Infections

All Conditions

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Pseudomonas Infections

Mesothelioma

Mesothelioma, Malignant

Sarcoidosis

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Mesothelial

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Pleural Neoplasms

Lung Diseases

Respiratory Tract Diseases

Malignant Mesothelioma

All Drugs and Chemicals

Antineoplastic Agents

Micronutrients

Hematinics

Vitamins

Antibodies

Antibodies, Monoclonal

Pemetrexed

Cisplatin

Immunoglobulins

Immunotoxins

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immunologic Factors

Folinic Acid

Folate

Vitamin B9

Assigned dose level of SS1(dsFv)PE38 on days 1, 3 \&amp; 5 of a 21 day cycle for 2 cycles

Multicycle SS1P

500 mg/m\^2 on day 1 of each 21 day cycle until disease progression

75 mg/m\^2 on day 1 of each 21 day cycle until disease progression

Patients 1 - 3 of single cycle cohort. 45 mcg/kg of SS1(dsFv)PE38 on 4 or 5 days (depending on dose level) of cycle 1 only.

Single cycle SS1P

Raffit Hassan, M.D.

Background:

Standard therapy for mesothelioma is a combination of the drugs pemetrexed and cisplatin. However, the benefits of this treatment are limited, and in most treated patients the disease continues to worsen.

SS1(dsFV)PE38 is a genetically engineered drug. It contains an antibody that binds to a certain protein on mesothelioma cells and a toxin (type of poison) made from a product of a bacterium called Pseudomonas aeruginosa. It is hoped that the antibody will attach to the cancer cells, allowing the toxin to enter and kill the cells.

Objectives:

To find out if SS1(dsFV)PE38, together with pemetrexed and cisplatin is safe and tolerable in patients with mesothelioma.

To determine the maximum tolerated dose of SS1(dsFV)PE38 (the highest dose that does not cause unacceptable side effects).

To see if SS1(dsFV)PE38 given with pemetrexed and cisplatin has any effect on patients tumors.

To learn how the body breaks down SS1(dsFV)PE38.

Eligibility:

Patients 18 years of age and older with epithelial pleural mesothelioma whose disease cannot be cured with surgery, and have not had prior treatment with chemotherapy.

Design:

Treatment with pemetrexed, cisplatin and SS1(dsFV)PE38 in two 21-day cycles as follows:

* Day 1 - Intravenous (through a vein) infusions of pemetrexed and cisplatin.
* Days 1 and 2 - Intravenous solution to prevent dehydration that might occur with SS1(dsFV)PE38.
* Days 1, 3 and 5 Intravenous infusion of SS1(dsFV)PE38. Small groups (3 to 6) of patients are given SS1(dsFV)PE38 at a certain dose level. If the first group experiences no significant side effects, the next group a higher dose. This continues in succeeding groups until the maximum tolerated study dose (highest dose that patients can be given safely) is determined.

Continuing standard treatment with additional cycles of pemetrexed and cisplatin.

Evaluations during the treatment period:

* Physical examination, including vital signs and body weight checks, and pregnancy test for women who can become pregnant.
* Questions about medications and side effects.
* Blood and urine tests.
* Disease evaluation with CT, chest X-ray, and possibly PET scans, lung function tests, pulse oximetry, performance of daily activities and quality-of-life questionnaires.

Post-treatment evaluations:

* Clinic visits at months 1, 3, 6, 12, 15, 18 and 21 for physical examination and disease assessment.
* End-of-study visit for blood tests, vital signs and weight measurements, disease assessment, electrocardiogram, pregnancy test for women who can become pregnant

Background:

SS1P (dsFv) PE38, is a recombinant immunotoxin targeting the tumor antigen mesothelin that is highly expressed in malignant mesothelioma. The maximum tolerated dose (MTD) of SS1 dsFv has been established in a phase I study.

Combination therapy with pemetrexed plus cisplatin is the standard first line therapy for malignant mesothelioma, but results in a median overall survival of only 12.1 months.

Combination of SS1(dsFv)PE38 with pemetrexed plus cisplatin could result in improved outcomes for patients with mesothelioma.

Objectives:

To determine the MTD of SS1(dsFv)PE38 that can be safely administered in combination with pemetrexed plus cisplatin in patients with mesothelioma.

To characterize the toxicity profile of SS1(dsFv)PE38.

To study the pharmacokinetics of SS1(dsFv)PE388.

To observe anti-tumor activity, if any of SS1(dsFv)PE38 in combination with pemetrexed plus cisplatin.

Eligibility:

Subjects with histologically confirmed epithelial pleural mesothelioma.

