Leukemia, Adult T-Cell Clinical Trial
Official title:
Phase II Study of the Efficacy and Toxicity of Ontak (Denileukin Diftitox) in the Therapy of Adult T-Cell Leukemia
| Verified date | November 2019 |
| Source | National Institutes of Health Clinical Center (CC) |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Terminated |
| Enrollment | 17 |
| Est. completion date | June 30, 2013 |
| Est. primary completion date | December 31, 2011 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
- INCLUSION CRITERIA: 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. EXCLUSION CRITERIA: 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. |
| Country | Name | City | State |
|---|---|---|---|
| United States | National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland |
| Lead Sponsor | Collaborator |
|---|---|
| National Cancer Institute (NCI) |
United States,
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. — View Citation
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. — View Citation
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. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | Number of Participants With Serious and Non-Serious Adverse Events | Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v3.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. | Date treatment consent signed to date off study, approximately 72 months |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Terminated |
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Ruxolitinib for Adult T-Cell Leukemia
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