Iodine I 131 Tositumomab and Fludarabine Phosphate in Treating Older Patients Who Are Undergoing an Autologous or Syngeneic Stem Cell Transplant for Relapsed or Refractory Non-Hodgkin's Lymphoma

NCT ID: NCT00110071

Last Updated: 2014-08-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-01-31

Brief Summary

This phase I trial studies the side effects and best dose of fludarabine (fludarabine phosphate) when given together with iodine I 131 tositumomab in treating older patients who are undergoing an autologous or syngeneic stem cell transplant for relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). Radiolabeled monoclonal antibodies, such as iodine I 131 tositumomab, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy. Giving iodine I 131 tositumomab together with fludarabine followed by autologous stem cell transplant may be an effective treatment for NHL

Detailed Description

PRIMARY OBJECTIVES:

I. To estimate the maximally tolerated dose of fludarabine that can be combined with 131I-anti-CD20 (iodine I 131 tositumomab) delivering =< 27Gy to critical normal organs followed by autologous or syngeneic transplantation in patients >= 60 years of age with relapsed B-NHL.

SECONDARY OBJECTIVES:

I. To assess the overall and progression-free survival of the above regimen in such patients.

II. To evaluate the response rates of the above therapy.

III. To evaluate the toxicity and tolerability of the above therapy.

IV. To evaluate the feasibility of delivering concurrent high-dose radioimmunotherapy (RIT) and chemotherapy.

OUTLINE: This is a dose-escalation study of fludarabine phosphate as used in combination with I 131 tositumomab and stem cell transplant.

Patients receive a dosimetric dose of iodine I 131 tositumomab intravenously (IV) over 40-60 minutes on day -24 followed by gamma camera imaging over the next 6 days. Patients then receive a therapeutic dose of iodine I 131 tositumomab via central line over 40-60 minutes on day -14. Patients also receive fludarabine phosphate IV once daily (QD) on days -11 to -9 OR days -11 or -7. Patients undergo autologous or syngeneic peripheral blood stem cell transplantation on day 0.

Patients with circulating lymphoma cells by peripheral smear receive tositumomab IV over 1 hour OR rituximab IV over 1 hour followed by tositumomab IV over 1 hour before the dosimetric iodine I 131 tositumomab infusion.

After completion of study treatment, patients are followed up at 1, 3, 6, and 12 months and then annually thereafter.

Conditions

Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (chemoradioimmunotherapy)

Patients receive a dosimetric dose of iodine I 131 tositumomab IV over 40-60 minutes on day -24 followed by gamma camera imaging over the next 6 days. Patients then receive a therapeutic dose of iodine I 131 tositumomab via central line over 40-60 minutes on day -14. Patients also receive fludarabine phosphate IV QD on days -11 to -9 OR days -11 or -7. Patients undergo autologous or syngeneic peripheral blood stem cell transplantation on day 0.

Group Type: EXPERIMENTAL

fludarabine phosphate

Intervention Type: DRUG

Given IV

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Undergo transplantation (infusion of autologous or syngeneic PBSC via central line)

iodine I 131 tositumomab

Intervention Type: RADIATION

Given IV (dosimetric dose) or via central line (therapeutic dose)

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

flow cytometry

Intervention Type: OTHER

Correlative studies

polymerase chain reaction

Intervention Type: GENETIC

Correlative studies

Interventions

fludarabine phosphate

Given IV

Intervention Type: DRUG

peripheral blood stem cell transplantation

Undergo transplantation (infusion of autologous or syngeneic PBSC via central line)

Intervention Type: PROCEDURE

iodine I 131 tositumomab

Given IV (dosimetric dose) or via central line (therapeutic dose)

Intervention Type: RADIATION

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

flow cytometry

Correlative studies

Intervention Type: OTHER

polymerase chain reaction

Correlative studies

Intervention Type: GENETIC

Other Intervention Names

2-F-ara-AMP; Beneflur; Fludara; PBPC transplantation; PBSC transplantation; peripheral blood progenitor cell transplantation; transplantation, peripheral blood stem cell; 131-I-anti-B1 antibody; 131-I-anti-B1 monoclonal antibody; I131-MOAB-B1; iodine I 131 MOAB anti-B1; iodine I 131 monoclonal antibody anti-B1; PCR

Eligibility Criteria

Inclusion Criteria

• Patients must have a histologically confirmed diagnosis of lymphoma expressing the CD20 antigen and generally must have failed at least one prior standard systemic therapy; the exception will be mantle cell lymphoma (MCL) patients, who may be enrolled while in first complete remission (CR) in accordance with current transplant standard of care for these patients
• Creatinine (Cr) < 2.0
• Bilirubin < 1.5 mg/dL, with the exception of patients thought to have Gilbert's syndrome, whom may have a total bilirubin above 1.5 mg/dL
• All patients eligible for therapeutic study must have (>= 2x10^6 CD34/kg) autologous hematopoietic stem cells harvested and cryopreserved, or this number of cells harvested from a syngeneic donor
• Patients must have an expected survival of > 60 days and must be free of major infection
• DONOR: Syngeneic donors must be confirmed syngeneic by ABO typing, human leukocyte antigen (HLA) typing, and variable number tandem repeat (VNTR) analysis
• DONOR: Syngeneic donors must meet eligibility under Standard Practice Guidelines/Standard Treatment

Exclusion Criteria

• Circulating anti-mouse antibody (HAMA) (to be determined before both dosimetry and therapy)
• Systemic anti-lymphoma therapy given in the previous 30 days before the scheduled therapy dose
• Inability to understand or give an informed consent
• Prior radiation > 20 Gy to any critical normal organ (e.g., lung, liver, spinal cord, > 25% of red marrow)
• Central nervous system lymphoma
• Other serious medical conditions considered to represent contraindications to bone marrow transplant (BMT) (e.g., abnormally decreased cardiac ejection fraction, diffusing capacity (DLCO) < 50% predicted, patient on supplemental oxygen, acquired Immunodeficiency syndrome [AIDS], etc.)
• Pregnancy
• Prior bone marrow or stem cell transplant
• South West Oncology Group (SWOG) performance status >= 2
• Unable to perform self-care during radiation isolation
• Patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma/well differentiated lymphocytic lymphoma

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ajay Gopal

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Locations

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, United States

Countries

United States

References

Gopal AK, Gooley TA, Rajendran JG, Pagel JM, Fisher DR, Maloney DG, Appelbaum FR, Cassaday RD, Shields A, Press OW. Myeloablative I-131-tositumomab with escalating doses of fludarabine and autologous hematopoietic transplantation for adults age >/= 60 years with B cell lymphoma. Biol Blood Marrow Transplant. 2014 Jun;20(6):770-5. doi: 10.1016/j.bbmt.2014.02.004. Epub 2014 Feb 12.

Reference Type: DERIVED

PMID: 24530971 (View on PubMed)

Other Identifiers

NCI-2009-01470

Identifier Type: REGISTRY

Identifier Source: secondary_id

P01CA044991

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1943.00

Identifier Type: -

Identifier Source: org_study_id