Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Non-Hodgkin

Lymphoma, Follicular

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Follicular Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Anti-Infective Agents

Fludarabine

Fludarabine phosphate

Iodine

Cadexomer iodine

Tositumomab I-131

Patients will first receive an abbreviated course of three cycles of fludarabine (25 mg/m2 for 5 days every 5 weeks). Iodine I 131 tositumomab will be initiated 6 to 8 weeks after completion of fludarabine. Patients will undergo dosimetry studies to determine the appropriate patient-specific activity of iodine I 131 tositumomab required to deliver a fixed dose of 75 cGy. The dose will be attenuated to 65 cGy for patients with platelet counts between 100,000 and 150,000/micoliter.

Tositumomab and Iodine I 131 Tositumomab

GSK Clinical Trials

This is a single-arm, single institution, phase II study of fludarabine monophosphate followed by Iodine I 131 Tositumomab for patients with previously untreated, advanced-stage (stage III or IV) low-grade, transformed low-grade and follicular non-Hodgkin's lymphoma. The primary objective of the study will be to evaluate the safety of this treatment combination and the secondary endpoint will be to evaluate efficacy.

Study of Safety and Efficacy of a Sequential Regimen Consisting of Three Cycles of Fludarabine Followed by Tositumomab and Iodine I 131 Tositumomab

Fludarabine Monophosphate Followed by Iodine I 131 Tositumomab for Untreated Low-grade and Follicular Non-Hodgkin's Lymphoma

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and does not necessarily have to have a causal relationship (association) with this treatment. Therefore, an AE was any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not it was considered to be related to the medicinal product. Laboratory abnormalities were recorded as AEs only if they were associated with clinical sequelae and/or required an intervention.

All noxious and unintended responses to a study treatment related to any dose were considered as TRAEs. A response to a study treatment indicates that a causal relationship between a study drug and an adverse event was at least a reasonable possibility, i.e., the relationship cannot be ruled out.

Adverse events were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No adverse event or within normal limits; 1 = Mild adverse event; 2 = Moderate adverse event; 3 = Severe and undesirable adverse event; 4 = Life-threatening or disabling adverse event; 5 = Death related to adverse event.

All of the treatment-related grade 3 (severe and undesirable) and grade 4 (life-threatening or disabling) adverse events experienced by the participants were recorded.

An SAE was defined as any event occurring at any dose that results in any of the following outcomes: death, a life threatening adverse drug experience (at immediate risk of death from the experience as it occurred), inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered to be a serious adverse drug experience when based upon appropriate medical judgment.

All of the treatment-related SAEs experienced by the participants were recorded.

AEs were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No AE or within normal limits; 1 = Mild AE; 2 = Moderate AE; 3 = Severe and undesirable AE; 4 = Life-threatening or disabling AE; 5 = Death related to AE. mm, millimeters; mm\^3, millimeters cubed. Grade 3 and Grade 4 AEs are reported to focus on the most severe AEs.

The administration of murine antibodies may form HAMA. A HAMA assay was performed using the ImmunoSTRIP HAMA IgG enzyme-linked immune absorbent assay by a central laboratory (Covance Classic Laboratory Services, Indianapolis, IN). Fludarabine, a known immunosuppressant, might decrease HAMA production in addition to reducing bone marrow involvement. To be "positive," a participant had to have a positive HAMA assessment at any follow-up visit (Weeks 12 and 25; Months 12, 18, and 24).

Kaplan-Meier estimates of the time to HAMA positivity (days from the first fludarabine dose) was determined for participants who converted to HAMA positivity.

The number of participants with elevated TSH levels is reported. An elevated TSH level indicates that an insufficient amount of the thyroid hormone is being produced. Insufficient thyroid hormone production is known as hypothyroidism. The normal range of TSH is between 0.2 and 6.1 milliunits per liter (mU/L).

Thyroid medication included any prescribed medication for the treatment of thyroid dysfunction.

Nadir was defined as the lowest laboratory value recorded up to 120 days following the therapeutic dose (or dosimetric dose for participants who did not receive the therapeutic dose).

