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S0801 Iodine I 131 Tositumomab, Rituximab, and Combination Chemotherapy in Previously Untreated Stage II, Stage III, or Stage IV Follicular Non-Hodgkin Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00770224
First Posted: October 9, 2008
Last Update Posted: July 18, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Southwest Oncology Group
October 8, 2008
October 9, 2008
July 18, 2017
April 2009
April 2017   (Final data collection date for primary outcome measure)
3-year progression-free survival (PFS) [ Time Frame: 0-3 years ]
Measured from date of registration to date of first observation of progressive disease or death due to any cause. Progressive disease is ≥ 50% increase in the sum of products of greatest diameters (SPD) of target measurable nodal lesions over the smallest sum observed (over baseline if no decrease during therapy), or ≥ 50% increase in the greatest transverse diameter (GTD) of any node > 1 cm in shortest axis, or ≥ 50% increase in the SPD of other target measurable lesions (e.g., splenic or hepatic nodules) over the smallest sum observed. Appearance of any new bone marrow involvement; appearance of a new lesion/site; lymph nodes with the long axis is > 1.5 cm, or if the both the long and short axes are > 1 cm; in patients with no pretreatment PET scan or when the PET scan was positive before therapy, lesions should be PET positive; or death due to disease without prior documentation of progression.
3-year progression-free survival (PFS)
Complete list of historical versions of study NCT00770224 on ClinicalTrials.gov Archive Site
  • 5-year Progression-free Survival [ Time Frame: 0-5 years ]
    Measured from date of registration to date of first observation of progressive disease or death due to any cause. Progressive disease is ≥ 50% increase in the sum of products of greatest diameters (SPD) of target measurable nodal lesions over the smallest sum observed (over baseline if no decrease during therapy), or ≥ 50% increase in the greatest transverse diameter (GTD) of any node > 1 cm in shortest axis, or ≥ 50% increase in the SPD of other target measurable lesions (e.g., splenic or hepatic nodules) over the smallest sum observed. Appearance of any new bone marrow involvement; appearance of a new lesion/site; lymph nodes with the long axis is > 1.5 cm, or if the both the long and short axes are > 1 cm; in patients with no pretreatment PET scan or when the PET scan was positive before therapy, lesions should be PET positive; or death due to disease without prior documentation of progression.
  • 5-year overall survival [ Time Frame: 0-5 years ]
    Measured from date of registration to date of death due to any cause. Patients last known to be alive and are censored at date of last contact.
  • Response rate [ Time Frame: up to 1 year while on treatment, or up to maximum of 7 years on protocol, or time of disease progression ]
    Complete (CR), complete unconfirmed (CRU) and partial responses (PR). CR is complete disappearance of all measurable and non-measurable disease with the exception of the following. PET must be negative if no pretreatment PET scan or when the PET was positive before therapy. If the PET scan was negative before therapy, all nodal masses must have regressed. no new lesions; previously enlarged organs must have regressed in size; and if bone marrow positive at baseline, it must be negative. PR is ≥ 50% decrease in sum of products of greatest diameters (SPD) for up to six identified dominant lesions identified at baseline; no new lesions; no increase in the size of liver, spleen or other nodes; and splenic and hepatic nodules must have regressed in size by at least 50% in SPD. In patients with no pretreatment PET scan or when the PET scan was positive before therapy, PET should be positive in at least one previously involved site.
  • Safety profile as assessed by NCI CTCAE v4.0 [ Time Frame: up to 5 years (1 year induction + 4 years maintenance therapy) or time of disease progression ]
    Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.
  • 5-year PFS
  • 5-year overall survival
  • Response
  • Safety profile as assessed by NCI CTCAE v3.0
Not Provided
Not Provided
 
S0801 Iodine I 131 Tositumomab, Rituximab, and Combination Chemotherapy in Previously Untreated Stage II, Stage III, or Stage IV Follicular Non-Hodgkin Lymphoma
A Phase II Study of Iodine-131-Labeled Tositumomab in Combination With Cyclophosphamide, Doxorubicin, Vincristine, Prednisone and Rituximab Therapy for Patients With Advanced Stage Follicular Non-Hodgkin's Lymphoma

RATIONALE: Radiolabeled monoclonal antibodies, such as iodine I 131 tositumomab, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving a radiolabeled monoclonal antibody together with rituximab and combination chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying the side effects of giving iodine I 131 tositumomab together with rituximab and combination chemotherapy and to see how well it works in treating patients with previously untreated stage II, stage III, or stage IV follicular non-Hodgkin lymphoma.

