Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Nervous System Diseases

Symptoms and General Pathology

Rare Diseases

Lymphoma

Lymphoma, Large B-Cell, Diffuse

Unconsciousness

Central Nervous System Neoplasms

Nervous System Neoplasms

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

Lymphosarcoma

Primary Central Nervous System Lymphoma

B-cell Lymphoma

Antineoplastic Agents

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

All Drugs and Chemicals

Amino Acids

Methotrexate

Rituximab

Vincristine

Lenalidomide

Ibrutinib

Procarbazine

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Lenalidomide in association with R-MPV as a targeted induction treatment

Ibrutinib in association with R-MPV as a targeted induction treatment

Patients will receive 4 cycles of induction chemotherapy with R-MPV + Lenalidomide using the Maximum Tolerated Dose (MTD) of Lenalidomide and Ibrutinib as determined in the phase-Ib part of the study.

Patients will receive 4 cycles of induction chemotherapy with R-MPV + Ibrutinib, using the Maximum Tolerated Dose (MTD) of Lenalidomide and Ibrutinib as determined in the phase-Ib part of the study.

Carole SOUSSAIN, MD

LYNDA CORVI

Caroline DELETTE, MD

Jérôme PAILLASSA, MD

Sophie BERNARD, MD

Adrien CHAUCHET, MD

Anna SCHMITT, MD

Gandhi DAMAJ, MD

Gandhi DAMAJ, PhD

Cécile MOLUCON-CHABROT, MD

Guido AHLE, MD

Guido AHLE Guido AHLE, MD

Louise ROULIN, MD

Rémy Rémy GRESSIN, MD

Rémy GRESSIN, MD

Franck MORSCHHAUSER, PhD

Julie ABRAHAM, MD

ABRAHAM Julie, MD

Hervé GHESQUIERES, MD

Hervé GHESQUIERES, Phd

Olivier CHINOT, MD

Luc TAILLANDIER, PhD

Thomas GASTINNE, MD

Frédéric PEYRADE, MD

Agathe WAULTIER-RASCALOU, MD

Carole Soussain, MD

Lise WILLEMS, MD

Caroline HOUILLIER, MD

Vincent DELWAIL, MD

Thierry LAMY De La CHAPELLE, PhD

Thierry Thierry LAMY De La CHAPELLE, PhD

Fabrice JARDIN, PhD

Marie DE CHARETTE, MD

Luc-Mathieu FORNECKER, MD

Lucie Obéric, MD

Emmanuel GYAN, MD

Steven LE GOUILL, PhD

This study is to improve the first-line induction chemotherapy, by combining either Ibrutinib, or Lenalidomide, to a conventional immuno- chemotherapy of R-MPV type (Rituximab-Methotrexate-Procarbazine-Vincristine). This is a randomized Phase II trial, preceded by a dose escalation phase Ib. The objective of the phase Ib is to rule out any limiting toxicity of the new treatment associations, and to determine the recommended dose of Lenalidomide and Ibrutinib to be used in the phase II. In the phase II study, patients will receive 4 cycles of R-MPV + Lenalidomide or 4 cycles of R-MPV + Ibrutinib. The therapeutic response will be evaluated after the 2nd and the 4th cycle. Patients in good therapeutic response will proceed to the consolidation phase with Autologous Stem Cell Transplantation (ASCT).

The objective of this proposal is to test the feasibility and efficacy of two targeted induction chemotherapies obtained by adding either Lenalidomide or Ibrutinib to a standard Rituximab-High Dose (HD) Methotrexate (MTX) based induction chemotherapy regimen. The R-MPV regimen is chosen as the backbone chemotherapy because of its wide use with robust reproducible results and a good and manageable toxicity profile

LOC-R01 Study of Lenalidomide and Ibrutinib in Association With Rituximab-Methotrexate Procarbazine Vincristin (R-MPV)

LOC-R01: Randomized Phase IB/II Study of Escalating Doses of Lenalidomide and Ibrutinib in Association With R-MPV as a Targeted Induction Treatment for Patients Aged 18 to 60 (up to 65 for Phase II) With a Newly Diagnosed Primary Central Nervous System Lymphoma

Sponsor will share de-identified data sets generated under the project will be disseminated in accordance with Institut Curie policies.

