Rituximab, Combination Chemotherapy, and 90-Yttrium Ibritumomab Tiuxetan for Patients With Stage I or II Non-Hodgkin's Lymphoma

NCT00088881 | Terminated Phase 2 Results

• 3 other identifiers: NCI-2012-02957E3402U10CA021115
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial is studying how well giving rituximab together with combination chemotherapy and 90-Yttrium ibritumomab tiuxetan works in treating patients with stage I or stage II lymphoma. Drugs used in chemotherapy, such as prednisone, cyclophosphamide, doxorubicin, and vincristine, work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab and yttrium 90-Yttrium ibritumomab tiuxetan can locate cancer cells and either kill them or deliver radioactive cancer-killing substances to them without harming normal cells. Combining a monoclonal antibody with combination chemotherapy and a radiolabeled monoclonal antibody may kill more cancer cells.

Conditions

Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

Outcome Measures

Primary Outcomes (2)

• Complete Response (CR) +Complete Response/Uncertain (CRu) in Patients Treated With R-CHOP Followed by 90-Yttrium -Zevalin™.

  Response was assessed based upon the criteria from the International Workshop to Standardize Criteria for Non-Hodgkin's Lymphoma (Cheson, 1999). CR is defined as complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease related B-symptoms if present prior to therapy, as well as normalization (normal limits of institutional labs) of those biochemical abnormalities (e.g., LDH) definitely attributed to NHL. CRu is defined as meeting the criteria of CR except one or more of the followings: A residual dominant node (or extra-nodal mass) that is currently \> 1.5 cm in greatest diameter that has decreased by \> 75% from baseline in the product of its diameters. Individual dominant nodes (or extra-nodal masses) that were previously confluent must have decreased by \> 75% in SPD compared with the size of the original mass. Indeterminate bone marrow (increased number or size of aggregates without cytologic or architectural atypia).

  Assessed after 2 cycles of R-CHOP, after completion of R-CHOP, and at Week 12 After 90-Yttrium Zevalin

• Functional CR in Patients Treated With R-CHOP Followed by 90-Yttrium -Zevalin™.

  Patients will be considered a functional CR if they meet the criteria for a CR, or if they meet the criteria for a CRu or partial response (PR) by CT and are PET negative. Please see primary outcome #1 for the definition of CR and CRu. PR is defined as: A decrease of \>50% in the SPD (sum of products of the diameters) of the six largest (or less) dominant nodes or extra-nodal masses. No increase in the size of the liver or the spleen. No unequivocal progression in any non-measurable or non-dominant site. Splenic and hepatic nodules must regress by \>50% in SPD (sum of the products of the diameters). Bone marrow assessment is not relevant for determination of a PR because it is assessable and not measurable disease. No new sites of disease.

  Assessed after 2 cycles of R-CHOP, after completion of R-CHOP, and at Week 12 After 90-Yttrium Zevalin

Secondary Outcomes (2)

• 3-year Time to Treatment Failure (TTF) Rate

  Assessed every 3 months for one year; every 4 months for the second year; then every 6 months for 3 years; then annually to 10 years from patient entry.

• 3-year Overall Survival (OS) Rate

  Assessed every 3 months for 2 years, then every 6 months for 3 years; then annually to 10 years from patient entry.

Study Arms (1)

Treatment

EXPERIMENTAL

R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone): Patients receive R-CHOP every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response after 2 courses receive 2 additional courses. Patients achieving a partial response, uncertain CR, or stable disease receive 4 additional courses. Patients with progressive disease go off study. Zevalin™Radioimmunotherapy: Beginning no more than 9 weeks after the last course of R-CHOP, patients receive rituximab IV on day 1 followed by indium In 111 ibritumomab tiuxetan IV over 10 minutes for imaging studies. Patients then receive rituximab IV followed by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 8. Radiation therapy: Patients with residual disease by CT scan or positron emission tomography (PET) scan after 12 weeks after radioimmunotherapy undergo conventional involved-field radiotherapy.

