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

December 4, 2018 updated by: Pfizer

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

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 Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
      • Aichi, Japan, 466-8650
        • Nagoya Daini Red Cross Hospital
      • Kanagawa, Japan, 259-1193
        • Tokai University Hospital
      • Tokyo, Japan, 104-0045
        • National Cancer Center Hospital
      • Tokyo, Japan, 135-8550
        • Cancer Inst. Hp. of Japanese Foundation for Cancer Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • CD20 and CD22-positive, B-cell NHL which has progressed after 1 or 2 prior therapies.
  • Prior therapy must have contained at least one dose of Rituximab therapy. Patients can not be refractory to Rituximab (refractory = PD under treatment or within 6 month
  • Eastern Cooperative Oncology Group (ECOG) performance status: 0/ 1.
  • Patients must not have received previous radioimmunotherapy.
  • Patients tolerant to Rituximab.
  • Patients must not have received chemotherapy, cancer immunosuppressive therapy, growth factors (except erythropoietin), or investigational agents within 28 days before first dose of test article.

Exclusion Criteria:

  • Candidate for potentially curative therapies
  • Subjects must not have received previous radioimmunotherapy.
  • Subjects with autologous hematopoietic stem cell transplant within the last 6 months

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Inotuzumab Ozogamicin + Rituximab
Drug: Inotuzumab Ozogamicin (CMC-544)
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.
Drug: Rituximab (Rituxan)
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Dose-limiting Toxicities (DLT)
Time Frame: Up to 28 days
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
Up to 28 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Objective Response: Evaluable Population
Time Frame: Up to 8 cycles (1 cycle = 28 days)
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.
Up to 8 cycles (1 cycle = 28 days)
Number of Participants With Objective Response: Intent-to-treat (ITT) Population
Time Frame: Up to 8 cycles (1 cycle = 28 days)
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.
Up to 8 cycles (1 cycle = 28 days)
Progression-Free Survival (PFS)
Time Frame: Up to 591 days
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.
Up to 591 days

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Maximum Observed Serum Concentration (Cmax) of CMC-544, Total Calicheamicin, and Anti-human CD22 Antibody (G544)
Time Frame: Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544
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.
Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544
Serum Decay Half-Life (t1/2) of CMC-544, Total Calicheamicin, and G544
Time Frame: Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544
The time measured for the serum concentration to decrease by one half.
Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CMC-544, Total Calicheamicin, and G544
Time Frame: Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544
AUClast= Area under the serum concentration versus time curve from time zero (pre-dose) to time of last measured concentration.
Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC∞) of CMC-544, Total Calicheamicin, and G544
Time Frame: Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544
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 - ∞).
Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544
Clearance (CL) of CMC-544, Total Calicheamicin, and G544
Time Frame: Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544
The rate at which a drug is metabolized or eliminated by normal biological processes.
Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544
Volume of Distribution (Vss) of CMC-544, Total Calicheamicin, and G544
Time Frame: Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544
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.
Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544
Number of Participants With Positive Serum Antibody to Inotuzumab Ozogamicin (CMC-544)
Time Frame: Up to 8 Cycles (1 cycle = 28 days)
Antibody responses to CMC-544
Up to 8 Cycles (1 cycle = 28 days)
Number of Participants With Positive Serum Antibody to Rituximab
Time Frame: Up to 8 Cycles (1 cycle = 28 days)
Antibody responses to rituximab
Up to 8 Cycles (1 cycle = 28 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 4, 2008

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 10, 2010

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 10, 2010

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 25, 2008

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 29, 2008

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 30, 2008

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 15, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 4, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 3129K3-1104
  • B1931005 (Other Identifier: Alias Study Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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