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

Purpose

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.

Condition	Intervention	Phase
Lymphoma, Mantle-Cell	Biological: Tositumomab and Iodine I 131 Tositumomab followed by CHOP	Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase II Study Of Iodine-131 Anti-B1 Antibody Plus CHOP For Patients With Previously Untreated Mantle Cell Lymphoma

Resource links provided by NLM:

MedlinePlus related topics: Lymphoma

Drug Information available for: Iodine Sodium iodide I 131 Iodide Tositumomab

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

To determine the response rate of sequential administration of Iodine I 131 Tositumomab followed by six cycles of CHOP chemotherapy for patients with previously untreated MCL. [ Time Frame: Patients will be evaluate under long-term follow-up every six months until death. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To assess the efficacy by molecular techniques on response duration, pharmacokinetics, and safety of the sequential administration of iodine I 131 tositumomab followed by six cycles of CHOP for patients with previously untreated MCL. [ Time Frame: Patients will be evaluate under long-term follow-up every six months until death. ] [ Designated as safety issue: Yes ]

Enrollment:	25
Study Start Date:	June 2001
Estimated Study Completion Date:	December 2014
Estimated Primary Completion Date:	December 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: open-label, single arm	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.

Arms

Assigned Interventions

Experimental: open-label, single arm

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00992992

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

No publications provided

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00992992 History of Changes
Other Study ID Numbers:	393229/005
Study First Received:	October 8, 2009
Last Updated:	March 29, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:

Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP)
Tositumomab
Tositumomab and Iodine I-131 tostumomab
Bexxar

Iodine-131 Anti-B1 Antibody
Mantle Cell
radioimmunotherapy

Additional relevant MeSH terms:

Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Antibodies
Antibodies, Monoclonal
Iodine

Cadexomer iodine
Iodine-131 anti-B1 antibody
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Infective Agents, Local
Anti-Infective Agents
Therapeutic Uses
Trace Elements
Micronutrients
Growth Substances
Antineoplastic Agents

ClinicalTrials.gov processed this record on May 16, 2013