Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

All Drugs and Chemicals

Antibodies

Antibodies, Monoclonal

Immunoglobulins

MABp1 administered IV every two weeks, plus best supportive care

Placebo administered IV every two weeks, plus best supportive care

Xilonix is a True Human Monoclonal Antibody targeting Interleukin 1 alpha, and is administered intravenously every 2 weeks with best supportive care until clinical or radiographic progression.

Xilonix

Placebo plus best supportive care will be administered intravenously every 2 weeks until clinical or radiographic progression.

Placebo

Janssen Research & Development, LLC Clinical Trial

The purpose of this study is to determine if the True Human Monoclonal antibody Xilonix (MABp1) can prolong the life of colorectal carcinoma patients that are refractory to standard therapy.

In the setting of refractory, metastatic disease a complete resolution of tumor burden is not a reasonable expectation. Instead, the primary goal of anti-tumor therapy at this stage is to eliminate or reduce the symptomatic effects of the tumor, while trying to prolong survival for as long as possible. Due to treatment related morbidity however, few treatment modalities are ideal for this objective. Even with the most recent targeted agents (such as multi-kinase inhibitors), drug related toxicities frequently lead to relatively short treatment durations. With discontinuation of therapy, disease progression is uncontrolled and prognosis is poor.

New agents that control disease progression-while improving tumor-related symptoms, rather than causing significant therapy related morbidity-are vitally needed to treat patients with advanced cancer, including those with colorectal cancer. An approach has been taken to develop such an agent using a monoclonal antibody to block the chronic inflammation involved in both malignant disease progression and constitutional symptoms.

Xilonix™ is expected to inhibit tumor growth and metastasis by interrupting crucial signals that drive angiogenesis and invasiveness. The antibody therapy may also block tumor microenvironment infiltration by leukocytes (such as myeloid suppressor cells) that suppress antitumor immunity, enabling better host immune control of the disease. In addition to local effects on the tumor, Xilonix™ is expected to work systemically to correct the metabolic dysregulation, fatigue and anxiety mediated by chronic inflammatory signaling to the central nervous system.

A Phase III Study of Xilonix in Patients With Advanced Colorectal Cancer

Phase III Double-blinded, Placebo Controlled Study of Xilonix™ for Improving Survival in Metastatic Colorectal Cancer

Overall survival time was defined as the duration from the date of randomization until death or last follow-up. OS was summarized by Kaplan-Meier method and compared between the treatment groups using un-adjusted log-rank test.

Change from baseline in LBM as measured by Dexa scans was reported. DEXA is an X-ray imaging modality used to determine the mass of one material in the presence of another material, using the knowledge of their unique X-ray attenuation at different energies.

The EORTC QLQ-C30 questionnaire incorporates nine multi-item scales: 5 functional scales (physical, cognitive, role, emotional, and social); 3 symptom scales (pain, fatigue, and appetite loss) and a Global Health Status/QoL scale. Each item, except Global Health Status, is answered on a four-point scale (1-4): 1-not at all, 2-a little, 3-quite a bit, 4-very much. Response to Global Health Status is measured on a 1 to 7 scale. "1" being very poor and "7" being excellent. Each scale (symptom scale \[pain, fatigue, and appetite loss\] and Global Health Status/Quality of Life \[QoL\] scale) was linearly transformed to be in range from 0-100 where a higher score represents good health status, while lower scores indicate poor health status. As planned, the data for symptom scales (pain, fatigue, appetite loss) and a Global Health Status/QoL scale was evaluated and reported.

Change from baseline in platelet counts up to Week 8 was evaluated.

PFS was defined as time from randomization to tumor progression or death. Progressive Disease defined as increase in tumor burden greater than or equals to (\>=) 25 (%) percent relative to nadir (minimum recorded tumor burden) confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented. Participants surviving without disease progression at end of study were censored. PFS was compared by Kaplan-Meier method using log-rank test.

The percentage of OR was estimated by dividing the total number of confirmed complete response (CR) and partial response (PR) by the total number of participants randomized where CR was complete disappearance of all lesions (whether measurable or not, and no new lesions); confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented and PR was decrease in tumor burden \>= 50 % relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation.