Adverse events were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades (G): 0=No AE or within normal limits; 1=Mild AE; 2=Moderate AE; 3=Severe and undesirable AE; 4=Life-threatening or disabling AE; 5=Death related to AE. ANC (10\^3/mm\^3): G1=1.5 to \<2.0, G2=1.0 to \<1.5, G3=0.5 to \< 1.0, G4=\<0.5. Hemoglobin (g/dL): G1=10.0 to \<12.0, G2=8.0 to \<10.0, G3=6.5 to \<8.0, G4=\< 6.5. Platelets (10\^3/microliter): G1=75 to \<150, G2=50 to \<75, G3=25 to \<50, G4=\<25.

An infection is the colonization of a host organism by a parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease. Colloquially, infections are usually considered to be caused by microscopic organisms or microparasites like viruses, bacteria, and viroids, although larger organisms such as macroparasites and fungi can also infect.

Specimen samples of the body fluid are cultured for testing whether the infectious organism is present and grown in the culture media to assess the growth pattern of the organisms present in the specimen.

The culture results could be positive or negative. The positive culture results indicates that the tested participant have the infection under investigation so therapeutic treatment with anti-infective is required.

Anti-infectives are capable of acting against infection, by inhibiting the spread of an infectious agent or by killing the infectious agent outright. Anti-infective is a general term that encompasses antibacterials, antibiotics, antifungals, antiprotozoans, and antivirals.

Supportive care involves interventions that help the participants to achieve comfort but do not affect the course of a disease.

Supportive care involves interventions that help the participants to achieve comfort but do not affect the course of a disease. Supportive care involved administration of granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), red blood cell (RBC) transfusions, erythropoietin, and platelet transfusions.

CR: Complete resolution of disease-related (DR) radiological abnormalities; disappearance of non-Hodgkin's lymphoma-related signs/symptoms. CCR: Complete resolution of DR symptoms except for residual scar tissue. PR: 50% reduction in the sum of the products of the longest perpendicular diameters of measurable lesions with no new lesions. A confirmed response (resp.) (CR/CCR/PR) had to be confirmed by a consecutive resp. (\>=28 days later) that was the same/better. Individual confirmed resp. data only counts that resp. confirmed by the same resp.; not all possible combinations are represented.

CR: Complete resolution of disease-related (DR) radiological abnormalities; disappearance of non-Hodgkin's lymphoma-related signs/symptoms. CCR: Complete resolution of DR symptoms except for residual scar tissue. PR: 50% reduction in the sum of the products of the longest perpendicular diameters of measurable lesions with no new lesions.

Progression of disease is defined as a 50% increase from nadir of the sum of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be \>2 cm in diameter per radiographic evaluation or \>1 cm in diameter by physical examination. All participants without progression of disease were censored.

Duration of response was defined as the time from the first documented response to the first documented disease progression. Partial Response (PR): 50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions. Responders are the participants with CR, or CCR, or PR.

PD is defined as a 50% increase from nadir of the sum of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be \>2 cm in diameter per radiographic evaluation or \>1 cm in diameter by physical examination.

Time to progression is the time from the treatment start date to the first documented disease progression or death. Disease progression: 50% increase from nadir of the sum of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be \>2 cm in diameter per radiographic evaluation or \>1 cm in diameter by physical examination.

Treatment failure is defined as the occurrence of treatment withdrawal, a decision to seek additional therapy, study removal, progression, alternative therapy for lymphoma, or death.

Time to treatment failure is defined as the time from the treatment start date to the first occurrence of treatment withdrawal, a decision to seek additional therapy, study removal, progression, alternative therapy for lymphoma, or death.

Participants who died during the study period were evaluated for the overall survival endpoint.

Time to death is defined as the time from the treatment start date to the date of death.

GlaxoSmithKline

Participants who received any number of cycles of IV fludarabine monophosphate (25 mg/m\^2/day). Each cycle was administered for 5 days every 5 to 6 weeks.

The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.

TST and Iodine I 131 TST

Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.