Occurrence of a Dose Limiting Toxicity (DLT) during the first cycle of treatment for each treatment arm. The phase Ib is a 3+3 dose escalation design

The primary endpoint for the phase II part of the study is the Complete Response (CR) rate including unconfirmed CR (CR+uCR) at the end of the 4 cycles of induction therapy. Assessment of response will be based on the International Primary Central Nervous System Lymphoma Collaborative Group (IPCG)

Assessment of response will be based on the International Primary Central Nervous System Lymphoma Collaborative Group (IPCG)

Overall Survival (OS) will be calculated from the date of randomization to the date of death, whatever the cause. Patients alive at the date of last contact will be censored at this date.

Progression-Free Survival (PFS) will be calculated from the date of randomization to the date of progression or death (if the patient does not progress). Patients alive without progression at the date of last contact will be censored at this date

Toxicity of treatment induction or ASCT will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE 5.0) whenever possible and described by system organ class, preferred term

The percentage of patients who will receive ASCT will be presented

National Cancer Institute, France

Institut Curie

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Ovarian Cancer

Ovarian Epithelial Cancer

Docetaxel

Topotecan

Dennis R Scribner, JR, MD

Primary objective:

To estimate the overall clinical response rate (CR, PR, SD) of weekly docetaxel and weekly topotecan in women with recurrent platinum resistant ovarian or primary peritoneal cancer.

Secondary objectives:

To access the safety and tolerability of this novel combination chemotherapy regimen of weekly docetaxel and weekly topotecan in women with recurrent platinum resistant ovarian or primary peritoneal cancer

To estimate the progression free survival (PFS) and overall survival (OS) for women with recurrent platinum resistant ovarian or primary peritoneal cancer treated with this weekly docetaxel and weekly topotecan.

Each year more than 28,000 women are diagnosed with epithelial ovarian cancer (EOC). Over 70% of these women will present with advanced (stage III, IV) disease. The current treatment for newly diagnosed advanced EOC involves cytoreductive surgery followed by chemotherapy. The standard chemotherapy in the primary setting is a combination of a taxane; either paclitaxel or docetaxel and a platinum agent; either cisplatin or carboplatin. Although high initial responses are seen with these primary therapies, most will recur. Salvage chemotherapy thus becomes the mainstay of treatment for many patients with this disease. The goals of salvage therapy are to maximize tumor response while maintaining quality of life with minimal toxicity. As a consequence, there are a number of agents that have been studied in this recurrent setting with significant antitumor activity. Two such novel agents, topotecan and docetaxel are the basis of this phase I, II study.

Patients can be grouped into prognostic categories based on their responses to primary therapy. Those with persistent disease or recurrence within 6 months of treatment are deemed platinum resistant and those achieving a greater than 6 month progression free interval are deemed platinum sensitive. This distinction is important because those that are platinum sensitive have an improved overall survival and higher response rates to salvage chemotherapy. The magnitude of this response increases with an increasing progression free interval. The response of these patients to reintroducing either platinum or paclitaxel has been established. Thigpen et. al. showed a 44% overall response rate(ORR) to paclitaxel infused over 24 hours in 16 patients with a platinum free interval of greater than or equal to 6 months. Kavanagh et. al. demonstrated a 21% partial response rate (PR) to the reintroduction of carboplatin after taxane treatment in 26 patients with a 12-month platinum-free intraval following platinum-refractory ovarian cancer.

Topotecan has been shown to have similar activity as paclitaxel as a second line therapy with non-cross resistance. Topotecan is usually administered in a daily infusion over 30 minutes in doses of 1.5 mg/m2/d x 5 consecutive days every 21 days. In an effort to decrease toxicity and maintain response rates, weekly schedules of topotecan have been explored. Homesley et. al. conducted a phase I trial with single agent weekly topotecan evaluating dosages from 1.5 to 6 mg/m2/wk. The recommended phase II dosage for weekly topotecan was determined to be 4 mg/m2/wk. Dose limiting toxicities consisted of 70 non-hematologic events in 32 of 35 evaluable patients, primarily consisting of grade 1 or 2 chronic fatigue (16%) and gastrointestinal (nausea and vomiting \[23%\]) with the majority (80%) being grade 1 in severity. Dose limiting myelotoxicity and thrombocytopenia were not an issue at the weekly dosages evaluated in this trial. Morris and colleagues at Wayne State University are currently studying weekly topotecan in platinum sensitive patients and have reported a 40% partial response rate with 35% having stable disease. Myelotoxicity was infrequent and included grade 3 or 4 neutropenia in 1.1% and grade 3 anemia in 1.8%. Nonhematologic toxicity included grade 3 fatigue in 17% of patients.

