Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Lymphoma, T-Cell, Cutaneous

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Peripheral T-cell Lymphoma

Cutaneous T-cell Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Denileukin diftitox

ONTAK (denileukin difitox, DAB389IL-2)

Francine Foss, M.D.

The purpose of this research study is to evaluate how effective ONTAK is in the treatment of cutaneous T-cell Lymphoma (CTCL) and determine whether the presence of a type of protein called CD25 on the cancer cells makes a difference in how the body responds to the treatment.

The hypothesis is that there is no difference in response rate for patients whose tumor cells are CD25 positive or negative.

Study of ONTAK® to Treat Cutaneous T-Cell Lymphoma (CTCL)

Open Label Study of ONTAK® (Denileukin Diftitox, DAB389IL-2) to Estimate Response in Cutaneous T-Cell Lymphoma (CTCL) According to CD25 Status

Tufts Medical Center

National Cancer Institute (NCI)

Ligand Pharmaceuticals

Eisai Inc.

Symptoms and General Pathology

Digestive System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Skin and Connective Tissue Diseases

Infections

Carcinoma

Carcinoma, Squamous Cell

Neoplasm Metastasis

Stomach Neoplasms

Esophageal Neoplasms

Urinary Bladder Neoplasms

Melanoma

Carcinoma, Renal Cell

Carcinoma, Merkel Cell

Neoplasms, Second Primary

Neoplastic Processes

Stomach Cancer

Esophageal Cancer

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Merkel Cell Carcinoma

Anti-Infective Agents

Antibodies

Antibodies, Monoclonal

Aldesleukin

Immunomodulating Agents

Immunoglobulins

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

AU-007 (Q2w) will be administered as a monotherapy sequential ascending doses with each Dose Escalation Cohort

AU-007 (Q2w) will be administered at a fixed dose in combination with a single dose of aldesleukin with the initial AU-007 dose. The aldesleukin dose will be escalated with each Dose Escalation Cohort

AU-007 will be administered at a fixed dose in combination with a aldesleukin, both administered Q2w. The aldesleukin dose will be escalated with each Dose Escalation Cohort

AU-007

John Powderly, MD

Meredith McKean

George Blumenschein

Drew Rasco

Siwen Hu-Lieskovan

Paul DeSouza

Elizabeth Ahern

Andrew Weickhardt

Andrew Haydon, MD

Catherine Oakman

James Vasselli, MD

This is a first in human, open-label, multi-center Phase 1 / 2 study to evaluate the safety, tolerability, and initial efficacy of AU-007 in patients with advanced solid tumors. AU-007 will be administered either as a monotherapy, or in combination with a single loading dose of aldesleukin, or with both AU-007 and aldesleukin given every 2 weeks (Q2w)

This is a first in human, multicenter, open-label Phase 1-2 study evaluating the safety, tolerability, and initial efficacy of AU-007 with or without aldesleukin, in patients with unresectable locally advanced or metastatic cancer. Patients must either be ineligible for or have progressed on prior standard of care therapy. Phase 1 consists of 3 escalation Arms, each starting with a single 1+2 escalation cohort followed by 3+3 escalation cohorts to define the recommended Phase 2 dose (RP2D) or maximum tolerated dose (MTD). The study begins in Arm A evaluating escalating doses of AU-007 (Q2w) in sequential escalation cohorts to define the recommended Phase 2 dose (RP2D) or maximum tolerated dose (MTD). In Arm B, AU-007 (Q2w) is evaluated in combination with a single dose of aldesleukin given with the first AU-007 dose. AU-007 is administered at a fixed dose (Q2w) with an escalating single aldesleukin dose in sequential escalation cohorts. In Arm C, AU-007 is evaluated in combination with aldesleukin both given Q2w. AU-007 will be administered at a fixed dose with an escalating dose of aldesleukin in each sequential Arm C escalation cohort. The Phase 2, cohort expansion portion of the study consists of three expansion Arms evaluating the initial efficacy of the RP2D from corresponding dose escalation Arms A, B, and C in selected solid tumor types. Initially, melanoma and renal cell cancer will be evaluated in each Arm. Other eligible cancers include but not limited to Merkel Cell Carcinoma, non-small cell lung cancer and urothelial cancer.

