or acute adult T-cell leukemia (ATL) are eligible. (See appendix 2 for characteristics of patients with the various stages of ATL)
• Patients must have measurable disease. All patients with greater than 10% abnormal (i.e. TAC homogenous strongly expressing) peripheral blood mononuclear cells (PBMC) in the peripheral blood will be deemed to have measurable disease.
• The patient must have a granulocyte count of at least 1000/mm\^3 and a platelet count of greater than or equal to 50,000/mm\^3.
• Patients must have a creatinine of less than 2.0 mg/dl.
• Omission of cytotoxic chemotherapy for ATL for 3 weeks prior to entry into the trial is required. However, patients receiving corticosteroids will be eligible.
• Patients must have a life expectancy of greater than 2 months.
• Eligible patients must be greater than or equal to 18 years old. There is no upper age limit.
• Patients must have serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) value less than or equal to 2.5 times the upper limit of normal and bilirubin less than or equal to 3.0/dl. If a liver function test is judged to be elevated due to the underlying ATL, this parameter will be considered an unevaluable parameter for toxicity determinations.
• Patients must have a serum albumin greater than or equal to 2.5 g/dl
• Patients must be able to understand and sign an Informed Consent form.
• All patients must use adequate contraception during participation in this trial and for three months after completing therapy.

You may not qualify if:

• Patients with symptomatic leukemic meningitis will be excluded. However, patients that have both ATL and another HTLV-I-associated disease, tropical spastic paraparesis (TSP), will be included.
• Pregnant and nursing patients are not eligible for the study.
• Human immunodeficiency virus (HIV) positive patients are excluded from the study. Denileukin diftitox may produce a different pattern of toxicities in immunocompromised individuals.
• Patients with Smoldering ATL are excluded.
• Patients with serious intercurrent illnesses, past history of a myocardial infarction within 6 months or severe coronary artery disease
• Patients who previously received Denileukin diftitox are ineligible.

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)

• Yates AD, Morgan WT, Watkins WM. Linkage-specific alpha-D-galactosidases from Trichomonas foetus: characterisation of the blood-group B-destroying enzyme as a 1, 3-alpha-galactosidase and the blood-group P1-destroying enzyme as a 1, 4-alpha-galactosidase. FEBS Lett. 1975 Dec 15;60(2):281-5. doi: 10.1016/0014-5793(75)80731-9. No abstract available.

  PMID: 6322 BACKGROUND

• Uchiyama T, Yodoi J, Sagawa K, Takatsuki K, Uchino H. Adult T-cell leukemia: clinical and hematologic features of 16 cases. Blood. 1977 Sep;50(3):481-92. No abstract available.

  PMID: 301762 BACKGROUND

• Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD, Gallo RC. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7415-9. doi: 10.1073/pnas.77.12.7415.

  PMID: 6261256 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Leukemia-Lymphoma, Adult T-Cell; Lymphoproliferative Disorders

Interventions

denileukin diftitox

Condition Hierarchy (Ancestors)

Leukemia, T-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Thomas Waldmann, M.D.
• Organization: National Cancer Institute, National Institutes of Health

tawald@mail.nih.gov

301-496-6656

Study Officials

• Thomas A Waldmann, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 7, 2005
• First Posted: July 8, 2005
• Study Start: July 11, 2005
• Primary Completion: December 31, 2011
• Study Completion: June 30, 2013
• Last Updated: November 19, 2019
• Results First Posted: October 25, 2012

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)