Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

B-cell Lymphoma

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Infective Agents

Inotuzumab Ozogamicin

Rituximab

Antineoplastic Agents, Immunological

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Immunotoxins

Immunoconjugates

1.8 mg/m2, IV on day 2 of each 28 day cycle; up to 8 cycles unless PD, unacceptable toxicity, or subject's refusal occurs.

Inotuzumab Ozogamicin (CMC-544)

375 mg/m2, IV on day 1 of each 28 day cycle; up to 8 cycles unless PD, unacceptable toxicity, or subject's refusal occurs.

Rituximab (Rituxan)

Pfizer CT.gov Call Center

To assess the tolerability and the initial safety profile of Inotuzumab Ozogamicin (CMC-544) in combination with Rituximab in patients with B-Cell Non-Hodgkin's lymphoma (NHL).

Study Evaluating The Safety And Tolerability Of Combination Therapy Inotuzumab Ozogamicin (CMC-544) And Rituximab

A Phase 1 Study Of Cmc-544 Administered In Combination With Rituximab In Subjects With B-cell Non-hodgkin's Lymphoma

CMC-544 is composed of G544, an anti-human CD22 antibody, linked to a potent cytotoxic antitumor antibiotic called calicheamicin. CD22 is expressed on the malignant cells of the majority of B-lymphocyte malignancies.

The time measured for the serum concentration to decrease by one half.

AUClast= Area under the serum concentration versus time curve from time zero (pre-dose) to time of last measured concentration.

AUC∞ = Area under the serum concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).

The rate at which a drug is metabolized or eliminated by normal biological processes.

The theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.

A DLT was defined as the following drug-related adverse event which occurred during the first 28 days: 1) Any National Cancer Institute (NCI) Grade 3 or 4 nonhematologic toxicity (except Grade 3 nausea or vomiting without optimal treatment), 2) Febrile neutropenia, 3) Grade 4 absolute neutrophil count lasting \>=7 days, 4) Grade 4 thrombocytopenia lasting \>=3 days, 5) Grade 3 or 4 thrombocytopenia associated with a bleeding episode requiring platelet transfusion, 6)Delayed recovery (to grade \<=1 or baseline, except alopecia) from a drug-related toxicity that delayed the next dose \>2 weeks

Number of participants with objective response of complete response (CR), complete response unconfirmed (CRu), or partial response (PR). Objective response included subjects with CR, CRu, and PR. Response criteria for Non-Hodgkin's Lymphoma (NHL) were based on the 1999 NCI International Workshop to standardize response criteria for NHL. Per the criteria for Lymph node masses: CR, normal size; CRu, normal or \>75% decrease in the sum of the products of the greatest diameters (SPD); PR, normal or \>=50% decrease in the SPD.

The interval from the date of first administration of the test article until the first date on which relapsed disease, progressive disease (PD), or death was documented, censored at the last tumor evaluation date. Response criteria for Non-Hodgkin's Lymphoma (NHL) were based on the 1999 NCI International Workshop to standardize response criteria for NHL. Per the criteria for Lymph node masses: Relapse/PD, appearance of any new lesion or increased by \>=50% in the size.

Pfizer

The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Participants were treated with intravenous rituximab (375 mg/m\^2) followed by intravenous CMC-544 (1.8 mg/m\^2) every 28 days (±2 days) for 4 cycles (1 cycle = 28 days), and participants with at least "stable disease (SD)" after the fourth cycle received CMC-544 up to 8 cycles unless they experienced progressive disease (PD) or an unacceptable toxicity, or withdrew consent.

CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2

Age, Continuous

Sex: Female, Male

Pfizer ClinicalTrials.gov Call Center

Number of Participants With Dose-limiting Toxicities (DLT)

Complete response (CR)

Complete response unconfirmed (CRu)

Partial response (PR)

Objective Response (CR+CRu+PR)

The evaluable population included all participants who received at least 2 doses of the test article and who had a baseline tumor CT scan and underwent at least 1 postbaseline tumor assessment for anticancer clinical activity.

Number of Participants With Objective Response: Evaluable Population

The ITT population included all participants who were enrolled in the intended dose scheme.

Number of Participants With Objective Response: Intent-to-treat (ITT) Population

The evaluable population included all participants who received at least 2 doses of the test article and who had a baseline tumor computed tomography (CT) scan and underwent at least 1 postbaseline tumor assessment for anticancer clinical activity.

Progression-Free Survival (PFS)

CMC-544: Cycle 1

CMC-544: Cycle 2

CMC-544: Cycle 3

Total Calicheamicin: Cycle 1

Total Calicheamicin: Cycle 2

Total Calicheamicin: Cycle 3

G544: Cycle 1

G544: Cycle 2

G544: Cycle 3

Phamacokinetic population included participants who received at least 1 dose of the test article and with serum concentrations available. Number Analyzed = number of participants with the pertinent parameters calculated at the visit.