OBJECTIVES:

  • To evaluate the response rate in patients with previously untreated stage II-IV follicular non-Hodgkin lymphoma treated with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP) in combination with iodine I 131 tositumomab.
  • To evaluate the toxicity of this regimen in these patients.
  • To estimate the 3-year progression-free survival rate in patients treated with this regimen.
  • To estimate the 5-year progression-free and overall survival rate in patients treated with this regimen.
  • To assess the safety profile of this regimen in these patients.

OUTLINE: This is a multicenter study.

  • Induction therapy: Patients receive R-CHOP* comprising rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with at least stable disease then proceed to consolidation therapy.

NOTE: *Patients receive R-CHOP in courses 1-4 and CHOP alone in courses 5 and 6.

  • Consolidation therapy: Within 12 weeks after completion of induction therapy, patients receive tositumomab IV over 1 hour followed by a dosimetric dose of iodine I 131 tositumomab IV over 20 minutes. Patients then undergo whole body gamma camera scans over a 1-week period to determine the rate of total body clearance of radioactivity and the therapeutic dose of iodine I 131 tositumomab. Within 7-14 days after the dosimetric dose, patients receive tositumomab IV over 1 hour followed by a therapeutic dose of iodine I 131 tositumomab IV over 20 minutes. Patients with at least stable disease then proceed to maintenance therapy.
  • Maintenance therapy: Beginning approximately 1 year after study entry and no more than 28 days after restaging, patients receive rituximab IV every 3 months for up to 4 years (16 courses) in the absence of disease progression or unacceptable toxicity.

After completion of maintenance therapy, patients are followed annually for up to 7 years. Patients who do not complete maintenance therapy are followed every 6 months for 2 years and then annually for up to 7 years.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Lymphoma
  • Biological: rituximab
  • Biological: tositumomab
  • Drug: cyclophosphamide
  • Drug: doxorubicin
  • Drug: prednisone
  • Drug: vincristine
  • Radiation: tositumomab
    Other Name: iodine I 131 tositumomab
Experimental: R-CHOP, tositumomab and rituximab

Cyclophosphamide 750 mg/m2 IV Day 1 Doxorubicin 50 mg/m2 IV Day 1 Vincristine 1.4 mg/m2 IV Day 1 Prednisone 100 mg PO Days 1-5 Rituximab 375 mg/m2 IV Day 1 Q 21 Days x 6 Cycles

Patients are restaged by CT scan. Unlabeled tositumomab antibody 450 mg IV within 12 after Cycle 6 of CHOP. Dosimetric dose 35 mg IV after infusion of unlabeled tositumomab antibody. Unlabeled tositumomab antibody 450 mg IV 7-14 days after dosimetric dose. Therapeutic dose 35 mg IV after infusion of unlabeled tositumomab antibody.

Rituximab 375 mg/m2 IV q 3 months x 4 years beginning 1 year after registration.

Interventions:
  • Biological: rituximab
  • Biological: tositumomab
  • Drug: cyclophosphamide
  • Drug: doxorubicin
  • Drug: prednisone
  • Drug: vincristine
  • Radiation: tositumomab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
87
December 2017
April 2017   (Final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Histologically confirmed* grade 1, 2, or 3 follicular B-cell non-Hodgkin lymphoma meeting the following criteria:

    • Bulky stage II or stage III or IV disease
    • Diffuse large cell component must be < 25% of the biopsy
    • Confirmed cluster of differentiation antigen 20 (CD20) antigen-positive disease NOTE: *Needle aspiration or cytology are not considered adequate for pathology review
  • Patient must have unilateral or bilateral bone marrow aspirate and biopsy performed within 42 days

    • Positive biopsy performed > 42 days but < 6 months allowed
  • Previously untreated disease
  • Bidimensionally measurable disease
  • No clinical evidence of central nervous system (CNS) involvement by lymphoma

PATIENT CHARACTERISTICS:

  • Zubrod performance status 0-2
  • Cardiac ejection fraction ≥ 45% by multigated acquisition scan (MUGA) or ECHO
  • No significant cardiac abnormalities
  • No known HIV positivity
  • No requirement for continuous supplemental oxygen therapy
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer from which the patient is currently in complete remission
  • Not pregnant or nursing
  • Fertile patients must use effective contraception during and for 12 months after completion of maintenance therapy

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy, radiotherapy, or antibody therapy for lymphoma
  • No prior solid organ transplantation
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00770224
CDR0000615104
S0801 ( Other Identifier: SWOG )
U10CA032102 ( U.S. NIH Grant/Contract )
No
Not Provided
Not Provided
Southwest Oncology Group
Southwest Oncology Group
National Cancer Institute (NCI)
Study Chair: Jonathan W. Friedberg, MD James P. Wilmot Cancer Center
Study Chair: Oliver W. Press, MD, PhD Fred Hutchinson Cancer Research Center
Study Chair: Lisa Rimsza, MD University of Arizona
Southwest Oncology Group
July 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP