NCT02366663

Brief Summary

This randomized phase III trial studies 90-yttrium ibritumomab tiuxetan and combination chemotherapy compared with combination chemotherapy alone before stem cell transplant in treating patients with diffuse large b-cell non-Hodgkin lymphoma that has returned after a period of improvement. Radioactive substances linked to monoclonal antibodies, such as 90-yttrium ibritumomab tiuxetan, can bind to cancer cells and give off radiation which may help kill cancer cells. Drugs used in chemotherapy, such as carmustine, etoposide phosphate, cytarabine, and melphalan (BEAM), work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether 90-yttrium ibritumomab tiuxetan and BEAM before a stem cell transplant are more effective than BEAM alone in treating patients with diffuse large b-cell non-Hodgkin lymphoma.

Trial Health

57
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Trial Health Score

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

Enrollment
3

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Jan 2015

Geographic Reach
1 country

2 active sites

Status
terminated

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, 2015

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

February 9, 2015

Completed
10 days until next milestone

First Posted

Study publicly available on registry

February 19, 2015

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2016

Completed
1.4 years until next milestone

Results Posted

Study results publicly available

February 13, 2018

Completed
Last Updated

March 12, 2018

Status Verified

February 1, 2018

Enrollment Period

1.8 years

First QC Date

February 9, 2015

Results QC Date

October 4, 2017

Last Update Submit

February 12, 2018

Conditions

Recurrent Diffuse Large B-Cell LymphomaRefractory Diffuse Large B-Cell Lymphoma

Keywords

Non-Hodgkin's lymphomaautologous stem cell transplantationradioimmunotherapyZevalinLymphomaLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinImmune System DiseasesImmunoproliferative DisordersLymphatic DiseasesLymphoma, B-CellLymphoproliferative DisordersNeoplasmsNeoplasms by Histologic TypeAntibodies, MonoclonalImmunologic FactorsPharmacologic ActionsPhysiological Effects of Drugs

Outcome Measures

Primary Outcomes (1)

  • Overall Survival

    Survival estimates will be calculated using the Kaplan-Meier method

    Measured from randomization to date of death or last follow up date, whichever occurs first, for up to 5 years post randomization

Secondary Outcomes (10)

  • Progression-free Survival

    Measured from randomization until death, relapse/progression, receipt of anti-lymphoma therapy, or last follow up whichever comes first, for up to 5 years post randomization

  • Time to Progression

    Up to 5 years

  • Number of Patients With Complete or Partial Response at Day 30

    Day 0 to Day +30 post-HCT

  • Time to Neutrophil Engraftment

    Day 0 to Day 100 post-HCT

  • Incidence of Infection

    Day 0 to Day +100 post-HCT

  • +5 more secondary outcomes

Study Arms (2)

Arm I (ZBEAM)

EXPERIMENTAL

Patients receive rituximab IV on days -21 and -14, and 90-yttrium ibritumomab tiuxetan IV on day -14. Patients also receive BEAM comprising carmustine IV over 4 hours on day -6; cytarabine IV over 2 hours BID on days -5 to -2; etoposide IV over 1 hour BID or QD on days -5 to -2; and melphalan IV on day -1. Patients then undergo autologous hematopoietic stem cell transplant on day 0.

Radiation: 90-Yttrium Ibritumomab tiuxetanDrug: CarmustineDrug: EtoposideDrug: CytarabineDrug: MelphalanProcedure: Autologous Hematopoietic Stem Cell TransplantBiological: Rituximab

Arm II (BEAM)

ACTIVE COMPARATOR

Patients receive BEAM comprising carmustine IV over 4 hours on day -6; cytarabine IV over 2 hours BID on days -5 to -2; etoposide IV over 1 hour BID or QD on days -5 to -2; and melphalan IV on day -1. Patients then undergo autologous hematopoietic stem cell transplant on day 0.