Abu-Rustum et. al. conducted a phase I trial of weekly paclitaxel (60 -100 mg/m2 over 1-hour) in platinum resistant patients (n = 18 patients, recommended phase II dose 80 mg/mg/wk). Dose limiting toxicity was defined as two or more patients with treatment delay or grade 3 toxicity at the same dose level. Treatment was delayed in 2 of 3 patients at the 100 mg/m2 dose level due to ANC \< 1500. In addition they reviewed Memorial Sloan Kettering's previous data with weekly paclitaxel (60 to 100 mg/m2/wk) in platinum resistant patients and found an overall response rate (either documented tumor shrinkage or decrease in serum CA-125 levels) of 28% (ORR in 13 of 45 patients). In a follow up phase II trial, Markman et. al. reported a 25% objective response rate in 13 of 51 platinum resistant patients (4 by decreasing CA-125 and 9 by 50% reduction in tumor volume). Only 1% (13 of 887 dosages) required a dose modification due to toxicity with weekly paclitaxel at 80 mg/m2/wk. Weekly paclitaxel is an active second-line regimen and is generally well tolerated.

In advanced, platinum-refractory ovarian cancer, docetaxel administered every 3 weeks has demonstrated substantial single-agent efficacy with response rates ranging from 24% to 40% and an overall survival of 8 to 10.4 months. Neutropenia was the predominant Grade 3 /4 toxicity, followed by fluid retention, hypersensitivity reactions and diarrhea.

The combination of docetaxel and carboplatin has been studied as first-line therapy for the treatment of epithelial ovarian cancer. A phase II study by Markman et.al. utilized docetaxel 60 mg/m2 plus carboplatin AUC 6 every 3 weeks demonstrated an overall response rate of 81%. The most common hematologic toxicity was Grade 4 neutropenia (64%), while neutropenic fever was observed in only 6% of those patients. The most common non-hematologic toxicity was a mild hypersensitivity reaction (34%) that did not prevent patients from completing their planned therapy.

Preliminary results have recently been reported from a randomized phase III trial comparing docetaxel (75 mg/m2/1 hr infusion) to paclitaxel (175 mg/m2/3 hr infusion) in combination with carboplatin (AUC 5 as calculated by 51Cr-EDTA secretion) every 3 weeks as first-line chemotherapy following surgery for Stage Ic-IV ovarian cancer. Both combinations demonstrated very high overall response rates of 65% and 62%, respectively, and an estimated 1 year disease free survival is approximately 60% for both treatment groups. With regard to toxicity, the occurrence of Grade 2-4 sensory neurotoxicity was significantly increased in patients receiving paclitaxel (30%) compared to docetaxel (11%; p\<.001) and accounted for the majority of toxicity related treatment withdrawal in the paclitaxel group. The most common severe side effect was myelosuppression with Grade 3 or 4 neutropenia occurring in 84% of patients treated with paclitaxel and 94% of patients treated with docetaxel (p\<.001). Febrile neutropenia was noted in 10% of patients treated with docetaxel, compared to 2% of patients treated with paclitaxel (p\<.001). However, there was no difference in septic mortality between the two treatment arms.