Study of AU-007, A Monoclonal Antibody That Binds to IL-2 and Inhibits IL-2Rα Binding, in Patients With Unresectable Locally Advanced or Metastatic Cancer

A Phase 1/2, First-in-Human, Open Label, Dose Escalation and Expansion Study of AU-007, A Monoclonal Antibody That Binds to IL-2 and Inhibits IL-2Rα Binding, in Patients With Unresectable Locally Advanced or Metastatic Cancer

Measured by the frequency of DLTs (Dose limiting Toxicity) and safety profile

With AU-007 alone or in combination with aldesleukin measured by PK, PD, and Biomarkers

The AUC of AU-007 will be measured at different timepoints after AU-007 administration

The Cmax of AU-007 will be measured at different timepoints after AU-007 administration

The Tmax of AU-007 will be measured at different timepoints after AU-007 administration

The T1/2 of AU-007 will be measured at different timepoints after AU-007 administration

Assessed by summarizing the number of patients who develop detectable anti-drug antibodies (ADAs) at different timepoints after AU-007 alone or in combination with aldesleukin

Clinical anti-tumor activity will be evaluated using conventional Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and modified RECIST v1.1.

Aulos Bioscience, Inc.

Leukemia

Leukemia, T-Cell

Leukemia-Lymphoma, Adult T-Cell

Hematologic Diseases

Leukemia, Lymphoid

Adult T-cell Leukemia/lymphoma

Leukemia, T-cell, Chronic

Antirheumatic Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Antibodies, Blocking

Immunotoxins

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Administer cycle 1 with Fludarabine and Cyclophosphamide (FC) alone. Two weeks after starting cycle 1, begin up to 6 cycles of FC plus LMB-2 at minimum 20-day intervals.

Begin with 30 mcg/Kg intravenous (IV) on days 3, 5 and 7. Escalate to 40 mcg/Kg if dose limiting toxicity (DLT) in 0/3 or 1/6 at 30 mcg/Kg. Continue at 40 mcg/Kg if 0-1 of 6 have DLT at 40 mcg/Kg.

LMB-2

Days 1-3:

Patients 1-7, 10-14, and \>18:25mg/m\^2/day Patients 8 - 9:30 mg/m\^2/day Patients 15- 17:20 mg/m\^2/day

Days 1-3:

Patients 1-7, 10 -14, and \>18:250 mg/m\^2/day Patients 8 - 9:300 mg/m\^2/day Patients 15-17:200 mg/m\^2/day

Robert J Kreitman, M.D.

BACKGROUND:

* Cluster of differentiation 25 (CD25) (p55, Tac or interleukin 2 receptor (IL2R) alpha) is strongly expressed in virtually 100% of patients with adult T-cell leukemia/lymphoma (ATL), a highly aggressive human T-lymphotropic virus type 1 (HTLV-1) related malignancy responding poorly to chemotherapy.
* In ATL, the humanized anti-CD25 monoclonal antibody (Mab) daclizumab produced 13-14% responses, and the anti-CD52 Mab Alemtuzumab (Campath-1H) produced response lasting greater than 2 months in 30% of 23 patients.
* LMB-2 is an anti-CD25 recombinant immunotoxin containing variable domains of murine MAb anti-Tac and truncated Pseudomonas exotoxin.
* In a phase I trial at National Cancer Institute (NCI), the maximum tolerated dose (MTD) of LMB-2 was 40 microg/Kg intravenous (IV) given every other day for 3 doses (every other day (QOD) times 3). LMB-2 induced greater than 90% tumor reduction rapidly in all 3 ATL patients on protocol, but achieved only 1 partial response due to rapid tumor progression and/or immunogenicity.
* In preclinical models, response from recombinant immunotoxins is limited by high concentrations of soluble receptor in the blood and especially in the interstitial space of the tumor. Synergism was observed with chemotherapy and immunotoxins, possibly due to reduction of soluble receptor in tumor interstitium.

OBJECTIVES:

-To determine, in nonrandomized fashion, if after verifying its safety, fludarabine and cyclophosphamide (FC) prior to LMB2 for ATL can result in low immunogenicity and a rate of major response lasting greater than 2 months, which may be an improvement over that demonstrated previously from Alemtuzumab (CAMPATH).

Secondary objectives:

* To determine the effect of 1 cycle of FC alone in ATL.
* To examine progression-free and overall survival in ATL after FC/LMB-2.
* Evaluate pharmacokinetics, toxicity, and monitor soluble CD25 and other tumor marker levels in the serum.
* To study the effects of LMB-2 plus FC on normal B- and T-cell subsets by fluorescence-activated cell sorting (FACS).

ELIGIBILITY:

* CD25 plus ATL, untreated or with prior therapy
* Eastern Cooperative Oncology Group (ECOG) 0-2, absolute neutrophil count (ANC), platelets and albumin at least 1000, 75,000, and 3.0.

DESIGN:

* Fludarabine 25 mg/m(2) IV days 1-3
* Cyclophosphamide 250 mg/m(2) IV days 1-3
* LMB-2 30-40 micro g/Kg IV days 3, 5 and 7.
* LMB-2 dose: Begin with 30 microg/Kg times 3. Escalate to 40 microg/Kg if dose limiting toxicity (DLT) in 0/3 or 1/6 at 30 microg/Kg. Continue at 40 microg/Kg if 0-1 of 6 have DLT at 40 microg/Kg.
* Administer cycle 1 with FC alone. Two weeks after starting cycle 1, begin up to 6 cycles of FC plus LMB-2 at minimum 20-day intervals.
* Accrual goals: 29-37 patients, which includes 4 replacements....

BACKGROUND:

* Cluster of differentiation 25 (CD25) (p55, Tac or interleukin receptor 2 (IL2Ra) is strongly expressed in virtually 100 % of patients with adult T-cell leukemia/lymphoma (ATL), a highly aggressive human T-lymphotropic virus type 1 (HTLV-1) related malignancy responding poorly to chemotherapy.
* In adult T-cell leukemia (ATL), the humanized anti-CD25 monoclonal antibody (Mab) daclizumab produced 13-14 % responses, and the anti-CD52 Mab Alemtuzumab (Campath- 1H) produced response lasting \> 8 weeks in of 30 % of 23 patients.
* LMB-2 is an anti-CD25 recombinant immunotoxin containing variable domains of murine MAb anti-Tac and truncated Pseudomonas exotoxin.
* In a phase I trial at National Cancer Institute (NCI), the maximum tolerated dose (MTD) of LMB-2 was 40 mcg/Kg dose intravenous (IV) given every other day for 3 doses (every other day (QOD) x3). LMB-2 induced \> 90 % tumor reduction rapidly in all 3 ATL patients on protocol, but achieved only 1 partial response due to rapid tumor progression and/or immunogenicity.
* In preclinical models, response from recombinant immunotoxins is limited by high concentrations of soluble receptor in the blood and especially in the interstitial space of the tumor. Synergism was observed with chemotherapy and immunotoxins, possibly due reduction of soluble receptor in tumor interstitium.

OBJECTIVES:

* To determine, in nonrandomized fashion, if after verifying its safety, fludarabine and cyclophosphamide (FC) prior to LMB2 for ATL can result in low immunogenicity and a rate of major response lasting \> 8 weeks which may be an improvement over that demonstrated previously from Alemtuzumab (CAMPATH).
* Secondary objectives

  * To determine the effect of 1 cycle of FC alone in ATL.
  * To examine progression-free and overall survival in ATL after FC/LMB-2.
  * Evaluate pharmacokinetics, toxicity, and monitor soluble CD25 and other tumor marker levels in the serum.
  * To study the effects of LMB-2 +FC on normal B- and T-cell subsets by FACS.

ELIGIBILITY:

* CD25+ ATL, untreated or with prior therapy, leukemic type without malignant masses \> 4 cm.
* Eastern Cooperative Oncology Group (ECOG) 0-2, absolute neutrophil count (ANC), platelets and albumin at least 1000, 75,000, and 3.0 respectively.