Fludarabine/TST and Iodine I 131 TST (Combined Regimen)

Participants received less than 3 cycles of intravenous (IV) fludarabine monophosphate (25 milligrams/meter\^2/day \[mg/m\^2/day\]) for 5 days every 5 to 6 weeks.

Received Less Than 3 Cycles of Fludarabine

Participants (par.) received 3 cycles of IV fludarabine (FL) monophosphate (25 mg/m\^2/day) for 5 days every 5-6 weeks. After receiving FL, par. meeting criteria received the dosimetric dose (DD), administered 6-8 weeks after the 3rd cycle of FL. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Par. received \>=3 doses (4 drops by mouth \[DBM\], 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 DBM, TID) of Lugol's solution, or KI tablets (130 mg BM, once a day) \>=24 hrs prior to administration of the DD and continued daily for 14 days after the therapeutic dose (TD), administered 7-14 days after the DD. The TD was an IV infusion of 450 mg TST over 1 hr, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.

Fludarabine (3 Cycles); TST and Iodine I 131 TST

Total

Age, Continuous

Gender

White

Hispanic

Black

Race/Ethnicity, Customized

GSK Response Center

Participants received 3 cycles of intravenous (IV) fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks.

Intent-to-Treat (ITT)-Exposed Population: all participants who were enrolled into the study and who received at least 1 dose of fludarabine. The data are presented for the subgroup of the ITT-Exposed Population for those participants who received the dosimetric and therapeutic dose of TST/I 131 TST.

Number of Participants With Any Adverse Event (AE)

Number of Participants With Any Treatment-related Adverse Event (TRAE)

Number of Participants With Any Grade 3 or Grade 4 Adverse Event

Number of Participants With Any Treatment-related Grade 3 or Grade 4 Adverse Event

Number of Participants With Any Serious Adverse Event (SAE)

Number of Participants With Any Treatment-related SAE

Absolute neutrophil count <1000 cells/mm^3

White blood cell count <2000 cells/mm^3

Platelet count <50000 cells/mm^3

Hemoglobin <8.0 grams/deciliter

Neutropenia

Anaemia

Leukopenia

Thrombocytopenia

Febrile neutropenia

Myelodysplastic syndrome

Acute myeloid leukaemia

Chronic myelomonocytic leukaemia

Prostate cancer

Squamous cell carcinoma

Nausea

Arrhythmia

Cardiac failure congestive

Left ventricular dysfunction

Myocardial infarction

Autoimmune thyroiditis

Pyrexia

Headache

Dyspnoea

Number of Participants With the Indicated Grade 3 and Grade 4 AEs

Fatigue

Asthenia

Chills

Vomiting

Rash

Ecchymosis

Dizziness

Myalgia

Arthralgia

Cough

Nasal congestion

Oropharyngeal pain

Rhinorrhoea

Sinusitis

Nasopharyngitis

Decreased appetite

Insomnia

Palpitations

Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen

Positive

Negative

Fludarabine/TST and Iodine I 131 TST

ITT-Exposed Population: participants who were evaluable for HAMA (those who did not have a positive HAHA level at Baseline) and those who received dosimetric and therapeutic doses were evaluated.

Number of Participants Who Were Negative for Human Anti-murine Antibodies (HAMA) at Baseline (Study Entry) But Positive or Negative at Weeks 12 and 25 and at Months 12, 18, and 24

Participant 1

Participant 2

ITT-Exposed Population: participants who received dosimetric and therapeutic doses and those who were converted to HAMA positivity were evaluated.

Time to HAMA Positivity From the First TST/I 131 TST Dosimetric Dose for the Participants Achieving HAMA Positivity

Baseline (Week -16), n=35

Week 25, n=33

Week 52, n=33

Week 78, n=33

Week 104, n=33

Week 130, n=33

Week 156, n=33

Week 182, n=33

Week 208, n=33

Week 234, n=33

Week 260, n=33

Week 286, n=33

Week 312, n=33

Week 364, n=33

Week 416, n=33

Week 468, n=33

Week 512, n=33

ITT-Exposed Population: baseline TSH levels were determined for 36 participants. Of 35 participants who received the dosimetric and therapeutic doses of TST/I-131 TST, 2 had elevated TSH at baseline, and 33 were assessed for developing elevated TSH.

Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512

ITT-Exposed Population: all participants who received dosimetric and therapeutic doses were evaluated.

Number of Participants With Thyroid Medication Use Prior to the Therapeutic Dose

Hemoglobin

Platelets

ITT-Exposed Population: all participants who received the dosimetric dose were evaluated.

Time to Nadir for Hematological Parameters: Absolute Neutrophil Count (ANC), Hemoglobin, and Platelets

ITT-Exposed Population: only the 35 participants who received the dosimetric dose were evaluated.

Nadir Values for Absolute Neutrophil Count (ANC)

Nadir Values for Hemoglobin

Nadir Values for Platelet Count

Number of Participants With Any Grade 3 or Grade 4 Toxicity (AE) for Hematological Parameters (Absolute Neutrophil Count [ANC], Hemoglobin, and Platelets)

Duration of Any Grade 3 or Grade 4 Toxicity for Hematological Parameters: Absolute Neutrophil Count (ANC), Hemoglobin, and Platelets

Week 16 Post-Fludarabine Treatment

Week 13 Post-TST Treatment

Number of Participants With Any Infection at Week 16 Post-Fludarabine Treatment and Week 13 Post-TST Treatment Detected by Laboratory Culture of Participant Sample or Investigator Report

Week 16 Post-Fl treatment, Pneumonia, n=11

Week 16 Post-Fl treatment, Other Infections, n=11

Week 13 Post-TST Treatment, Pneumonia, n=9

Week 13 Post-TST Treatment, Other Infections, n=9

ITT-Exposed Population: all participants who received dosimetric and therapeutic doses and those who had an infection were evaluated. A single participant could have had more than one infection. The number analyzed in the category titles reflects the number of participants who had any infection.

Number of the Indicated Type of Infection Reported by Investigator Based on Laboratory Testing at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment

Week 16 Post-Fl treatment, n=11

Week 13 Post-TST Treatment, n=9

ITT-Exposed Population: all participants who received dosimetric and therapeutic doses and those who had an infection were evaluated.

Number of Participants With a Culture Obtained for Infection at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment

Week 16 Post-Fl treatment, n=2

Week 13 Post-TST Treatment, n=1

ITT-Exposed Population: all participants who received dosimetric and therapeutic doses, those who had an infection, and from whom the cultures were obtained were evaluated.

Number of Participants With Positive Culture Results for Infections at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment

Number of Participants With an Anti-infective Administered at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment

ITT-Exposed Population: two participants who received less than 3 cycles of fludarabine did not receive TST treatment, and hence were not evaluated.

Number of Participants Who Received Any Supportive Care After Fludarabine Treatment and After TST Treatment

G-CSF/GM-CSF

RBC transfusion

Erythropoietin

Platelet transfusion

ITT-Exposed Population: two participants who received less than 3 cycles of fludarabine did not receive TST treatment and were not evaluated.

Number of Participants Receiving the Indicated Type of Supportive Care After Fludarabine Treatment and After TST Treatment

Participants with CR, CCR, or PR

Participants with CR or CCR

Participants with PR

ITT-Exposed Population. 2 participants (par.) who received \<3 cycles of fludarabine (fl.) did not receive TST treatment and were not evaluated. Par. evaluable for response were those with \>=1 assessment. Three par. were not evaluable for response. None of the responses could be confirmed after fl. treatment; thus, no data are reported for this arm.

Number of Participants With the Investigator-assessed Confirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR)

ITT-Exposed Population. Participants (par.) evaluable for response were those with \>= 1 response assessment. 2 of 38 par. who received \<3 cycles of fludarabine withdrew from the study and were not evaluable for response. 35 of 38 par. received TST and I 131 TST treatment and were evaluated for response.

Number of Participants With the Investigator-assessed Unconfirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR)

Spots Global Cancer Trial Database for Study of Safety and Efficacy of a Sequential Regimen Consisting of Three Cycles of Fludarabine Followed by Tositumomab and Iodine I 131 Tositumomab

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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