Biological: rituximab; Drug: prednisone; Drug: cyclophosphamide; Drug: doxorubicin; Drug: vincristine; Radiation: indium In 111 ibritumomab tiuxetan; Radiation: radiation therapy; Procedure: positron emission tomography

Interventions

rituximab BIOLOGICAL

Given IV

Also known as: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan

Treatment

prednisone DRUG

Given orally

Also known as: DeCortin, Deltra

Treatment

cyclophosphamide DRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana

Treatment

doxorubicin DRUG

Given IV

Also known as: ADM, ADR, Adria, Adriamycin PFS, Adriamycin RDF

Treatment

vincristine DRUG

Given IV

Also known as: leurocristine sulfate, VCR, Vincasar PFS

Treatment

indium In 111 ibritumomab tiuxetan RADIATION

Given IV

Also known as: IDEC-In2B8

Treatment

radiation therapy RADIATION

Undergo radiotherapy

Also known as: irradiation, radiotherapy, therapy, radiation

Treatment

positron emission tomography PROCEDURE

Undergo PET scans

Also known as: FDG-PET, PET, PET scan, tomography, emission computed

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed diagnosis of diffuse large cell lymphoma
• Patients must be stage I or II (Modified Ann Arbor staging)
• Baseline measurements and evaluations must be obtained within 4 weeks of registration to the study; abnormal PET scans will not constitute evaluable disease unless verified by CT scan or other appropriate imaging; patients must have at least one objective measurable disease parameter (a lesion with at least 1 dimension \> 1.5 cm); or if they are stage 1
• Stage I patients must have at least one of the following risk factors:
• Age \>= 60 years
• Bulky disease (\>= 5 cm in at least one dimension)
• Elevated Lactate Dehydrogenase (LDH) above institutional upper limit of normal
• Eastern Cooperative Oncology Group (ECOG) performance status = 2
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Absolute neutrophil count \>= 1500/mm\^3 (includes neutrophils and bands)
• Platelet count \>= 100,000/mm\^3
• Creatinine \< 2.0 mg/dl
• Total bilirubin \< 2 mg/dl (may be up to 3.0 mg/dl if due to liver involvement by lymphoma); patients with elevated total bilirubin should have a direct bilirubin checked; if the direct bilirubin is normal there is no need for a dose reduction
• Patients must have left ventricular ejection fraction (LVEF) of \> 45%
• Patients must be tested for hepatitis B (HBV) surface antigen within 2 weeks of registration

You may not qualify if:

• Prior chemotherapy, radiation therapy, radioimmunotherapy, or immunotherapy; a short course (=\< 14 days prior to registration) of corticosteroids is allowed
• Evidence of other malignancy:
• Prior chemotherapy or prior radiation therapy for other malignancies
• Currently receiving hormone therapy or chemotherapy for another malignancy even if the treatment is being provided in the adjuvant treatment setting, i.e. with no evidence of the original other malignancy
• Adjuvant hormonal therapy must have been discontinued \> 3 months before entering this study
• Patients are eligible if they meet the following conditions: (a) treated carcinoma-in-situ of the cervix; (b) treated squamous cell or basal cell skin cancer; or (c) any other surgically cured malignancy from which the patient has been disease free for at least 3 years
• Pregnant or breast feeding, as there would be radiation exposure to the fetus or child; a negative pregnancy test is required =\< 1 week prior to registration for women of childbearing potential (WOCBP). Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception
• Known central nervous system (CNS) lymphoma, testicular lymphoma, or vitreous lymphoma
• Known HIV infection. The safety of Zevalin™ in this population has not been tested at this time
• Serious coexisting medical condition or active infection which would compromise the ability to deliver standard R-CHOP chemotherapy
• Evidence of myelodysplasia on bone marrow aspiration and biopsy

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Eastern Cooperative Oncology Group

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Lymphoma, B-Cell, Marginal Zone; Lymphoma, Large B-Cell, Diffuse; Waldenstrom Macroglobulinemia

Interventions

Rituximab; Prednisone; Cyclophosphamide; Doxorubicin; Vincristine; Indium; Radiotherapy; Radiation; Magnetic Resonance Spectroscopy; 2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazole

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Metals, Heavy; Elements; Inorganic Chemicals; Metals; Therapeutics; Physical Phenomena; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Results Point of Contact

• Title: Study Statistician
• Organization: ECOG Statistical Office

617-632-3012

Study Officials

• Thomas Witzig

  Eastern Cooperative Oncology Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2004
• First Posted: August 5, 2004
• Study Start: December 1, 2004
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: May 25, 2017
• Results First Posted: February 18, 2015

Record last verified: 2017-04

Locations

US (1)