DESIGN:

* IV fludarabine and cyclophosphamide (FC) days 1-3 (doses listed respectively)
* Patients 1-7 and 10-14, and \>18: 25 and 250 mg/m\^2/day
* Patients 8-9: 30 and 300 mg/m\^2/day
* Patients 15-17: 20 and 200 mg/m\^2/day
* LMB-2 dose: Begin with 30 mcg/Kg IV on days 3,5 and 7. Escalate to 40 mcg/Kg if dose limiting toxicity (DLT) in 0/3 or 1/6 at 30 mcg/Kg. Continue at 40 mcg/Kg if 0-1 of 6 have DLT at 40 mcg/Kg.
* Administer cycle 1 with FC alone. Two weeks after starting cycle 1, begin up to 6 cycles of FC plus LMB-2 at minimum 20 day intervals.
* Accrual goals: 29-37 patients, which includes 4 replacements.

Phase II Trial of LMB-2, Fludarabine and Cyclophosphamide for Adult T-Cell Leukemia

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

Response is based on the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphoma and must last \>8 weeks to meet the primary endpoint of the study. Complete remission (CR) 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 definitely assignable to the lymphoma. Partial response is reduction by ≥50% of leukemia cell count or ≥50% reduction in the size of all measurable lesions, and no increase in size of any measurable or evaluable lesion or appearance of new lesion. Stable disease is neither a response nor progressive disease. Progressive disease is appearance of new lesions, or an increase of 50% or greater in the sum of the product of the perpendicular diameters of the measurable lesions or persistent (at least two determinations) doubling of the peripheral blood leukemic cell count.

The maximum analyte concentration in serum was reported using a cytotoxicity assay measuring the level of LMB-2 in the plasma and using purified LMB-2 as a standard curve.

PFS was determined by the Kaplan Meier method beginning at the on study date and continuing until progression or last follow-up without progression. Progressive disease is assessed by the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphoma, and is the appearance of new lesions, or an increase of 50% or greater in the sum of the product of the perpendicular diameters of the measurable lesions or persistent (at least two determinations) doubling of the peripheral blood leukemic cell count.

OS is the time between the first day of treatment to the day of disease progression. Progressive disease is assessed by the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphoma, and is the appearance of new lesions, or an increase of 50% or greater in the sum of the product of the perpendicular diameters of the measurable lesions or persistent (at least two determinations) doubling of the peripheral blood leukemic cell count.

Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). 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.

DLT is a grade II-IV LMB-2 or fludarabine and cyclophosphamide (FC)-related toxicity, except vascular leak syndrome, alopecia, grade II-III allergic reaction with asymptomatic bronchospasm or urticarial is considered DLT. Grade III aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, and fever are not considered DLT. Grade IV creatine phosphokinase associated with any other DLT or not resolving to \<grade II within 2 weeks is considered DLT. Hematologic toxicity is not considered DLT unless it fails to resolve to \<grade 2 or baseline by day 18 after cycle 1 or after day 25 after cycles 2-7. DLT from hepatotoxicity, creatine phosphokinase, and vascular leak syndrome is assumed from LMB-2, and hematologic toxicity from fludarabine and cyclophosphamide. Grade III proteinuria lasting \<2 weeks after the last dose of LMB-2 is not considered DLT, and needs to resolve to grade 0-2 prior to retreatment.

Tumor tissue, including lymph node or skin biopsies was examined and analysis performed by flow cytometry to determine the amount of cancer cells in the body by measuring proteins which fall off cancer cells and go into the blood.

AUC is a measure of the plasma concentration of drug over time. It is used to characterize drug absorption. Plasma levels were analyzed by cytotoxicity assay.

Peripheral blood was obtained and analyzed by flow cytometry.

Blood was drawn prior to each cycle of LMB-2 to determine if the level, \>75% neutralization of 1000ng/ml of LMB-2 of neutralizing antibodies is too high to give additional LMB-2. Analysis was performed by cytotoxicity assay.

