Safety and Efficacy Study of Iodine-131 Anti-B1 Antibody Plus CHOP For Untreated Mantle Cell Lymphoma

November 19, 2019 updated by: GlaxoSmithKline

Phase II Study Of Iodine-131 Anti-B1 Antibody Plus CHOP For Patients With Previously Untreated Mantle Cell Lymphoma

The primary efficacy endpoint of this study is to determine the duration of response of the sequential administration of Iodine-131 Anti-B1 Antibody followed by six cycles of CHOP for patients with previously untreated Mantle Cell Lymphoma (MCL). The secondary efficacy endpoints for this study are to determine the response rate, confirmed response rate, complete response rate, confirmed complete response rate, duration of response for confirmed responders, duration of response for complete responders, duration of response for confirmed complete responders, progression-free survival, time to treatment failure, and the predictive value of detection of minimal residual disease by molecular techniques on response duration. The pharmacokinetic endpoint is to determine the total body residence time of Iodine-131 Anti-B1 Antibody following the dosimetric dose. The safety endpoints are to determine the incidence of adverse experiences, hematologic toxicity, (e.g., nadir, time to nadir, and time to recovery), use of supportive care, percent of patients converting to human anti-murine antibody (HAMA) positivity, the effects of Iodine-131 Anti-B1 Antibody on the growth and function of hematopoietic progenitor cells, and survival of patients with previously untreated MCL treated with Iodine-131 Anti-B1 Antibody followed by six cycles of CHOP.

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.
25

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 2

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients must have a confirmed initial diagnosis of mantle cell non-Hodgkin's lymphoma by histology according to the WHO classification .
  • Patients must have Ann Arbor bulky stage II, stage III, or stage IV disease at diagnosis. Bulky stage II disease is defined as a mediastinal mass greater than one-third of the maximum chest diameter, or any other mass greater than or equal to 10 cm in maximum diameter.
  • Patients must have less than an average of 25% of the intratrabecular marrow space involved by NHL in bilateral bone marrow biopsy specimens as assessed microscopically at study entry. A unilateral bone marrow biopsy demonstrating <10% involvement with NHL is also adequate.
  • Patients must have evidence that their tumor tissue expresses the CD20 antigen. Immunoperoxidase stains of paraffin-embedded tissue showing positive reactivity with L26 antibody or immunoperoxidase stains of frozen tissue showing positive reactivity with Anti-B1 Antibody (Coulter Clone) or similar commercially available CD20 antibody or evidence of CD20 positivity by flow cytometry are acceptable evidence of CD20 positivity. This must be performed within 42 days of study entry.
  • Patients must have a performance status of at least 60% on the Karnofsky Performance Scale and an anticipated survival of at least 3 months.
  • Patients must have an ANC greater than or equal to 1500 cells/mm3 and a platelet count greater than or equal to 100,000 cells/mm3 within 14 days of study enrollment. These blood counts must be sustained without support of hematopoietic cytokines or transfusion of blood products.
  • Patients must have adequate renal function (defined as serum creatinine <1.5 times the upper limit of normal) and hepatic function (defined as total bilirubin <1.5 times the upper limit of normal and AST <5 times the upper limit of normal) within 14 days of study enrollment.
  • Patients must have bi-dimensionally measurable disease. At least one lesion must be greater than or equal to 2.0 x 2.0 cm by computerized tomography scan.
  • Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment.
  • Patients must have a cardiac left ventricular ejection fraction of greater than or equal to 50% by ventriculography or echocardiogram.

Exclusion Criteria:

  • Patients who have received prior chemotherapy, biologic therapy, steroids, or radiation therapy as treatment for their MCL
  • Patients with active obstructive hydronephrosis
  • Patients with serious illness that would preclude evaluation
  • Patients with prior malignancy other than lymphoma, except for adequately treated skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for 5 years
  • Patients with known HIV infection
  • Patients who are HAMA positive
  • Patients with known brain or leptomeningeal metastases.
  • Patients who are pregnant or breastfeeding. Males and females must agree to use a contraceptive method while on study and for 6 months after receiving Iodine-131 Anti-B1 Antibody.
  • Patients with active infection requiring IV anti-infectives at the time of study enrollment.

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: Tositumomab and Iodine I 131 Tositumomab followed by CHOP
Biological: Tositumomab and Iodine I 131 Tositumomab followed by CHOP
Patients will receive an infusion of unlabeled Tositumomab (450 mg) followed by an infusion of Tositumomab (35 mg) containing 5 mCi of Iodine-131 (dosimetric dose). Whole body gamma camera scans will be obtained on Day 0; Day 2, 3, or 4; and Day 6 or 7 following the dosimetric dose. Patients will then receive an infusion of unlabeled Tositumomab (450 mg) followed by an infusion of 35 mg Tositumomab containing a patient-specific dose of Iodine-131 calculated to deliver a 75 cGy total body radiation dose (therapeutic dose). Patients who have platelet counts of 100,000-149,000 cells/mm3 will receive 65 cGy; obese patients will be dosed based upon 137% of their lean body mass. Patients will be treated with a thyroid blocking agent 24 hours prior to the dosimetric dose and continuing for 14 days following the therapeutic dose. Approximately 13 weeks following the therapeutic dose, CHOP will be administered every 21 days for a total of 6 cycles.

