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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:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00770224
First received: October 8, 2008
Last updated: June 18, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Lymphoma
Biological: rituximab
Biological: tositumomab
Drug: cyclophosphamide
Drug: doxorubicin
Drug: prednisone
Drug: vincristine
Radiation: tositumomab
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: 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

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • 3-year progression-free survival (PFS) [ Time Frame: 0-3 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 5-year Progression-free Survival [ Time Frame: 0-5 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 87
Study Start Date: April 2009
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Biological: rituximab Biological: tositumomab Drug: cyclophosphamide Drug: doxorubicin Drug: prednisone Drug: vincristine Radiation: tositumomab
Other Name: iodine I 131 tositumomab

Detailed Description:

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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00770224

  Show 114 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Investigators
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
  More Information

Additional Information:
No publications provided

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00770224     History of Changes
Other Study ID Numbers: CDR0000615104, S0801, U10CA032102
Study First Received: October 8, 2008
Last Updated: June 18, 2014
Health Authority: United States: Federal Government

Keywords provided by Southwest Oncology Group:
contiguous stage II grade 1 follicular lymphoma
contiguous stage II grade 2 follicular lymphoma
contiguous stage II grade 3 follicular lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Antibodies, Monoclonal
Cyclophosphamide
Doxorubicin
Iodine-131 anti-B1 antibody
Liposomal doxorubicin
Prednisone
Rituximab
Vincristine
Alkylating Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Enzyme Inhibitors
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on November 20, 2014