Duration of response is defined as a response lasting for at least 4 weeks but \>8 weeks and is assessed by the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphoma. Complete remission (CR) 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 definitely assignable to the lymphoma. Partial response is reduction by ≥50% of leukemia cell count or ≥50% reduction in the size of all measurable lesions, and no increase in size of any measurable or evaluable lesion or appearance of new lesion.

Dilutions of patient plasma was tested by cytotoxicity assays to determine plasma clearance of LMB-2.The CL is a quantitative measure of the rate at which a drug substance is removed from the body.

Dilutions of patient plasma were tested by cytotoxicity assays to determine volume of distribution of LMB-2. Volume distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. This was measured during the first 24 hours after administration of the dose on cycle 2 day 1.

Dilutions of patient plasma was tested by cytotoxicity assays to determine half life. Plasma decay half-life is the time measured for the plasma concentration of the drug to decrease by one half.

Adverse events is assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). 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. Grade 3 (mild), Grade 4 (life threatening) and Grade 5 (death).

Adverse events is assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). 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.

Principal Investigator

Leukemic patients receiving LMB-2 and at least 25+250 mg/m\^2 fludarabine and cyclophosphamide; CF03-CF05, CF07-CF10, and CF12-CF14.

Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC

Patients CF01-CF02, CF06, CF11, and CF15-CF18. This is a mixture of patients who did not receive LMB-2, who had lymphoma-type adult T-cell leukemia, and who received 20+250 mg/m\^2 of fludarabine cyclophosphamide (FC).

All Other Patients

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

African American

Tabago, Black

Peruvian, Hispanic

American from Jamaica, Black

Jamaican, Black

Ethiopian, Black

Jamaican

Barbados, Black

American, from Ghana, Black

Race/Ethnicity, Customized

United States

Region of Enrollment

CHOP

EPOCH-C

C, ESHAP, PTX, Gem

Medi507, Ontak, HAT

CHOP, C

EPOCH-RS

None

Hydroxyurea

CHOP, Hydroxyurea

LSG-15, radiation

Prior treatments included cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP), these 4 agents with etoposide (EPOCH) and campath (C or alemtuzumab, together EPOCH-C), etoposide, methylprednisolone, cytarabine, and cisplatin (ESHAP), pralatrexate (PTX), gemcitabine (Gem), siplizumab (Medi507), denileukin diftitox (Ontak), daclizumab or humanized anti-Tac (HAT) and EPOCH with rituximab and siplizumab (EPOCH-RS). The LSG-15 regimen includes prednisone, adriamycin, carmustine, etoposide, carboplatin, and vinorelbine.

One participant was not evaluable. Participant withdrew due to inability to receive second cycle, which was the first cycle containing LMB-2.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of ONTAK® to Treat Cutaneous T-Cell Lymphoma (CTCL)	NCT00211198	Lymphoma, T-Cel...	ONTAK (denileuk...	18 Years -	Eisai Inc.
Study of AU-007, A Monoclonal Antibody That Binds to IL-2 and Inhibits IL-2Rα Binding, in Patients With Unresectable Locally Advanced or Metastatic Cancer	NCT05267626	Advanced Solid ... Metastatic Canc...	AU-007 Aldesleukin	18 Years -	Aulos Bioscience, Inc.
Phase II Trial of LMB-2, Fludarabine and Cyclophosphamide for Adult T-Cell Leukemia	NCT00924170	Adult T-Cell Le...	LMB-2 Fludarabine Cyclophosphamid...	18 Years - 100 Years	National Institutes of Health Clinical Center (CC)
Augmentation of Dendritic Cell-Based Vaccines in Melanoma Patients by Depletion of Regulatory T Cells in Stage IV Melanoma Patients	NCT00847106	Melanoma	Daclizumab Dendritic cells	18 Years - 75 Years	Radboud University Medical Center
Augmentation of Dendritic Cell-Based Vaccines in Melanoma Patients by Depletion of Regulatory T Cells in Stage IV Melanoma Patients	NCT00847106	Melanoma	Daclizumab Dendritic cells	18 Years - 75 Years	Radboud University Medical Center

Spots Global Cancer Trial Database for cd25

Every month we try and update this database with for cd25 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for cd25

Every month we try and update this database with for cd25 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for cd25 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.