Maximum Observed Serum Concentration (Cmax) of CMC-544, Total Calicheamicin, and Anti-human CD22 Antibody (G544)

Pharmacokinetic population included participants who received at least 1 dose of the test article and with serum concentrations available. Number Analyzed = number of participants with the pertinent parameters calculated at the visit.

Serum Decay Half-Life (t1/2) of CMC-544, Total Calicheamicin, and G544

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CMC-544, Total Calicheamicin, and G544

Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC∞) of CMC-544, Total Calicheamicin, and G544

Clearance (CL) of CMC-544, Total Calicheamicin, and G544

Volume of Distribution (Vss) of CMC-544, Total Calicheamicin, and G544

Screening

End of Treatment

The intent-to-treat (ITT) population included all participants in the intended dose scheme.

Number of Participants With Positive Serum Antibody to Inotuzumab Ozogamicin (CMC-544)

Number of Participants With Positive Serum Antibody to Rituximab

Overall Study

Nervous System Diseases

Symptoms and General Pathology

Musculoskeletal Diseases

Myasthenia Gravis

Asthenia

Muscle Weakness

Paresis

Muscular Diseases

Neuromuscular Manifestations

Neurologic Manifestations

Syndrome

Paraneoplastic Syndromes

Paraneoplastic Syndromes, Nervous System

Nervous System Neoplasms

Autoimmune Diseases

Autoimmune Diseases of the Nervous System

Neurodegenerative Diseases

Neuromuscular Junction Diseases

Neuromuscular Diseases

Four weekly IV infusions of Rituxan with dosage individually calculated per subject.

Rup Tandan, MD, FRCP

Myasthenia gravis is a disease that happens because the immune system attacks the nervous system. The damage is caused by antibodies produced by B lymphocytes. These antibodies damage a special part of the muscle that helps transmit impulses from nerves to muscles to allow muscles to work properly. This damage results in symptoms of myasthenia gravis. Participants are being asked to participate in this research study because their myasthenia gravis has either failed to respond to treatments commonly used in the disease, or they have had bad side-effects from such treatments.

This is a research study of a drug called Rituximab. Rituximab, also called Rituxan, is a mouse antibody that has been changed to make it similar to a human antibody. Antibodies are proteins that can protect the body from foreign invaders, such as bacteria and viruses, by binding to substances called antigens. Rituxan works by binding to a protein, called the CD20 protein. Rituxan helps to destroy white blood cells that produce antibodies in the body, called B-lymphocytes. It is a treatment given through a vein in the participant's arm over a period of approximately 4-6 hours. It has been approved by the Food and Drug Administration (FDA) for use in patients with a form of cancer of the lymph glands called Non-Hodgkin's Lymphoma (NHL). Rituximab is not approved for their myasthenia gravis.

Treatment with Rituximab is being tried in this research study because Rituximab decreases B lymphocytes. There is preliminary evidence that Rituximab helps some patients with chronic and otherwise difficult to treat myasthenia gravis.

Myasthenia gravis (MG) is an immune-mediated disorder of the neuromuscular junction diagnosed on the basis of clinical, electrophysiological and serological features. Cyclosporine as a disease-modifying therapy has been effective in a controlled study; corticosteroids, immunosuppressive agents such as azathioprine and cyclophosphamide, plasmapheresis and intravenous human immune globulin have shown benefit in uncontrolled trials. There are several drawbacks to currently used medical treatments, including serious and debilitating side-effects, prohibitive costs, and the need for continuous or periodical treatment. Almost 20-25% of patients with MG are unresponsive to commonly used therapies, resulting in significant burden and economic loss. Rituximab is a chimeric anti-CD20 monoclonal antibody which produces a substantial reduction in circulating plasma cells (CD19+) and B cells (CD20+) and provides targeted therapy for B-cell lymphomas. Recently, rituximab has been found to be effective in several antibody-mediated autoimmune processes, including immune thrombocytopenia, autoimmune hemolytic anemia, and IgM-related polyneuropathies. There is preliminary evidence in the literature that treatment of MG patients with rituximab is likely to be of benefit. These observations would strongly suggest that rituximab might benefit refractory MG and needs further study.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study Evaluating The Safety And Tolerability Of Combination Therapy Inotuzumab Ozogamicin (CMC-544) And Rituximab	NCT00724971	Lymphoma, B-Cel...	Inotuzumab Ozog... Rituximab (Ritu...	20 Years - 75 Years	Pfizer
A Pilot Trial of Rituxan in Refractory Myasthenia Gravis	NCT00619671	Refractory Myas...	Rituximab (Ritu...	18 Years - 80 Years	University of Vermont
Study Evaluating The Safety And Tolerability Of Combination Therapy Inotuzumab Ozogamicin (CMC-544) And Rituximab	NCT00724971	Lymphoma, B-Cel...	Inotuzumab Ozog... Rituximab (Ritu...	20 Years - 75 Years	Pfizer

Spots Global Cancer Trial Database for rituximab (rituxan)