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

NCT00992992 | Completed Phase 2 Results

• 1 other identifier: 393229/005
• Study Type: interventional
• Target: 25
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Lymphoma, Mantle-Cell

Keywords

Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP); Tositumomab; Tositumomab and Iodine I-131 tostumomab; Bexxar; Iodine-131 Anti-B1 Antibody; Mantle Cell; radioimmunotherapy

Outcome Measures

Primary Outcomes (1)

• Number of Participants With the Indicated Unconfirmed Response (Complete Response, Complete Response Unconfirmed, and Partial Response)

  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 Outcomes (16)

• Number of Participants With the Indicated Confirmed Response (Confirmed Complete Response, Complete Response Unconfirmed, and Partial Response)

  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)

  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)

  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

  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

  Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Study Arms (1)

Tositumomab and Iodine I 131 Tositumomab followed by CHOP

EXPERIMENTAL

Tositumomab and Iodine I 131 Tositumomab followed by CHOP

Biological: Tositumomab and Iodine I 131 Tositumomab followed by CHOP

Interventions

Tositumomab and Iodine I 131 Tositumomab followed by CHOP BIOLOGICAL

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.

Tositumomab and Iodine I 131 Tositumomab followed by CHOP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Related Publications (1)

• Zelenetz AD, Popplewell LL, Noy A, Horner TJ, Lin TS, Donnelly G, Sgouros G, Rijo I, Divgi CR. Phase 2 Study of Iodine-131 Tositumomab Plus Chemotherapy in Patients With Previously Untreated Mantle-Cell Lymphoma. Clin Lymphoma Myeloma Leuk. 2020 Nov;20(11):749-756.e1. doi: 10.1016/j.clml.2019.04.010. Epub 2019 Apr 29.

  PMID: 32800518 BACKGROUND

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

tositumomab I-131

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2009
• First Posted: October 9, 2009
• Study Start: June 28, 2001
• Primary Completion: June 30, 2013
• Study Completion: June 30, 2013
• Last Updated: December 4, 2019
• Results First Posted: April 8, 2014

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• 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.