No prior radiotherapy (except palliative localized radiotherapy),systemic chemotherapy or biologic therapy for pleural mesothelioma.

Design:

This is a phase I dose-escalation study of SS1(dsFv)PE38 in combination with pemetrexed plus cisplatin.

The dose of pemetrexed plus cisplatin will be the standard dose approved for malignant mesothelioma. The dose of SS1(dsFv)PE38 will be escalated to find the safe dose in combination with pemetrexed plus cisplatin.

SS1(dsFv)PE38 will be administered concurrently with pemetrexed plus cisplatin in cycles one and two, and subjects will receive additional cycles of pemetrexed and cisplatin as per standard practice.

Patients will be assessed for response every 6 weeks.

An additional Single Cycle of SS1(dsFv)PE38 Cohort will involve up to 16 patients who will receive SS1(dsFv)PE38 administered for four or five doses during the first cycle concurrently with pemetrexed and cisplatin; subjects in this cohort will receive additional

cycles of pemetrexed and cisplatin as per standard practice

SS1(dsFV)PE38 Plus Pemetrexed and Cisplatin to Treat Malignant Pleural Mesothelioma

A Phase 1, Single Center, Dose-Escalation Study of SS1(dsFv)PE38 Administered Concurrently With Pemetrexed and Cisplatin in Subjects With Unresectable Malignant Epithelial Pleural Mesothelioma

list of adverse events and highest dose at which fewer than 2 subjects experienced DLT

proportion of subjects experiencing complete response, partial response or stable disease as a best overall response

National Cancer Institute (NCI)

Leukemia

Leukemia, Hairy Cell

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hairy Cell Leukemia

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Antipyretics

Analgesics

Antirheumatic Agents

Fibrinolytic Agents

Platelet Aggregation Inhibitors

Anti-Allergic Agents

Central Nervous System Depressants

Dermatologic Agents

Dexamethasone

Acetaminophen

Rituximab

Aspirin

Dexamethasone acetate

BB 1101

Diphenhydramine

Promethazine

Famotidine

Immunotoxin HA22

Antineoplastic Agents, Immunological

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase Inhibitors

Hypnotics and Sedatives

Anesthetics

Anesthetics, Local

Histamine H1 Antagonists

Histamine

Histamine phosphate

Histamine Antagonists

Neurotransmitter Agents

Antacids

Anti-Ulcer Agents

Histamine H2 Antagonists

Immunoconjugates

Arm 1 Moxetumomab Pasudotox-tdfk + Rituximab

Arm 1 and Arm 2 Moxetumomab Pasudotox-tdfk + Ruxience

Moxetumomab pasudotox-tdfk is administered at 30-40 ug/Kg intravenous (iv) over 30 min given on days 1, 3, 5 of each cycle.

Moxetumomab Pasudotox-tdfk

Rituximab will be administered at 375mg/m\^2 intravenous (iv), 50-400 mg/hour (hr). On cycle 1, Rituximab is given on day -2, on subsequent cycles, Rituximab is given on day 1.

Ruxience will be administered at 375mg/m\^2 intravenous (iv), 50-400 mg/hour (hr). On cycle 1, Ruxience is given on day -2, on subsequent cycles, Ruxience is given on day 1 (Delta)

Ruxience

12 mg Cycle 1, Day -2; Cycles 2-8, Day 1. Administer 0.5-2 hours before rituximab/Ruxience. If participant has previous reaction to rituximab/Ruxience, give 12mg. If participants tolerate rituximab/Ruxience without problems, may hold at discretion of provider. Pre-medications are given prior to rituximab/Ruxience on day 1.

650 mg Cycle 1, Day -2, Day 1, Day 3, Day 5. To be given 30-90 minutes prior to every moxetumomab pasudotox-tdfk infusion and recommended every 6 hours x 4 after the end of infusion; Cycles 2-8, Day 1, Day 3, Day 5. To be given 30-90 minutes prior to every moxetumomab pasudotox-tdfk infusion and recommended every 6 hours x 4 after the end of infusion. Pre-medications are given prior to rituximab/Ruxience on day 1.

25-50 mg Cycle 1, Day -2; Cycles 2-8, Day 1. Pre-medications are given prior to rituximab/Ruxience on day 1. May be given prior to moxetumomab pasudotox-tdfk at discretion of principal investigator.

20-40 mg Cycle 1, Day -2; Day 1, Day 3, Day 5. To be given 30-90 minutes prior to every moxetumomab pasudotox-tdfk infusion and is recommended every 12 hours x 2 after the end of infusion; Cycles 2-8, Day 1, Day 3, Day 5. To be given 30-90 minutes prior to every moxetumomab pasudotox-tdfk infusion and is recommended every 12 hours x 2 after the end of infusion. Pre-medications are given prior to rituximab/Ruxience on day 1.

