Rituximab, Fludarabine, Cyclophosphamide, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Relapsed B-Cell Non-Hodgkin's Lymphoma

NCT00397800 | Unknown Phase 1

• 3 other identifiers: CDR0000515982KRDI-TUM-R-F-015-V-0030-IEU-20633
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 12

Brief Summary

RATIONALE: 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 fludarabine and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. 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. Giving rituximab and chemotherapy together with yttrium Y 90 ibritumomab tiuxetan may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of yttrium Y 90 ibritumomab tiuxetan when given together with rituximab, fludarabine, and cyclophosphamide and to see how well they work in treating patients with relapsed B-cell non-Hodgkin's lymphoma.

Conditions

Lymphoma

Keywords

recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; Waldenstrom macroglobulinemia; recurrent mantle cell lymphoma; recurrent marginal zone lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicity

Secondary Outcomes (2)

• Response

• Survival

Interventions

rituximab BIOLOGICAL

cyclophosphamide DRUG

fludarabine phosphate DRUG

yttrium Y 90 ibritumomab tiuxetan RADIATION

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed CD20-positive B-cell non-Hodgkin's lymphoma (NHL), including any of the following subtypes: * Indolent NHL, including any of the following: * Follicular * Lymphoplasmacytoid * Marginal zone * Mantle cell NHL * Transformed B-cell NHL * In at least first relapse with an indication for systemic antineoplastic treatment, as defined by the following: * Local or constitutional (B-) symptoms * Hypersplenism due to splenic involvement * Bulky disease (\> 7.5 cm in diameter) * Impending medical problems derived from rapid disease progression within the past 6 months, as defined by an observed or anticipated \> 50% increase in the sum of the areas calculated from multiplying the greatest perpendicular diameters of each lesion * Measurable lesions of lymphoma infiltration * Medically ineligible for high-dose treatment followed by autologous stem cell support * Adequate bone marrow cellularity (\> 15% of marrow area covered by hematopoiesis) * No CNS, leptomeningeal, spinal cord, or testes lymphoma involvement * No lymphoma lesion mandating emergency radiotherapy * No clinical, cytological, cytogenetic, or histopathologic indication of myelodysplastic syndrome * If there is bone marrow infiltration detected prior to chemoimmunotherapy, patient must undergo a repeat bone marrow biopsy prior to planned treatment with radioimmunotherapy to verify the level of bone marrow infiltration is \< 25% PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Life expectancy ≥ 3 months * Absolute neutrophil count \> 1,500/mm³ * Platelet count \> 150,000/mm³ * Hemoglobin \> 9 g/dL * Creatinine \< 1.5 times upper limit of normal (ULN) * Bilirubin \< 2 times ULN * ALT and AST \< 2 times ULN * Albumin \> 2.5 g/dL * INR \< 1.5 * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for ≥ 12 months after completion of study treatment * No concurrent severe and/or uncontrolled medical disease that would preclude study compliance, including any of the following: * Uncontrolled diabetes * Congestive heart failure * Chronic renal disease * Active uncontrolled infection * No bleeding risks or disorders, including any of the following: * CNS abnormalities suggesting an increased susceptibility for hemorrhage, including recent history of stroke as demonstrated by cranial contrast-enhanced CT scan * Severe arrhythmia or uncontrolled hypertension * Myocardial infarction within the past 6 months * Diabetic retinopathy with history of symptomatic hemorrhage * Known and potentially active gastrointestinal bleeding foci * Concurrent anticoagulant medication that must be continued even with platelet count \< 20,000/mm³ (e.g., following mitral valve replacement, anti-phospholipid syndrome, or recurrent venous thromboembolism) * Other congenital or acquired hemorrhagic diatheses * No ongoing autoimmune hemolytic anemia * No known presence of anti-murine antibody reactivity * No known hypersensitivity to murine or chimeric antibodies or proteins * No known HIV infection * No psychiatric illness that would preclude study requirements * No other malignant disorder within the past 10 years except basal cell carcinoma of the skin or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Recovered from prior therapy * No more than 4 prior systemic anti-lymphoma regimens (including single-agent rituximab) * At least 2 months since prior systemic anti-lymphoma treatment (including single-agent rituximab) * No prior radioimmunotherapy * No prior autologous or allogeneic hematopoietic stem cell transplantation * No prior treatment with purine analogues that has not resulted in remission for \> 1 year * No prior anti-CD20 radioimmunoconjugate therapy * More than 5 years since prior radiotherapy to extensive fields covering lymph node regions on both sides of the diaphragm or \> 50% of the spinal column * More than 4 weeks since prior surgery * No concurrent oral anticoagulant therapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Technical University of Munich: lead

Study Sites (12)

Medizinische Klinik, Klinikum Augsburg

Augsburg, D-86156, Germany

Location

Medizinische Klinik III - Universitaetsklinikum Erlangen

Erlangen, D-91054, Germany

Location

Universitaetsklinikum Goettingen

Göttingen, D-37075, Germany

Location

Universitaetsklinikum Schleswig-Holstein - Campus Luebeck

Lübeck, D-23538, Germany

Location

Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg

Magdeburg, D-39120, Germany

Location

Universitatsklinik Mainz

Mainz, D-55101, Germany

Location

LMU-Klinikum Grosshadern

Munich, D-81366, Germany

Location

Klinikum Rechts Der Isar - Technische Universitaet Muenchen

Munich, D-81675, Germany

Location

Klinikum der Universitaet Regensburg

Regensburg, D-93042, Germany

Location

Universitaetsklinikum Tuebingen

Tübingen, D-72076, Germany

Location

Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm

Ulm, D-89081, Germany

Location

Medizinische Klinik und Poliklinik II - Universitaetsklinikum Wuerzburg

Würzburg, D-97080, Germany

Location

MeSH Terms

Conditions

Lymphoma; Lymphoma, Follicular; Waldenstrom Macroglobulinemia; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone

Interventions

Rituximab; Cyclophosphamide; fludarabine phosphate; ibritumomab tiuxetan

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Christian Peschel, MD

  Technical University of Munich

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2006
• First Posted: November 10, 2006
• Study Start: June 1, 2005
• Primary Completion: May 1, 2008
• Study Completion: May 1, 2013
• Last Updated: August 28, 2012

Record last verified: 2012-08

Locations

DE (12)