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S1001 PET-Directed Therapy in Treating Patients With Limited-Stage Diffuse Large B-Cell Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Southwest Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT01359592
First received: May 21, 2011
Last updated: February 17, 2014
Last verified: February 2014
  Purpose

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone, work in different ways to stop cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill cancer 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. Radiolabeled monoclonal antibodies, such as yttrium Y 90 ibritumomab tiuxetan, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Comparing results of diagnostic procedures, such as PET scan and CT scan, done before, during, and after chemotherapy may help doctors predict a patient's response to treatment and help plan the best treatment.

PURPOSE: This phase II trial studies how well PET-directed chemotherapy works in treating patients with limited-stage diffuse large B-cell lymphoma.


Condition Intervention Phase
Lymphoma
Biological: rituximab
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: prednisone
Drug: vincristine sulfate
Other: R-CHOP regimen
Other: laboratory biomarker analysis
Radiation: fludeoxyglucose F 18
Radiation: selective external radiation therapy
Radiation: yttrium Y 90 ibritumomab tiuxetan
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of PET-Directed Therapy for Limited Stage Diffuse Large B-Cell Lymphoma (DLBCL)

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • Five-year PFS rate of patients with DLBCL [ Time Frame: 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. Patients last known to be alive without report of progression or relapse are censored at date of last contact.


Secondary Outcome Measures:
  • PFS within the PET+ and PET- subgroups of patients with newly diagnosed limited-stage DLBCL [ Time Frame: 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. Patients last known to be alive without report of progression or relapse are censored at date of last contact.

  • Toxicity of protocol treatments [ Time Frame: Up to 4 months ] [ Designated as safety issue: Yes ]
    Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.

  • Overall survival of patients with DLBCL [ Time Frame: 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 are censored at date of last contact.

  • Association of germinal center B-cell subtype (GCB) vs stromal-1 vs stromal-2 gene expression signatures with PFS or overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Formalin-fixed, paraffin-embedded tissue from the diagnostic biopsy is collected and used to determine germinal center B-cell (GCB) phenotype. GCB subtype of DLBCL is defined by gene-expression profiling that is performed using quantitative nuclease protection assay (qNPA).


Estimated Enrollment: 155
Study Start Date: September 2011
Estimated Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: PET Negative: R-CHOP
R-CHOP x 3 Cycles
Biological: rituximab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisone Drug: vincristine sulfate Other: R-CHOP regimen Other: laboratory biomarker analysis
Experimental: PET Positive: IFRT +Zevalin
Standard IFRT+ Zevalin IV per ABW
Biological: rituximab Other: laboratory biomarker analysis Radiation: fludeoxyglucose F 18 Radiation: selective external radiation therapy Radiation: yttrium Y 90 ibritumomab tiuxetan

Detailed Description:

OBJECTIVES:

Primary

  • To assess the 5-year progression-free survival (PFS) rate in patients with newly diagnosed limited-stage diffuse, large B-cell lymphoma (DLBCL) using positron emission tomography (PET)/CT scan to direct therapy after 3 courses of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP).

Secondary

  • To evaluate PFS within the PET-positive (+) and PET-negative (-) subgroups of patients with newly diagnosed limited-stage DLBCL.
  • To evaluate toxicity of the protocol treatments in this patient population.
  • To evaluate the response probability in this patient population.
  • To evaluate overall survival in the overall population, and within the PET+ and PET- subgroups.
  • To estimate the rate of upstaging at baseline by PET/CT at baseline among patients newly diagnosed with limited-stage DLBCL by CT imaging and to describe outcomes in patients upstaged by PET/CT at baseline to advanced DLBCL.
  • To describe outcomes in the subgroup of patients upstaged by PET/CT.
  • To evaluate the association of germinal center B-cell subtype (GCB) vs stromal-1 vs stromal-2 gene expression signatures with PFS or overall survival.

OUTLINE: This is a multicenter study. Patients are stratified according to whether the patient was upstaged to advanced stage DLBCL, based on local review of the baseline PET/CT (yes vs no).

Chemotherapy: Patients receive R-CHOP comprising rituximab IV, cyclophosphamide IV over 30-60 minutes, vincristine sulfate IV, and doxorubicin hydrochloride IV on day 1, and prednisone orally on days 1-5. Treatment repeats every 21 days for 3* courses. NOTE: *Patients found to have advanced stage DLBCL based on local review of the baseline PET scan receive 6 courses of R-CHOP.