81 mg Cycle 1, Days 1-8; Cycles 2-8, Days 1-8. Only if platelet counts ≥ 100 x 109/L.

Robert J Kreitman, M.D.

Background:

Hairy cell leukemia (HCL) is a rare, slow-growing blood cancer in which the bone marrow makes too many of certain white blood cells. The antibody Rituximab/Ruxience binds to a protein in cancerous white blood cells and is often used to treat HCL. Researchers want to see if combining it with the drug Moxetumomab pasudotox-tdfk (also called Lumoxiti) can fight HCL better.

Objective:

To test the safety of Moxetumomab pasudotox taken with Rituximab/Ruxience for people with HCL or HCL variant.

Eligibility:

People age 18 years and older with HCL or HCL variant that has not responded to standard therapy

Design:

Participants will be screened with:

Medical history

Physical exam

Blood, heart, and urine tests

Test of blood oxygen levels

Review of bone marrow. This can be from previous test results or a new sample.

Scans

Exercise test

Participants will get the study drugs in up to 8 cycles. A cycle will last about 28 days.

The study drugs will be given through a plastic tube in a vein.

In the first week of cycle 1, participants will have:

1 visit to get Rituximab or Ruxience for 7.5 hours

3 visits to get Lumoxiti for 30 minutes per infusion

In the first week of cycles 2-8, participants will have:

1. visit to get Rituximab/Ruxience for 2-4 hours and Lumoxiti for 30 minutes
2. visits to get Lumoxiti for 30 minutes per infusion

Participants will be asked to drink lots of water and take aspirin during the cycles. They will get drugs to minimize allergic reactions.

Participants will repeat screening tests at visits throughout the cycles and 1 follow-up visit. They may have an eye exam.

...

Background:

* Hairy cell leukemia (HCL) is an indolent cluster of differentiation-22 (CD22+) B-cell leukemia comprising 2% of all leukemias, or approximately 1200 of the 62,130 new cases of leukemia/year in the United States (US). HCL variant (HCLv), also CD22+, is 10-20% as common as HCL, but more common in the relapsed/refractory population due to its poor prognosis and response to standard purine analog chemotherapy. hairy cell leukemia variant (HCL-V) cells are cluster of Differentiation 25 (CD25)-negative and wild type for BRAF, so HCLv patients are not candidates for BRAF inhibitors. CD25+ classic-appearing HCL-cells that express unmutated IGHV4-34 (Immunoglobulin Heavy Variable 4-34) are wild-type for BRAF, remain brightly CD22 positive, and confer a poor prognosis when treated with chemotherapy.
* Moxetumomab pasudotox-tdfk is a recombinant immunotoxin containing a variable domain (Fv) fragment of an anti-CD22 monoclonal antibody and truncated Pseudomonas exotoxin, which kills CD22+ cells by binding to CD22 via the (Fv) fragment, and induction of apoptotic cell death catalytic inhibition of protein synthesis in the cytosol.
* Moxetumomab pasudotox-tdfk in phase 1 testing demonstrated a high complete response (CR) rate in patients with chemoresistant HCL, without dose-limiting toxicity (DLT), but with reversible grade 2 hemolytic uremic syndrome (HUS) not requiring plasmapheresis.
* Moxetumomab pasudotox-tdfk completed multicenter phase 3 testing in 80 patients, meeting its complete response (CR) endpoint, with 8.8% incidence each of capillary leak syndrome (CLS, grade 3-4 2.5%), and HUS (grade 3-4 6.3%), both reversible.
* Moxetumomab pasudotox-tdfk is the only known non-chemotherapy-containing regimen for HCL which can consistently eradicate minimal residual disease (MRD), and this is associated with prolonged CR durations. Recently, US Food and Drug Administration (FDA) has accepted the Biologics License Application (BLA) for moxetumomab pasudotox-tdfk as the treatment of adult patients with HCL.
* Patients who did not achieve CR, or CR with MRD, often made neutralizing antibodies to the bacterial-based toxin, and/or had collections of HCL cells not completely eradicated by Moxetumomab pasudotox-tdfk. Both issues may be addressed by the addition of anti-cluster of differentiation 20 (CD20) monoclonal antibody (Mab) rituximab or Ruxience to Moxetumomab pasudotox-tdfk.

Objective:

-To determine the safety and toxicity of Moxetumomab pasudotox-tdfk and rituximab/Ruxience used at the planned dose level, in patients with HCL and HCLv.