Percentage of participants who achieved disease control was estimated by dividing the total number of confirmed CRs, PRs and stable disease (SD) by the total number of participants randomized where CR was complete disappearance of all lesions (whether measurable or not, and no new lesions); confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented, PR was decrease in tumor burden \>= 50% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation and SD defined as not meeting criteria for CR and PR, in absence of Progressive Disease (increase in tumor burden \>= 25 % relative to nadir (minimum recorded tumor burden) confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented).

Janssen Research & Development, LLC

Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.

Participants received 7.5 milligram per kilogram (mg/kg) Xilonix (MABp1) via intravenous (IV) injection once every 2 weeks until evidence of radiographic or clinical progression along with best supportive care (BSC) (up to 18 months).

Participants received placebo via IV injection once every 2 weeks until evidence of radiographic or clinical progression plus BSC (up to 18 months).

Total

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

Australia

Austria

Belgium

Czech Republic

England

Hungary

Israel

Italy

Netherlands

Poland

Spain

Switzerland

Region of Enrollment

< 65 years

Between 65 and 75 years

> 75 years

Missing

Age (years)

Baseline analysis population included all participants who were randomized and received at least one infusion of study drug.

Product Development Portfolio Leader

The modified intent-to-treat (mITT) population included all participants who were randomized and received at least one infusion of study drug.

Overall Survival (OS)

Participants received 7.5 mg/kg Xilonix (MABp1) via IV injection once every 2 weeks until evidence of radiographic or clinical progression along with BSC (up to 18 months).

The per protocol (PP) population was defined as participants that had baseline and follow up values for both the DEXA assessment and the European Organization for Research and Treatment of Cancer (EORTC) questionnaire.

Change From Baseline in Lean Body Mass (LBM) Measured by Dual-energy X-ray Absorptiometry (DEXA) Scans

Statistical Analysis for Global Health Status/Qol

Global Health Status/Qol

Pain

Fatigue

Appetite Loss

The PP population was defined as participants that had baseline and follow up values for both the DEXA assessment and the EORTC questionnaire.

Change From Baseline in Symptom Scale and Global Health Status/Quality of Life (QoL) Assessed Through the Cancer-specific European Organization for Research and Treatment of Cancer - Quality of Life Questionnaire (EORTC QLQ-C30)

Change From Baseline in Platelet Counts

The intent-to-treat (ITT) population consisted of all randomized participants.

Progression Free Survival (PFS)

The mITT population included all participants who were randomized and received at least one infusion of study drug.

Percentage of Participants With Objective Response (OR)

The participants with baseline and follow up radiographic assessments were included in this analysis.

Percentage of Participants With Disease Control

Overall Study

Blood and Lymph Conditions

Immune System Diseases

Heart and Blood Diseases

Symptoms and General Pathology

Rare Diseases

Lymphoma

Multiple Myeloma

Neoplasms, Plasma Cell

Plasmacytoma

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, Mantle-Cell

Lymphoma, B-Cell, Marginal Zone

Lymphoma, Large B-Cell, Diffuse

Lymphoproliferative Disorders

Paraproteinemias

Lymphoma, B-Cell

Hematologic Diseases

Waldenstrom Macroglobulinemia

Blood Protein Disorders

Immunoproliferative Disorders

Neoplasms by Histologic Type

Lymphatic Diseases

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Hemorrhagic Disorders

Lymphoma, Non-Hodgkin

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Lymphocytic Leukemia

Mantle Cell Lymphoma

B-cell Lymphoma

Marginal Zone Lymphoma

Diffuse Large B-Cell Lymphoma

Primary Central Nervous System Lymphoma

Radiopharmaceuticals

Iopofosine I 131 in Waldenstroms Macroglobulinemia

Iopofosine I 131 in Central Nervous System Lymphoma

Iopofosine I 131 in Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma, and Diffuse Large B-Cell Lymphoma

Iopofosine I 131 single dose

Iopofosine I 131 multiple dose

Iopofosine I 131 fractionated dose

Kate Oliver

Cellectar B site

Cellectar Biosciences

Jarrod Longcor

Part A of this study evaluates iopofosine I 131 (CLR 131) in patients with select B-cell malignancies (multiple myeloma( MM), indolent chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and central nervous system lymphoma (CNSL) who have been previously treated with standard therapy for their underlying malignancy. Part B (CLOVER-WaM) is a pivotal efficacy study evaluating IV administration of iopofosine I 131 in patients with WM that have received at least two prior lines of therapy.