Drug: CarmustineDrug: EtoposideDrug: CytarabineDrug: MelphalanProcedure: Autologous Hematopoietic Stem Cell Transplant

Interventions

90-Yttrium Ibritumomab tiuxetanRADIATION

0.4 mCi/kg given IV

Also known as: IDEC Y2B8, Zevalin
Arm I (ZBEAM)
CarmustineDRUG

Given IV

Also known as: BiCNU, FDA 0345
Arm I (ZBEAM)Arm II (BEAM)
EtoposideDRUG

Given IV

Also known as: VP-16, Lastet
Arm I (ZBEAM)Arm II (BEAM)
CytarabineDRUG

Given IV

Also known as: Cytosar-U, CHX-3311, U-19920
Arm I (ZBEAM)Arm II (BEAM)
MelphalanDRUG

Given IV

Also known as: Alkeran
Arm I (ZBEAM)Arm II (BEAM)
Autologous Hematopoietic Stem Cell TransplantPROCEDURE

Autologous Hematopoietic Stem Cell Transplantation (ASCT)

Also known as: Autologous Stem Cell Transplant
Arm I (ZBEAM)Arm II (BEAM)
RituximabBIOLOGICAL

Given IV

Also known as: MOAB IDEC-C2B8
Arm I (ZBEAM)

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with CD20 positive diffuse large B-cell lymphoma as confirmed by a pathological biopsy report.
  • Patients who are candidates for autologous stem-cell transplantation due to primary refractory or first relapse of disease.
  • Patients must have chemo-sensitive disease achieving at least partial response (Cheson 2007 criteria) to last chemotherapy.
  • Patients with adequate autologous stem cell collection for transplantation (target \>= 2.5 x 10\^6 CD34+ cells/kg).
  • Patients must sign written informed consent.
  • Adequate birth control in fertile patients.
  • All prior chemotherapy completed at least three weeks before study treatment.
  • Marrow involvement less than 25% at transplantation, no limitation on blood counts (low platelet count allowed).
  • Negative HIV antibody.

You may not qualify if:

  • Chemo-refractory disease as determined by less than partial response (Cheson 2007 Criteria) to last chemotherapy.
  • Two or more relapses after initial response to induction chemotherapy.
  • High-grade transformation from earlier diagnosis of low-grade lymphoma. Patients with "De Novo" Transformed DLBCL, defined as DLBCL only on lymph node biopsy and a discordant marrow with para-trabecular small cells at first diagnosis of lymphoma, are eligible if adherent to all other selection criteria.
  • Bilirubin \> 3.0 mg/dl, transaminases \> 3 times upper normal limit.
  • Creatinine \> 2.0 mg/dl.
  • KPS \< 70.
  • Uncontrolled infection.
  • Pregnancy or lactation.
  • Abnormal lung diffusion capacity (DLCO \< 40% predicted).
  • Severe cardiovascular disease; New York Heart Association (NYHA) Functional Classification ≥2.
  • Active CNS disease involvement.
  • Pleural effusion or ascites \> 1 liter.
  • Known hypersensitivity to rituximab.
  • Psychiatric conditions/disease that impair the ability to give informed consent or to adequately co-operate.
  • Prior radioimmunotherapy.
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinLymphomaImmune System DiseasesImmunoproliferative DisordersLymphatic DiseasesLymphoma, B-CellLymphoproliferative DisordersNeoplasmsNeoplasms by Histologic Type

Interventions

ibritumomab tiuxetanCarmustineEtoposideCytarabineMelphalanRituximab

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Nitrosourea CompoundsUreaAmidesOrganic ChemicalsNitroso CompoundsPodophyllotoxinTetrahydronaphthalenesNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsPolycyclic CompoundsGlucosidesGlycosidesCarbohydratesCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsArabinonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedPhenylalanineAmino Acids, AromaticAmino Acids, CyclicAmino AcidsAmino Acids, Peptides, and ProteinsAntibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsSerum GlobulinsGlobulins

Results Point of Contact

Title
Dr. Amrita Krishnan
Organization
City of Hope National Medical Center
AKrishnan@coh.org
626-256-4673

Study Officials

  • Amrita Y. Krishnan MD, MD

    City of Hope Medical Center

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 9, 2015

First Posted

February 19, 2015

Study Start

January 1, 2015

Primary Completion

October 1, 2016

Study Completion

October 1, 2016

Last Updated

March 12, 2018

Results First Posted

February 13, 2018

Record last verified: 2018-02

Locations

US(2)