Eligibility:

* HCL or HCLv with at least 1 prior purine analog, and, for HCL patients with \>=2-years 1 month response, at least 1 other therapy.
* Need for treatment, either 1) absolute neutrophil count (ANC) \<1/nL, 2) hemoglobin (Hgb) \<10g/dL, 3) platelet (Plt) \<100/nL, 4) symptomatic splenomegaly, or enlarging HCL mass \> 2cm in short axis
* Serum creatinine \< 1.5 mg/dL, or creatinine clearance greater than or equal to 60 mL/min by Cockcroft-Gault equation, where creatinine clearance = (140-age)(kg weight)/(72 x Creatinine).
* No uncontrolled infection or cardiopulmonary dysfunction

Design:

* Phase I trial, two arm, non-randomized, dose escalation
* Administration:

  * Patients 1-13: Moxetumomab pasudotox-tdfk 30-40 mcg/kg intravenous (iv) over 30 min, Rituximab 375 mg/m\^2 iv, 50-400 mg/hr.
  * Patients 14-26: Moxetumomab pasudotox-tdfk 40 mcg/kg intravenous (iv) over 30 min, Ruxience 375 mg/m2 iv, 50-400 mg/hr
  * Rituximab or Ruxience day 1 (begin day -2 on cycle 1), Moxetumomab pasudotox-tdfk days 1, 3, and 5.
  * Patients will receive up to 4 cycles past documentation of CR without MRD, maximum 8.
  * To prevent renal toxicity and hypovolemia, patients will be encouraged to drink water gradually, approximately 0.5-1 cup/hour or 6L/day, not going \>3 hours without drinking from days 1 to 8 and to keep a hydration diary to record daily fluid consumption.
  * To prevent rituximab/Ruxience toxicity, patients will receive prophylactic dexamethasone orally 0.5- 2 hours before the 1st dose of rituximab, and before subsequent doses until rituximab/Ruxience infusion reactions are not seen. Patients will also receive diphenhydramine, famotidine, and acetaminophen.
  * Dexamethasone 4 mg orally (maximum 2 doses/day) will be given as needed to treat nausea or fever associated with Moxetumomab pasudotox-tdfk, which might prevent adequate water intake
* Statistical design:

  * Up to 26 patients are intended to be treated in the trial. While a total of 26 evaluable patients will be enrolled, the accrual ceiling will be set at 30 to include screen failures and inevaluable patients.

Moxetumomab Pasudotox-tdfk (Lumoxiti(TM)) and Either Rituximab (Rituxan(R)) or Ruxience for Relapsed Hairy Cell Leukemia

A Phase I Study of Moxetumomab Pasudotox-tdfk (Lumoxiti (TM)) and Either Rituximab (Rituxan (R)) or Ruxience for Relapsed Hairy Cell Leukemia

All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.

Dose limiting toxicity (DLT) is defined as all treatment related Grade 3-5 adverse events (AEs) occurring from the initiation of moxetumomab pasudotox-tdfk therapy to within 30 days after the last dose of moxetumomab pasudotox-tdfk treatment. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to adverse event.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). 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.

Recommended safe dose of moxetumomab pasudotox-tdfk is defined as the treatment of 10 participants with no more than 2 experiencing a dose-limiting toxicity (DLT). A DLT is defined as all treatment related Grade 3-5 adverse events (AEs) occurring from the initiation of moxetumomab pasudotox-tdfk therapy to within 30 days after the last dose of moxetumomab pasudotox-tdfk treatment assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to adverse event.

Recommended safe dose of rituximab/Ruxience is defined as the treatment of 10 participants with no more than 2 experiencing a dose-limiting toxicity (DLT). A DLT is defined as all treatment related Grade 3-5 adverse events (AEs) occurring from the initiation of moxetumomab pasudotox-tdfk therapy to within 30 days after the last dose of moxetumomab pasudotox-tdfk treatment assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to adverse event.

Number of participants whose cancer shrinks or disappears after treatment defined as minimal residual disease. MRD is no hairy cell leukemia (HCL) in the blood and bone marrow aspirate flow determined by immunohistochemistry (IHC) and flow cytometry of blood and bone marrow aspirate.

MRD-free is defined as participants with no hairy cell leukemia (HCL) in the blood and bone marrow aspirate flow determined by immunohistochemistry (IHC) and flow cytometry of blood and bone marrow aspirate.

DOR is defined as the time of initial response until documented tumor progression. Response was assessed by the and is defined as an increase in symptoms or \>25% decline in hematologic parameters related to disease, based on the judgement of the principal investigator. ≥50% increase in sum of products of perpendicular diameters of evaluable (\> 2cm) lymphadenopathy or appearance of new evaluable lymph nodes \> 2 cm short axis.

Principal Investigator

Participants with Relapsed/Refractory Hairy Cell Leukemia (HCL) or Hairy Cell Leukemia (HCLv)

Arm 1 Moxetumomab Pasudotox-tdfk + Rituximab

Dose escalation treatment with moxetumomab -pasudotox-tdfk and rituximab Moxetumomab pasudotox-tdfk is administered at 30 ug/Kg intravenous (iv) over 30 min given on days 1, 3, 5 of each cycle.

Rituximab will be administered at 375mg/m\^2 iv, 50-400 mg/hour (hr). On cycle 1, Rituximab is given on day -2, on subsequent cycles, Rituximab is given on day 1.

Moxetumomab - Dose Escalation 30 mcg/kg

Dose expansion; treatment with moxetumomab -pasudotox-tdfk and Ruxience

Arm 1 and Arm 2 Moxetumomab Pasudotox-tdfk + Ruxience

Moxetumomab pasudotox-tdfk is administered at 40 ug/Kg intravenous (iv) over 30 min given on days 1, 3, 5 of each cycle.

Ruxience will be administered at 375mg/m\^2 iv, 50-400 mg/hour (hr). On cycle 1, Ruxience is given on day -2, on subsequent cycles, Ruxience is given on day 1 (Delta)

Moxetumomab - Dose Expansion 40 mcg/kg

Participants with Relapsed/Refractory Hairy Cell Leukemia (HCL) or Hairy Cell Leukemia (HCLv)

Arm 1 Moxetumomab Pasudotox-tdfk + Rituximab

Dose escalation treatment with moxetumomab -pasudotox-tdfk and rituximab Moxetumomab pasudotox-tdfk is administered at 30-40 ug/Kg intravenous (iv) over 30 min given on days 1, 3, 5 of each cycle.

Rituximab will be administered at 375mg/m\^2 iv, 50-400 mg/hour (hr). On cycle 1, Rituximab is given on day -2, on subsequent cycles, Rituximab is given on day 1.

Dose expansion; treatment with moxetumomab -pasudotox-tdfk and Ruxience

Arm 1 and Arm 2 Moxetumomab Pasudotox-tdfk + Ruxience

Moxetumomab pasudotox-tdfk is administered at 30-40 ug/Kg intravenous (iv) over 30 min given on days 1, 3, 5 of each cycle.

Ruxience will be administered at 375mg/m\^2 iv, 50-400 mg/hour (hr). On cycle 1, Ruxience is given on day -2, on subsequent cycles, Ruxience is given on day 1 (Delta)

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Robert J. Kreitman

All participants in Group 1 and Group 2 who received at least one dose of Moxetumomab 30-40 mcg/kg.

All Participants

Recommended Safe Dose of Moxetumomab Pasudotox-tdfk

Recommended Safe Dose of Rituximab/Ruxience

Number of Participants Whose Cancer Shrinks or Disappears After Treatment

Number of Participants Who Are Minimal Residual Disease (MRD)-Free

Duration of Response (DOR)

Number of Participants With a Dose-limiting Toxicity (DLT)

Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

Overall Study

Leukemia, T-Cell

Virus Diseases

Leukemia-Lymphoma, Adult T-Cell

Lymphoma

Leukemia, Lymphoid

Adult T-cell Leukemia/lymphoma

Human T-cell Leukemia Virus Type 1

Leukemia, T-cell, Chronic

Lymphosarcoma

Denileukin diftitox

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
SS1(dsFV)PE38 Plus Pemetrexed and Cisplatin to Treat Malignant Pleural Mesothelioma	NCT01445392	Mesothelioma	Multicycle SS1P Pemetrexed Cisplatin Single cycle SS...	18 Years - 100 Years	National Institutes of Health Clinical Center (CC)
Moxetumomab Pasudotox-tdfk (Lumoxiti(TM)) and Either Rituximab (Rituxan(R)) or Ruxience for Relapsed Hairy Cell Leukemia	NCT03805932	Hairy Cell Leuk...	Moxetumomab Pas... Rituximab Ruxience Dexamethasone Acetaminophen Diphenhydramine Famotidine Aspirin	18 Years -	National Institutes of Health Clinical Center (CC)
SS1(dsFV)PE38 Plus Pemetrexed and Cisplatin to Treat Malignant Pleural Mesothelioma	NCT01445392	Mesothelioma	Multicycle SS1P Pemetrexed Cisplatin Single cycle SS...	18 Years - 100 Years	National Institutes of Health Clinical Center (CC)
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)

Spots Global Cancer Trial Database for recombinant immunotoxin