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 the Indicated Unconfirmed Response (Complete Response, Complete Response Unconfirmed, and Partial Response)
Time Frame: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
Participants with response include those with complete response (CR: complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms), complete response unconfirmed (CRu: CR, with one of the following: residual lymph node mass >1.5 centimeters [cm] that has regressed by more than 75% in the sum of the product of the diameters or indeterminate bone marrow), or partial response (PR: >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions).
Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

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 the Indicated Confirmed Response (Confirmed Complete Response, Complete Response Unconfirmed, and Partial Response)
Time Frame: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
A confirmed response is defined as a response that was confirmed by two separate response evaluations occurring at least 4 weeks apart. Participants with a confirmed response include those with complete response (CR: complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms), complete response unconfirmed (CRu: CR, with one of the following: residual lymph node mass >1.5 cm that has regressed by more than 75% in the sum of the product of the diameters or indeterminate bone marrow), or partial response (PR: >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions). The individual rows for confirmed CR, confirmed CRu, and confirmed PR represent confirmation of the same response. For example, a confirmed CR indicates that a CR was followed by another CR at least 4 weeks later.
Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
Duration of Response for All Confirmed Responders (CR + CRu + PR)
Time Frame: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
Complete response (CR) is defined as the complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms. Complete response unconfirmed (CRu) is defined as CR, with one of the following: residual lymph node mass >1.5 cm that has regressed by more than 75% in the sum of the product of the diameters or indeterminate bone marrow. Partial response (PR) is defined as a >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions. For participants with CR, CRu, or PR, duration of response is defined as the time from the first documented response to the first documented progression.
Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
Duration of Response for All Unconfirmed Responders (CR + CRu + PR)
Time Frame: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
Complete response (CR) is defined as the complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms. Complete response unconfirmed is defined as CR, with one of the following: residual lymph node mass >1.5 cm that has regressed by more than 75% in the sum of the product of the diameters or indeterminate bone marrow. Partial response (PR) is defind as a >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions. Duration of response is defined as the time from the first documented response to the first documented progression.
Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
Duration of Response for Unconfirmed Complete Responders
Time Frame: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
Complete response is defined as the complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms. Duration of response is defined as the time from the first documented response to the first documented progression.
Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
Duration of Response for Confirmed Complete Responders
Time Frame: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
Complete response is the complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms. A confirmed response is defined as a response that was confirmed by two separate response evaluations occurring at least 4 weeks apart. Duration of response is defined as the time from the first documented response to the first documented progression.
Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
Progression-free Survival
Time Frame: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
Progression-free survival is defined as the time from the start of treatment (i.e., the dosimetric dose) to the first documented disease progression or death. Disease progression is defined as a >=25% increase from the nadir value of the sum of the products of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must have been greater than 2 centimeters (cm) in diameter by radiographic evaluation or greater than 1 cm in diameter by physical examination.
Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
Time to Treatment Failure
Time Frame: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
Time to treatment failure is defined as the time from the date of the dosimetric dose to the first occurrence of treatment withdrawal, decision to seek additional therapy, study removal, disease progression, alternative therapy, or death.
Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
Time Frame: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAEs are defined as those events that were fatal or immediately life-threatening, and those events that resulted in hospitalization; prolonged an existing hospitalization; resulted in disability; or was a congenital anomaly. Refer to the general AE/SAE module for a complete list of all AEs and SAEs.
Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
Mean Nadir Value for Absolute Neutrophil Count (ANC)
Time Frame: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
Nadir is defined as the lowest laboratory value recorded following the administration of study medication. ANC is a measure of the number of neutrophil granulocytes present in the blood. Neutrophils are a type of white blood cell that fights infection.
Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
Mean Nadir Value for Hemoglobin
Time Frame: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
Nadir is defined as the lowest laboratory value recorded following the administration of study medication. Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells.
Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
Mean Nadir Values for Platelets and White Blood Cell (WBC) Count
Time Frame: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
Nadir is defined as the lowest laboratory value recorded following the administration of study medication. Platelets and WBCs are types of blood cells.
Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
Time to Nadir for the Indicated Hematology Parameters
Time Frame: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
Hematology parameters include ANC (calculated), hemoglobin, platelet count, and WBC count. Nadir is defined as the lowest laboratory value recorded following the administration of study medication. Time to nadir is defined as the time from Baseline to the time the lowest value recorded following the therapeutic dose.
Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
Time to Recovery From the Indicated Hematology Parameters
Time Frame: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
Hematology parameters include ANC (calculated), hemoglobin, platelet count, and WBC count. Nadir is defined as the lowest laboratory value recorded following the administration of study medication. Time to recovery to Baseline for the indicated hematologic parameters is defined as the time required for recovery from nadir values to Baseline values.
Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
Number of Participants Negative for Human Anti-Murine (Mouse) Antibody (HAMA) at Screening Who Converted to HAMA Positivity or Remained Negative During the Course of the Study
Time Frame: Screening; at Week 7, Week 13, then every 6 months until disease progression or death (up to 143 months)
The number of participants who developed human anti-murine (mouse) anibodies (HAMA) after treatment was measured. Conversion to HAMA positivity is relative to Screening (participants were evaluable for HAMA analysis if they were HAMA negative at Screening).
Screening; at Week 7, Week 13, then every 6 months until disease progression or death (up to 143 months)
Number of Participants With an Adverse Event of Cytopenia
Time Frame: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
The effects of iodine I-131 tositumomab on the growth and function of hematopoietic progenitor cells was measured as the number of participants who had cytopenia. An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
Overall Survival
Time Frame: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)
Overall survival is defined as the time from the start of treatment to the date of death from any cause.
Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

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.
GlaxoSmithKline

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.
June 28, 2001

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.
June 30, 2013

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.
June 30, 2013

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).
October 8, 2009

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.
October 8, 2009

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.
October 9, 2009

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.
December 4, 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.
November 19, 2019

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, 2019

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.
  • 393229/005

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

IPD for this study will be made available via the Clinical Study Data Request site.

IPD Sharing Time Frame

IPD is available via the Clinical Study Data Request site (click on the link provided below)

IPD Sharing Access Criteria

Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

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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