B-cell malignancies represent a diverse collection of diseases and, taken together, make up the majority of hematologic malignancies. B-cell lymphomas represent the largest percentage of these neoplasms, and the relapsed and/or refractory B-cell lymphomas have proven very difficult to treat. Patients that have failed prior therapy, including WM patients, represent a very challenging patient population with significantly reduced life-expectancy.

Iopofosine I 131 is a targeted radiotherapeutic that exploits the selective uptake and retention of Cellectar's proprietary phospholipid ethers (PLEs) by malignant cells. Cellectar Biosciences' novel cancer-targeted small-molecule compound is radiolabeled with the radioisotope iodine-131 (I-131) which has previously been used approved for use in select tumors. Iopofosine I 131 has been evaluated in over 80 xenograft and spontaneous (transgenic) tumor models where it was demonstrated to be effective in eliminating tumors.

Based on the critical unmet medical need for effective agents with novel mechanisms of action in B-cell malignancies, Cellectar Biosciences has chosen to expand this ongoing study to assess iopofosine I 131 in a pivotal expansion cohort in Waldenstrom's Macroglobulinemia patients that have received at least two prior lines of therapy.

Study of Iopofosine I 131 (CLR 131) in Select B-Cell Malignancies (CLOVER-1) and Pivotal Expansion in Waldenstrom Macroglobulinemia

An Open-Label, Multicenter, Phase 2 Study of Iopofosine I 131 (CLR 131) in Patients With Relapsed or Refractory (R/R) Select B-Cell Malignancies (CLOVER-1) and Expansion Cohort in Patients With Waldenstrom Macroglobulinemia (CLOVER-WaM)

Response assessment per International Uniform Response Criteria for Multiple Myeloma; Lugano Criteria for lymphoma; International Workshop on Chronic Lymphocytic Leukemia for CLL; VIth Waldenstrom's Macroglobulinemia Criteria for Response Assessment; or 2005 Response Criteria for CNS Lymphoma

Response assessment per criteria modified from VIth Waldenstrom's Macroglobulinemia Criteria for Response Assessment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase III Study of Xilonix in Patients With Advanced Colorectal Cancer	NCT01767857	Metastatic Colo...	Xilonix Placebo	18 Years -	Janssen Research & Development, LLC
Study of Iopofosine I 131 (CLR 131) in Select B-Cell Malignancies (CLOVER-1) and Pivotal Expansion in Waldenstrom Macroglobulinemia	NCT02952508	Waldenstrom Mac... Multiple Myelom... Chronic Lymphoc... Small Lymphocyt... Lymphoplasmacyt... Marginal Zone L... Mantle Cell Lym... Diffuse Large B... Central Nervous...	Iopofosine I 13... Iopofosine I 13... Iopofosine I 13...	18 Years -	Cellectar Biosciences, Inc.
Study of Iopofosine I 131 (CLR 131) in Select B-Cell Malignancies (CLOVER-1) and Pivotal Expansion in Waldenstrom Macroglobulinemia	NCT02952508	Waldenstrom Mac... Multiple Myelom... Chronic Lymphoc... Small Lymphocyt... Lymphoplasmacyt... Marginal Zone L... Mantle Cell Lym... Diffuse Large B... Central Nervous...	Iopofosine I 13... Iopofosine I 13... Iopofosine I 13...	18 Years -	Cellectar Biosciences, Inc.
A Phase III Study of Xilonix in Patients With Advanced Colorectal Cancer	NCT01767857	Metastatic Colo...	Xilonix Placebo	18 Years -	Janssen Research & Development, LLC

Spots Global Cancer Trial Database for pivotal

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

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