Radiolabeled Monoclonal Antibody Therapy and High-Dose Chemotherapy Followed By Autologous Peripheral Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

NCT00058292 | Completed Phase 1

• 3 other identifiers: NU 99H11NU-99H11IDEC-NU99H11
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 3

Brief Summary

RATIONALE: Radiolabeled monoclonal antibodies such as yttrium Y90 ibritumomab tiuxetan can locate cancer cells and deliver radioactive cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining yttrium Y90 ibritumomab tiuxetan and chemotherapy with autologous stem cell transplant may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: This phase I trial is studying how well giving yttrium Y90 ibritumomab tiuxetan with high-dose chemotherapy followed by autologous stem cell transplant work in treating patients with relapsed or refractory non-Hodgkin's lymphoma.

Conditions

Lymphoma

Keywords

recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult Burkitt lymphoma; recurrent adult immunoblastic large cell lymphoma; recurrent mantle cell lymphoma; recurrent adult lymphoblastic lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent marginal zone lymphoma; recurrent small lymphocytic 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)

• Determine the maximum tolerated dose of absorbed radiation to critical organs delivered with this combination of study treatments

  Dose limiting toxicities observed during and up to 30 days after the last study treatment resulting in the determination of the maximum tolerated dose of absorbed radiation to critical organs delivered by Y2B8 in combination with high-dose BEAM chemotherapy with autologous mobilized peripheral blood progenitor cell transplant

  From first study treatment until 30 days after last study treatment.

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Biological: filgrastim; Biological: rituximab; Drug: Carmustine; Drug: cytarabine; Drug: etoposide; Drug: melphalan; Procedure: peripheral blood stem cell transplantation; Radiation: yttrium Y 90 ibritumomab tiuxetan

Interventions

filgrastim BIOLOGICAL

Given at a dose of 5 μg/kg, subcutaneously daily, beginning on Day 0 (stem cell transplant day) until white blood cells measure greater than 1500/ul.

Also known as: G-CSF, granulocyte colony stimulating factor

Treatment Arm

rituximab BIOLOGICAL

Intravenous infusion of 250 mg/m2 on treatment days -22 and -14 (day 0 = stem cell transplant).

Treatment Arm

Carmustine DRUG

Part of high dose BEAM chemotherapy given on study (a combination of carmustine, etoposide, cytarabine, and melphalan). Carmustine is given at a dose of 300 mg/m2 intravenous infusion over a 2 hour period on treatment day -6 (Day 0 = stem cell transplant).

Also known as: BCNU

Treatment Arm

cytarabine DRUG

Part of high dose BEAM chemotherapy given on study (a combination of carmustine, etoposide, cytarabine, and melphalan). Cytarabine is given at a dose of 100 mg/m2 intravenous infusion over a 1 hour period, every 12 hours on treatment days -5, -4, -3, and -2, for a total of 8 doses (Day 0 = stem cell transplant).

Also known as: Cytosar-U, Arabinosyl, Ara-C, cytosine arabinoside

Treatment Arm

etoposide DRUG

Part of high dose BEAM chemotherapy given on study (a combination of carmustine, etoposide, cytarabine, and melphalan). Etoposide is given at a dose of 100 mg/m2 intravenous infusion over a 2 hour period every 12 hours on treatment days -5, -4, -3, and -2, for a total of 8 doses (Day 0 = stem cell transplant).

Also known as: VP-16, VP-16-213, Vepesid, Epidophylotoxin

Treatment Arm

melphalan DRUG

Part of high dose BEAM chemotherapy given on study (a combination of carmustine, etoposide, cytarabine, and melphalan). Melphalan is given at a dose of 140 mg/m2 as an intravenous infusion over a 1 hour period on treatment day -1 (Day 0 = stem cell transplant).

Treatment Arm

peripheral blood stem cell transplantation PROCEDURE

On day 0, a minimum of 2.0 X 106 CD34+ cells/kg unselected peripheral blood progenitor cells (PBPC) will be reinfused following institutional guidelines for the reinfusion procedure.

Treatment Arm

yttrium Y 90 ibritumomab tiuxetan RADIATION

Patients will receive 90Y2B8 at a variable dose on treatment day -14 (Day 0 = stell cell transplant). The initial dose calculated to deliver no more than 100 cGy to critical organs (liver, lung). Doses will be escalated based on cohort of enrollment.

Treatment Arm

Eligibility Criteria

• Age: 17 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed B-cell non-Hodgkin's lymphoma * Relapsed or refractory disease * CD20-positive disease * Must have received at least 1 prior treatment regimen * Complete remission with prior conventional salvage chemotherapy is allowed * No more than 25% lymphoma in bone marrow * No circulating malignant cells on blood smear * No CNS involvement by lymphoma * No HIV- or AIDS-related lymphoma PATIENT CHARACTERISTICS: Age * Over 17 Performance status * ECOG 0-2 Life expectancy * At least 3 months Hematopoietic * Platelet count at least 100,000/mm\^3 * Absolute neutrophil count at least 1,500/mm\^3 Hepatic * Transaminases less than 2 times normal Renal * Creatinine clearance greater than 50 mL/min Cardiovascular * LVEF at least 45% Pulmonary * Corrected DLCO at least 70% of predicted * FEV\_1 or FVC greater than 60% Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No active infection * No serious nonmalignant disease or other condition that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy * More than 4 weeks since prior rituximab and recovered * No other prior murine antibodies * No prior stem cell transplantation * No prior radioimmunoconjugate therapy Chemotherapy * See Disease Characteristics * More than 6 weeks since prior nitrosoureas or mitomycin and recovered Endocrine therapy * No concurrent systemic corticosteroids Radiotherapy * Recovered from prior radiotherapy * No prior external beam irradiation to more than 25% of the active bone marrow Surgery * More than 4 weeks since prior major surgery and recovered Other * More than 3 weeks since prior anticancer therapy

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

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Hematology-Oncology Associates of Illinois

Chicago, Illinois, 60611-2998, United States

Location

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, 60611-3013, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• Winter J, Inwards D, Spies S, et al.: Zevalin® (90YZ) doses >.5 mCi/kg may be combined with high-dose beam and autotransplant (ASCT). [Abstract] Ann Oncol 16 (Suppl 5): A-215, v100, 2005.

  RESULT

MeSH Terms

Conditions

Lymphoma; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Burkitt Lymphoma; Lymphoma, Large-Cell, Immunoblastic; Lymphoma, Mantle-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, B-Cell, Marginal Zone; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Filgrastim; Granulocyte Colony-Stimulating Factor; Rituximab; Carmustine; Cytarabine; Etoposide; Melphalan; Peripheral Blood Stem Cell Transplantation; ibritumomab tiuxetan

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Jane N. Winter, MD

  Robert H. Lurie Cancer Center

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: April 7, 2003
• First Posted: April 9, 2003
• Study Start: April 1, 2000
• Primary Completion: June 1, 2006
• Study Completion: March 1, 2009
• Last Updated: June 1, 2012

Record last verified: 2012-05

Locations

US (3)