FDG/PET - Radiotherapy: Patients undergo fludeoxyglucose F 18 positron emission tomography (FDG-PET)/CT scan at baseline, on days 15-18 of course 3, and at 12 weeks after completion of course 3. Patients with complete response (PET scan negative) receive one additional course of R-CHOP as above. Patients with partial response (PET scan positive) undergo involved-field radiotherapy (IFRT) 5 days a week for approximately 4-5 weeks.

Monoclonal antibody: Beginning 3-6 weeks after completion of IFRT, patients receive yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes and rituximab IV on day 1 and on day 7, 8, or 9.

Patients may undergo blood sample collection at baseline for correlative studies. Bone marrow tissue samples may be also collected for correlative studies.

After completion of study therapy, patients are followed up every 6 months for 2 years and then yearly for 5 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Patients must have biopsy-proven diffuse large B-cell lymphoma (DLBCL)

    • Adequate sections or a paraffin block from the original diagnostic specimen must be submitted for review by the lymphoma pathology group
    • Lymphoma must express CD20 antigen by either flow cytometry using anti-CD20 antibodies or by immunoperoxidase staining of paraffin sections
    • Patients with primary mediastinal lymphoma or testicular lymphoma are not eligible
  • Patients must have non-bulky stage I or II disease by Ann Arbor classification

    • This staging excludes FDG-PET evaluation
    • Patients who have stage I or II non-bulky disease on diagnostic CT scan, but are upstaged to stage III or IV based on FDG-PET evaluation, are also eligible
  • Patients must have a diagnostic quality contrast-enhanced CT scan of the chest, abdomen, and pelvis AND baseline FDG-PET scan performed within 28 days prior to registration

    • Low-resolution "localization" CT scans performed as part of a combined PET/CT scan are not adequate for enrollment or response determination on this protocol
    • If a patient has an allergy to CT contrast, then a non-enhanced CT will be acceptable
  • Patients must not have clinical evidence of central nervous system (CNS) involvement by lymphoma

    • Any laboratory or radiographic tests performed to assess CNS involvement must be negative and must be performed within 42 days prior to registration
  • Patients may have either measurable or evaluable limited-stage DLBCL

    • Patients rendered free of measurable or evaluable disease by virtue of biopsy (resection) are also eligible
    • If patient has measurable disease it must be documented on the Lymphoma Baseline Tumor Assessment Form (Form #15187)
    • All measurable disease must be assessed within 28 days prior to registration
    • Patients with non-measurable disease in addition to measurable disease must have all non-measurable disease assessed within 42 days prior to registration
  • Patients must have a unilateral or bilateral bone marrow biopsy performed within 42 days prior to registration

PATIENT CHARACTERISTICS:

  • Zubrod performance status 0-2
  • Absolute neutrophil count (ANC) ≥ 1,000/mm³
  • Platelet count ≥ 100,000/mm³
  • Total bilirubin ≤ 2 times upper limit of normal (ULN) (unless due to Gilbert syndrome)
  • Patients must not be pregnant or nursing
  • Women/men of reproductive potential must have agreed to use an effective contraceptive method during the study period
  • Patients must not be known to be HIV-positive
  • No other prior malignancy is allowed except for the following:

    • Adequately treated basal cell or squamous cell skin cancer
    • In situ cervical cancer
    • Adequately treated stage I or II cancer from which the patient is currently in complete remission
    • Any other cancer from which the patient has been disease-free for 5 years

PRIOR CONCURRENT THERAPY:

  • Patients must not have received prior chemotherapy, radiotherapy, or antibody therapy for lymphoma
  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: NCT01359592

Contacts
Contact: Megan Hardin 2106148808 ext 1014 mhardin@swog.org
Contact: Dana Sparks, MAT 2106148808 ext 1004 dsparks@swog.org

  Show 240 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Principal Investigator: Daniel O. Persky, MD Yale University
  More Information

Additional Information:
No publications provided

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT01359592     History of Changes
Other Study ID Numbers: CDR0000700624, S1001, U10CA032102
Study First Received: May 21, 2011
Last Updated: February 17, 2014
Health Authority: United States: Federal Government

Keywords provided by Southwest Oncology Group:
stage I adult diffuse large cell lymphoma
contiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Rituximab
Doxorubicin
Prednisone
Vincristine
Antibodies, Monoclonal
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on July 26, 2014