In order to decrease the incidence of hematological toxicity associated with docetaxel administered every three weeks, clinicians have explored the use of docetaxel on a weekly schedule. There have been numerous published reports examining the role of weekly docetaxel (single agent and in combination chemotherapy regimens) in wide range of solid tumors including breast, NSCLC, prostate and ovarian. Weekly administration of docetaxel resulted in substantial clinical activity, was well tolerated and resulted in a decreased incidence of hematologic toxicity (grade 3/4 neutropenia and leukopenia each reported in ≤16% of patients; grade 3/4 anemia and thrombocytopenia in ≤13% and ≤3% of patients, respectively. Acute toxicities were uncommon, as was peripheral neuropathy. Prolonged treatment with weekly docetaxel results in chronic toxicities, including asthenia (fatigue), edema, tearing (excessive lacrimation or epiphora), and nail changes. Chronic toxicities have been most prominent when docetaxel has been administered on a continuous weekly basis, i.e., without a break. Toxicities appeared to be delayed in onset or avoided by providing treatment breaks. The current strategy is treating weekly 2 out of 3 weeks on an every 21-day cycle or weekly 3 out of 4 weeks on an every 28-day cycle. The reduced incidence of myelosuppression may enhance the feasibility and tolerability of weekly docetaxel-containing combination regimens.

Burris and colleagues have enrolled 36 patients in a phase I study of weekly docetaxel (20, 25, 30 mg/m2/wk) and weekly topotecan (2.0, 3.0, 3.5 to 4 mg/m2/wk) for solid tumors. The combination of weekly docetaxel 30 mg/m2/wk plus topotecan 3 mg/m2/wk on days 1, 8 and 15 every 28 days resulted in no dose-limiting toxicities and no dose reductions or treatment omissions were warranted during cycle 1 of therapy. Non-hematologic toxicities consisted of grade 1 and 2 nausea, vomiting, fatigue and weakness. Dose-limiting toxicity was documented for weekly docetaxel 30 mg/m2/wk plus topotecan 4 mg/m2/wk with two patients experiencing day 15 dose omissions (one patients with platelets 53 K and ANC 500 and one patient with platelets 27 K who was previously treated with oxaliplatin. Eleven patients have been treated to date with weekly docetaxel 30 mg/m2/wk plus topotecan 3.5 mg/m2/wk. Two patients were non-evaluable, one due to rapidly progressive disease and one due to noncompliance. Of the nine evaluable patients, five patients experienced dose-limiting toxicities as follows, (1) cycle 1 day 15 (C1D15) held due to platelets 33K in a heavily pretreated patient, including previous oxaliplatin, (2) C1D15 dose decreased due to grade 3 diarrhea, (3) C1D8 held due to grade 3-4 nausea and vomiting (may have been disease related), (4) C1D15 held due to platelets 49 K (74 yo, heavily pretreated including previous XRT), (5) C1D15 held due to platelets 43K and declining creatinine clearance of 43 ml/min (3 prior regimens, including XRT, PS 2 and history of thrombocytopenia). One additional patient is planned to complete this dose level, to provide 10 evaluable patients. Of the 36 patients receiving 76 cycles of therapy, myelosuppression was brief and reversible with no febrile neutropenia. Per verbal communication from Dr. Burris, the recommended phase II dose will be docetaxel 30 mg/m2/wk plus topotecan 3.5 mg/m2/wk on days 1, 8 and 15 every 28 days for minimally pretreated patients.

Given the results of these data and the goal to increase response rates in platinum resistant recurrent EOC patients it would seem prudent to evaluate the safety and efficacy of weekly docetaxel 30 mg/m2/wk plus weekly topotecan 3.5 mg/m2/wk via a phase II trial. Results of this trial will be important by expanding our current knowledge base utilizing weekly scheduling of chemotherapeutic agents in regard to toxicities and response rates in platinum resistant EOC.

Platinum-Resistant, Recurrent Epithelial Ovarian Cancer

A Phase II Study of Weekly Docetaxel and Topotecan in Patients With Platinum-Resistant, Recurrent Epithelial Ovarian Cancer

GlaxoSmithKline

Carilion Clinic

Urinary Bladder Neoplasms

Non-Muscle Invasive Bladder Neoplasms

Urologic Neoplasms

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Pharmaceutical Solutions

Cohort I: 2% cis-UCA solution (50 ml); min 3, max 12 patients

cis-UCA solution

Cohort II: 4% cis-UCA solution (50 ml); min 0, max 12 patients

Cohort III: 6% cis-UCA solution (50 ml); min 0, max 12 patients

Juha Peltonen, MD

Liisa Pylkkänen, MD, PhD

The purpose of this study is to evaluate safety, tolerability and pharmacokinetics of intravesical cis-urocanic acid in patients with primary or recurrent non-muscle invasive bladder cancer.

This is a single dose, dose-escalating, Phase I study to evaluate safety, tolerability and pharmacokinetics of intravesical cis-urocanic acid (cis-UCA) in patients with primary or recurrent non-muscle invasive bladder cancer.

The primary objectives is to evaluate safety and tolerability of cis-UCA after a single intravesical instillation with escalating doses and to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of cis-UCA after a single intravesical instillation with escalating doses.

The secondary objectives are to evaluate pharmacokinetics of cis-UCA after a single intravesical instillation with escalating doses, to obtain preliminary information on possible anti-tumor effects of cis-UCA by cystoscopy and histological evaluation after a single intravesical instillation with escalating doses, and to evaluate the effects of cis-UCA on different surrogate biochemical markers on tumor growth and differentiation after a single intravesical instillation with escalating doses.

The key eligibility criteria are the following: Patients with primary or recurrent non-muscle invasive bladder cancer; eligible for intravesical treatment; age 18-80 years; WHO performance status 0-2; acceptable liver, renal and hematological function within 30 days prior to inclusion.

At minimum 3 patients and at maximum 24 patients is planned to be included in the study. The fixed dose-escalation levels will be used.

Up to three dose cohorts are planned to be included:

* Cohort I: 2% cis-UCA solution (50 ml); min 3, max 12 patients
* Cohort II: 4% cis-UCA solution (50 ml); min 0, max 12 patients
* Cohort III: 6% cis-UCA solution (50 ml); min 0, max 12 patients

Cis-urocanic Acid (Cis-UCA) in Patients With Primary or Recurrent Non-muscle Invasive Bladder Cancer

A Single Dose, Dose-escalating, Phase I Study to Evaluate Safety, Tolerability and Pharmacokinetics of Intravesical Cis-urocanic Acid (Cis-UCA) in Patients With Primary or Recurrent Non-muscle Invasive Bladder Cancer

Change in tumor size from baseline by cystoscopy, change in tumor proliferation marker Ki-67 by immunohistochemistry, change in caspase-3 expression by immunohistochemistry

Turku University Hospital

Tampere University Hospital

FinnMedi Oy

BioCis Pharma Ltd

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Dedicated ultrasonographic probe during bronchoscopy

François TRANQUART, PR

The exploration of neoplastic pulmonary pathology is based on computed tomography and bronchoscopy. This allows targeted samples of the identified lesions.

A new ultrasonographic method is proposed as a non invasive and non irradiating technic by using a dedicated probe easily introduced via the channel of the fibrescope, so as to complete the identification of peripheral lesions.

The main objective of the study is to assess the ability of endobronchial ultrasonography to diagnose peripheral pulmonary lesions during the bronchoscopy and to correlate the abnormalities to computed tomography and/or histology.

The dedicated probe consist of a linear array of 2-3 mm in diameter connected to a commercial unit.

Bronchial Ultrasonography Via a Fibrescope: Pilot Study in Tumoral Disease

University Hospital, Tours

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Anti-Infective Agents

Trastuzumab

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Immunosuppressive Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Tubulin Modulators

Antimitotic Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antineoplastic Agents, Immunological

docetaxel

cyclophosphamide

trastuzumab

liposomal doxorubicin

Andrea De Matteis, M.D.

Giuseppe D'Aiuto, M.D.

Francesco Perrone, M.D., Ph.D.

The purpose of this study is to evaluate the rate of pathologic complete response when giving docetaxel and trastuzumab followed by caelyx (liposomal doxorubicin), cyclophosphamide and trastuzumab before surgery in treating women with operable or locally advanced HER-2 positive breast cancer.

Chemotherapy in association with trastuzumab, a monoclonal antibody, given before surgery, has been shown to reduce tumor size and permit better resection of HER-2 positive breast cancers. This study will evaluate the activity of a neoadjuvant treatment with docetaxel and trastuzumab given every 3 weeks for 4 cycles, followed by the combination of caelyx, cyclophosphamide and trastuzumab every 3 weeks for 4 cycles. Patients will undergo breast cancer surgery 2-5 weeks after the completion of neoadjuvant therapy. Adjuvant therapy after surgery will be given according to existing guidelines, and will include an additional 10 cycles of trastuzumab.

CETRA: Neoadjuvant Caelyx and Trastuzumab in Her-2 Positive Breast Cancer

Neoadjuvant Therapy With Trastuzumab and Docetaxel Followed by Trastuzumab, Caelyx (Liposomal Doxorubicin) and Cyclophosphamide in Operable or Locally Advanced Her-2 Positive Breast Cancer

National Cancer Institute, Naples

Immunologic Deficiency Syndromes

IgA Deficiency

Blood Protein Disorders

Hematologic Diseases

Syndrome

Immunoglobulin A

B-Lymphocyte Stimulator (BLyS)

This study will examine the safety of BlyS, an experimental drug being developed to treat immune deficiency. As of July 17, 2001, 7 persons with common variable immune deficiency (CVID) have received BlyS, with no problems reported. This study will test the safety of the drug in people with IgA deficiency.

Patients 18 years of age and older with IgA deficiency who have recurrent or chronic sinus or lung infections or chronic diarrhea or malabsorption may be eligible for this study. Candidates will be screened with a physical examination, blood and urine tests, electrocardiogram (EKG), chest X-ray and a breathing test (spirometry).

Participants will be divided into five groups of three persons each to receive different doses (0.1, 1, 5, 15 or 45 micrograms/kilogram of body weight) of BlyS. The first group will receive a single dose at the lowest dose level (0.l mg). Each succeeding group will receive a single higher dose following a 2-week observation period of the preceding group. The drug will be injected under the skin, with vital signs (temperature, pulse, blood pressure and breathing rate) monitored for one hour after dosing. Blood samples will be collected several times on the day of dosing (before the dose and at 1.5, 3, 5, 8 and 12 hours after the dose) and again at 1,2, 4, 8 and 12 weeks after the dose to measure BlyS levels and evaluate safety. Participants receiving one of the three higher doses will have additional blood samples collected 36, 48 and 60 hours after the dose. Blood will also be collected from all participants 6 and 12 months after dosing to look for any unexpected long-term effects. A total of 289 ml (1.2 cups) of blood will be collected.

Blood will be checked for changes in blood count, kidney and liver function, antibody levels and autoimmune problems. Saliva will be collected four times by placing a cotton ball in the mouth-once before the dose and three times after the dose-to measure antibody levels.

Urine samples will also be collected during the study.

B Lymphocyte Stimulator (BLyS (Trademark)) is a member of the tumor necrosis factor (TNF) superfamily of cytokines that is expressed on peripheral blood monocytes and dendritic cells. Cellular receptors for BLyS are detected on mature immunoglobulin (Ig) expressing B-lymphocytes. In vitro studies show that BLyS increases B cell number, Ig production, antigen-specific immunoglobulin response, and induces production of secretory IgA.

B-cells collected from patients with Common Variable Immune Deficiency show evidence for BLyS binding to B cells and enhanced immunoglobulin secretion.

In 28-day toxicology studies in mice, pharmacological effects were restricted to B lymphoid tissues including B lymphocyte hyperplasia, increased splenic weight without significant increase in spleen size, and increased immunoglobulin production. Murine models suggest that all of the pharmacological effects are fully and rapidly reversible.

The biological profile of BLyS suggests that it may have therapeutic utility in the treatment of immunodeficiency disorders characterized by low or absent immunoglobulin such as selective IgA deficiency (IGA-D).

Risk that BLyS might contribute to IGA-D complications has been assessed. A series of special in vitro and short-term in vivo studies have shown BLyS does not enhance tumorigenicity or allergy/hypersensitivity. Enhanced autoimmunity with immune complex formation could not be ruled out in two mouse studies in which BLyS was administered at higher doses on multiple dosing schedules. Renal changes with glomerular protein deposits were noted in a subset of mice treated at 0.1 and 1.0 mg/kg in the first study and 0.3 and 3.0 mg/kg in the second study. Renal changes have not been reproducible in either of 2 repeat mouse studies designed to replicate conditions on the first study. Renal changes were not observed in the GLP toxicity study in which mice were treated for 4 weeks with BLyS followed by a 2-week recovery period, or in an exploratory monkey study.

