Symptoms and General Pathology

All Conditions

Recurrence

Antineoplastic Agents

All Drugs and Chemicals

Denileukin diftitox

Given at a dose of 9 or 18mcg/kg/day by intravenous infusion over 30 to 60 minutes for 5 consecutive days every 21 days for 8 cycles.

Denileukin diftitox (ONTAK)

Gary Palmer, MD

The purpose of this study is to provide continued therapy with Denileukin diftitox (ONTAK) to patients who are currently on therapy and who have no other suitable treatment options, where therapy is requested by their physician.

The Access Program will be provided as long as appropriate according to the judgment of the provider. If Denileukin diftitox (ONTAK) becomes commercially available without restriction, then the access program will be discontinued.

Access Program With Denileukin Diftitox for the Treatment of Patients Currently Receiving Treatment With Commercially Available (Ontak)

Eisai Inc.

Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Denileukin Diftitox (Ontak) administered Post Autologous Transplantation.

After receiving their stem cell transplant on Day 0, participants will receive study agent via a 30 minute infusion. Participants will also receive a 30 minute infusion of study agent on Day 21.

Follow-up visits for clinical assessment, blood draws for routine clinical laboratory studies and for immuno-correlative studies will also take place on days 42, 90, 180 and 360.

Denileukin Diftitox (Ontak)

Zaid Al-Kadhimi, M.D.

The primary goal of this study is to determine the feasibility and safety of giving two doses of denileukin diftitox (DD) at days 0 and 21 post autologous stem cell transplantation in a dose escalation fashion. Secondary goals include evaluating the the effect of DD on the number and percentage of T-regs in the peripheral blood post transplant at each dose level, the effect of DD on T cell (CD4/CD8) reconstitution post transplant at each dose level and determining the time to engraftment: absolute neutrophil count (\>0.5 x 10\^9/L for 3 consecutive days), and platelet (\>20X 10\^9/L for 3 consecutive days).

The hypothesis for the study is based on the ability of DD to deplete T-regs and subsequently enhance the immune reconstitution and reverse post transplant lymphopenia. This may indirectly enhance the efficacy of autologous transplantation and reduce disease relapse.

Dose Escalation Trial of Denileukin Diftitox (Ontak) Post Autologous Transplantation

Phase I Dose Escalation Trial of Denileukin Diftitox (Ontak) Post Autologous Transplantation.

After drug infusion, participants will be closely monitored for at least 4 hours for side effects

During hospitalization stay (approximately 2 weeks), participants will receive injections of G-CSF on a daily basis starting on Day 6 and ending when white blood cells have engrafted. Participants usually remain hospitalized until engraftment.

Barbara Ann Karmanos Cancer Institute

Principal Investigator

Denileukin Diftitox (Ontak) administered Post Autologous Transplantation.

Denileukin Diftitox (Ontak) : After receiving their stem cell transplant on Day 0, participants will receive study agent via a 30 minute infusion. Participants will also receive a 30 minute infusion of study agent on Day 21.

Follow-up visits for clinical assessment, blood draws for routine clinical laboratory studies and for immuno-correlative studies will also take place on days 42, 90, 180 and 360.

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Analysis was not completed due to the small number of patients accrued and drugs were unavailable.

Assess Toxicities of Giving Two Doses of Ontak at Days 0 and 21 Post Autologous Stem Cell Transplantation in a Dose Escalation Fashion.

To Evaluate the Effect of Ontak on the Number and Percentage of Regulatory T Cells in the Peripheral Blood Post Transplant at Each Dose Level.

To Evaluate the Effect of Ontak on T Cell CD4/CD8 Reconstitution Post Transplant at Each Dose.

To Evaluate the Effect of Ontak on Engraftment of Neutrophils and Platelets Post Transplant at Each Dose.

Overall Study

Infections

Leukemia

Leukemia, T-Cell

Virus Diseases

Leukemia-Lymphoma, Adult T-Cell

Lymphoma

Leukemia, Lymphoid

Lymphatic Diseases

Adult T-cell Leukemia/lymphoma

Human T-cell Leukemia Virus Type 1

Leukemia, T-cell, Chronic

Lymphosarcoma

Immunotoxins

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.

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

Denileukin diftitox (Ontak)

Thomas A Waldmann, M.D.

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.

Background:

Adult T-Cell Leukemia is a lymphoproliferative disorder characterized by the presence of CD4/CD25 expressing T cells (IL-2R expressing) in the peripheral blood, in lymphoid and other tissues.

Denileukin diftitox is a genetically engineered fusion protein combining the enzymatically active domains of diphtheria toxin (DT) and the full length sequence of interleukin-2 (IL-2) that targets IL-2 expressing malignancies.

Denileukin diftitox interacts with the IL-2 R on the cell surface, is internalized via endocytosis, and inhibits cellular protein synthesis resulting in cell death within hours to days.

Objective:

Determine the clinical response to Denileukin diftitox (Ontak) of patients with adult T-cell leukemia (ATL).

Define the safety of Denileukin diftitox in patients who have ATL.

Eligibility:

Patients with chronic, lymphomatous and acute forms of ATL.

Patients must be human T-cell lymphotropic virus type I (HTLV1) positive.

Design:

Patients will be treated with 9mcg/kg/d of Denileukin diftitox for five days, on an every two week schedule.

Tumor response will be evaluated after two cycles of treatment. Stable or responding patients will continue treatment with evaluations every four cycles of treatment. Patients will be treated for two cycles beyond a complete remission.

The trial uses an optimal 2 stage design targeting for a true response proportion greater than 30%. Nine patients will be treated initially with expansion to 29 patients if a response is seen in one of the initial nine patients treated. If no response is seen at the 9 mcg/kg/d dose an additional 9 patients will be treated at a dose of 18 mcg/kg/d with expansion to 29 patients at this dose level if a response is seen. A stopping rule for excessive toxicity will be incorporated.

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

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

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.

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Access Program With Denileukin Diftitox for the Treatment of Patients Currently Receiving Treatment With Commercially Available (Ontak)	NCT01432483	Cancer	Denileukin dift...	-	Eisai Inc.
Access Program With Denileukin Diftitox for the Treatment of Patients Currently Receiving Treatment With Commercially Available (Ontak)	NCT01432483	Cancer	Denileukin dift...	-	Eisai Inc.
Dose Escalation Trial of Denileukin Diftitox (Ontak) Post Autologous Transplantation	NCT01251952	Multiple Myelom...	Denileukin Dift...	18 Years - 70 Years	Barbara Ann Karmanos Cancer Institute
Phase II Study of the Efficacy and Toxicity of Ontak(Registered Trademark) (Denileukin Diftitox) in the Therapy of Adult T-Cell Leukemia	NCT00117845	Leukemia, Adult...	Denileukin dift...	18 Years -	National Institutes of Health Clinical Center (CC)

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