NCT00110071

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

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
38

participants targeted

Target at P50-P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2005

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

May 3, 2005

Completed
1 day until next milestone

First Posted

Study publicly available on registry

May 4, 2005

Completed
6.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2011

Completed
Last Updated

August 6, 2014

Status Verified

August 1, 2014

Enrollment Period

6.4 years

First QC Date

May 3, 2005

Last Update Submit

August 4, 2014

Conditions

Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissueNodal Marginal Zone B-cell LymphomaRecurrent Adult Burkitt LymphomaRecurrent Adult Diffuse Large Cell LymphomaRecurrent Adult Diffuse Mixed Cell LymphomaRecurrent Adult Diffuse Small Cleaved Cell LymphomaRecurrent Adult Immunoblastic Large Cell LymphomaRecurrent Adult Lymphoblastic LymphomaRecurrent Grade 1 Follicular LymphomaRecurrent Grade 2 Follicular LymphomaRecurrent Grade 3 Follicular LymphomaRecurrent Mantle Cell LymphomaRecurrent Marginal Zone LymphomaSplenic Marginal Zone LymphomaWaldenström Macroglobulinemia

Outcome Measures

Primary Outcomes (1)

  • Maximum tolerated dose/dose limiting toxicity

    Assessed according to Bearman scale for Regimen-Related Toxicities.

    Up to 30 days post-transplant

Secondary Outcomes (4)

  • Overall and progression-free survival rate

    Up to 6 years

  • Response rate

    Up to 12 months

  • Toxicity/tolerability of study regimen

    Through day 100 post-transplant

  • Feasibility of concurrent high-dose radioimmunotherapy and chemotherapy

    Through day -7 prior to transplant

Study Arms (1)

Treatment (chemoradioimmunotherapy)

EXPERIMENTAL

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.

Drug: fludarabine phosphateProcedure: peripheral blood stem cell transplantationRadiation: iodine I 131 tositumomabOther: laboratory biomarker analysisOther: flow cytometryGenetic: polymerase chain reaction

Interventions

fludarabine phosphateDRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, Fludara
Treatment (chemoradioimmunotherapy)
peripheral blood stem cell transplantationPROCEDURE

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

Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell
Treatment (chemoradioimmunotherapy)
iodine I 131 tositumomabRADIATION

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

Also known as: 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
Treatment (chemoradioimmunotherapy)
laboratory biomarker analysisOTHER

Correlative studies

Treatment (chemoradioimmunotherapy)
flow cytometryOTHER

Correlative studies

Treatment (chemoradioimmunotherapy)
polymerase chain reactionGENETIC

Correlative studies

Also known as: PCR
Treatment (chemoradioimmunotherapy)

Eligibility Criteria

Age60 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

  • 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.

    PMID: 24530971DERIVED

MeSH Terms

Conditions

Lymphoma, B-Cell, Marginal ZoneBurkitt LymphomaLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinLymphoma, Large-Cell, ImmunoblasticPrecursor Cell Lymphoblastic Leukemia-LymphomaLymphoma, FollicularLymphoma, Mantle-CellWaldenstrom Macroglobulinemia

Interventions

fludarabine phosphatePeripheral Blood Stem Cell Transplantationtositumomab I-131Flow CytometryPolymerase Chain Reaction

Condition Hierarchy (Ancestors)

Lymphoma, B-CellLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLeukemia, LymphoidLeukemiaHematologic DiseasesNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Hematopoietic Stem Cell TransplantationStem Cell TransplantationCell TransplantationCell- and Tissue-Based TherapyBiological TherapyTherapeuticsTransplantationSurgical Procedures, OperativeCell SeparationCytological TechniquesClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisCytophotometryFluorometryLuminescent MeasurementsPhotometryChemistry Techniques, AnalyticalInvestigative TechniquesNucleic Acid Amplification TechniquesGenetic Techniques

Study Officials

  • Ajay Gopal

    Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

First Submitted

May 3, 2005

First Posted

May 4, 2005

Study Start

January 1, 2005

Primary Completion

June 1, 2011

Last Updated

August 6, 2014

Record last verified: 2014-08

Locations

US(1)