This study is a phase I; single-dose, open-label, non-randomized, dose escalation study of BLyS administered subcutaneously to a total of 20 evaluable subjects with IgA-D. Each subject will receive a single dose of BLyS.

The proposed study consists of a screening phase, a 1-day treatment phase with pharmacokinetic sampling, day 2 and day 3 follow-up, and 1, 2, 4, 8, and 12-week acute safety evaluations. Dose escalation to the next cohort is dependent on results of the 2-week acute safety evaluation. Autoimmunity and interim infection history will be evaluated 4-6 weeks and 6 and 12 months. Long-term data will be collected on incidence of malignancy for a minimum of one year.

B-Lymphocyte Stimulator (BLyS) To Treat Selective IgA Deficiency

A Phase I Dose Escalation Study of B-Lymphocyte Stimulator (BLyS) Administered Subcutaneously in Patients With Selective IgA Deficiency

National Cancer Institute (NCI)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
LOC-R01 Study of Lenalidomide and Ibrutinib in Association With Rituximab-Methotrexate Procarbazine Vincristin (R-MPV)	NCT04446962	Lymphoma, Large... Central Nervous...	Lenalidomide Ibrutinib	18 Years - 65 Years	Institut Curie
Platinum-Resistant, Recurrent Epithelial Ovarian Cancer	NCT00484666	Ovarian Cancer		18 Years -	Carilion Clinic
Cis-urocanic Acid (Cis-UCA) in Patients With Primary or Recurrent Non-muscle Invasive Bladder Cancer	NCT01458847	Non-muscle Inva...	cis-UCA solutio... cis-UCA solutio... cis-UCA solutio...	18 Years - 80 Years	BioCis Pharma Ltd
Bronchial Ultrasonography Via a Fibrescope: Pilot Study in Tumoral Disease	NCT00241267	Pulmonary Neopl...	Dedicated ultra...	18 Years -	University Hospital, Tours
CETRA: Neoadjuvant Caelyx and Trastuzumab in Her-2 Positive Breast Cancer	NCT00434031	Breast Cancer	docetaxel cyclophosphamid... trastuzumab liposomal doxor...	18 Years - 65 Years	National Cancer Institute, Naples
B-Lymphocyte Stimulator (BLyS) To Treat Selective IgA Deficiency	NCT00024934	IgA Deficiency	B-Lymphocyte St...	-	National Institutes of Health Clinical Center (CC)
Biological and Clinical Effects of Palbociclib With Ovarian Suppression and Letrozole in the Neoadjuvant Treatment of Breast Cancer	NCT03628066	Breast Cancer	Letrozole Palbociclib Goserelin Oncotype DX Bre...	18 Years -	NSABP Foundation Inc
Primary Chemotherapy With Adriamycin/Cyclophosphamide(AC) vs Taxotere/Xeloda(TX) for Stage II and III Breast Cancer	NCT00352378	Breast Cancer	Anthracycline, ...	18 Years -	National Cancer Center, Korea
Bronchial Ultrasonography Via a Fibrescope: Pilot Study in Tumoral Disease	NCT00241267	Pulmonary Neopl...	Dedicated ultra...	18 Years -	University Hospital, Tours
CRLX101 in Combination With Bevacizumab for Recurrent Ovarian/Tubal/Peritoneal Cancer	NCT01652079	Ovarian Cancer Fallopian Tube ... Primary Periton...	CRLX101	18 Years -	Massachusetts General Hospital
ANET Electrosurgery Applicator Pilot Evaluation Study	NCT03400748	Lung Cancer Lung Cancer Met...	RF Ablation	18 Years -	Olympus Corporation of the Americas
Bronchial Ultrasonography Via a Fibrescope: Pilot Study in Tumoral Disease	NCT00241267	Pulmonary Neopl...	Dedicated ultra...	18 Years -	University Hospital, Tours

Spots Global Cancer Trial Database for primary

Every month we try and update this database with for primary 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 primary

Every month we try and update this database with for primary 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 primary 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.