NCT01044745

Brief Summary

This phase II trial is studying how well rituximab works in preventing acute graft-versus-host disease (GVHD) in patients undergoing a donor stem cell transplant for hematologic cancer. Giving chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving a monoclonal antibody, rituximab, together with anti-thymocyte globulin, tacrolimus, and mycophenolate mofetil before and after the transplant may stop this from happening

Trial Health

57
Monitor

Trial Health Score

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

Enrollment
20

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Dec 2009

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

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

December 10, 2009

Completed
28 days until next milestone

First Submitted

Initial submission to the registry

January 7, 2010

Completed
1 day until next milestone

First Posted

Study publicly available on registry

January 8, 2010

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 19, 2012

Completed
4.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 10, 2017

Completed
1.4 years until next milestone

Results Posted

Study results publicly available

February 26, 2019

Completed
Last Updated

September 6, 2023

Status Verified

August 1, 2023

Enrollment Period

3 years

First QC Date

January 7, 2010

Results QC Date

January 23, 2018

Last Update Submit

August 23, 2023

Conditions

Accelerated Phase Chronic Myelogenous LeukemiaAdult Acute Lymphoblastic Leukemia in RemissionAdult Acute Myeloid Leukemia in RemissionAdult Nasal Type Extranodal NK/T-cell LymphomaBlastic Phase Chronic Myelogenous LeukemiaContiguous Stage II Adult Burkitt LymphomaContiguous Stage II Adult Diffuse Large Cell LymphomaContiguous Stage II Adult Diffuse Mixed Cell LymphomaContiguous Stage II Adult Diffuse Small Cleaved Cell LymphomaContiguous Stage II Adult Immunoblastic Large Cell LymphomaContiguous Stage II Adult Lymphoblastic LymphomaContiguous Stage II Grade 1 Follicular LymphomaContiguous Stage II Grade 2 Follicular LymphomaContiguous Stage II Grade 3 Follicular LymphomaContiguous Stage II Mantle Cell LymphomaContiguous Stage II Marginal Zone LymphomaContiguous Stage II Small Lymphocytic Lymphomade Novo Myelodysplastic SyndromesExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissueGraft Versus Host DiseaseNodal Marginal Zone B-cell LymphomaNoncontiguous Stage II Adult Burkitt LymphomaNoncontiguous Stage II Adult Diffuse Large Cell LymphomaNoncontiguous Stage II Adult Diffuse Mixed Cell LymphomaNoncontiguous Stage II Adult Diffuse Small Cleaved Cell LymphomaNoncontiguous Stage II Adult Immunoblastic Large Cell LymphomaNoncontiguous Stage II Adult Lymphoblastic LymphomaNoncontiguous Stage II Grade 1 Follicular LymphomaNoncontiguous Stage II Grade 2 Follicular LymphomaNoncontiguous Stage II Grade 3 Follicular LymphomaNoncontiguous Stage II Mantle Cell LymphomaNoncontiguous Stage II Marginal Zone LymphomaNoncontiguous Stage II Small Lymphocytic LymphomaPreviously Treated Myelodysplastic SyndromesRecurrent Adult Acute Lymphoblastic LeukemiaRecurrent Adult Acute Myeloid LeukemiaRecurrent Adult Burkitt LymphomaRecurrent Adult Diffuse Large Cell LymphomaRecurrent Adult Diffuse Mixed Cell LymphomaRecurrent Adult Diffuse Small Cleaved Cell LymphomaRecurrent Adult Grade III Lymphomatoid GranulomatosisRecurrent Adult Immunoblastic Large Cell LymphomaRecurrent Adult Lymphoblastic LymphomaRecurrent Adult T-cell Leukemia/LymphomaRecurrent Cutaneous T-cell Non-Hodgkin LymphomaRecurrent Grade 1 Follicular LymphomaRecurrent Grade 2 Follicular LymphomaRecurrent Grade 3 Follicular LymphomaRecurrent Mantle Cell LymphomaRecurrent Marginal Zone LymphomaRecurrent Mycosis Fungoides/Sezary SyndromeRecurrent Small Lymphocytic LymphomaRefractory Chronic Lymphocytic LeukemiaRelapsing Chronic Myelogenous LeukemiaSecondary Myelodysplastic SyndromesSplenic Marginal Zone LymphomaStage I Adult Burkitt LymphomaStage I Adult Diffuse Large Cell LymphomaStage I Adult Diffuse Mixed Cell LymphomaStage I Adult Diffuse Small Cleaved Cell LymphomaStage I Adult Immunoblastic Large Cell LymphomaStage I Adult Lymphoblastic LymphomaStage I Adult T-cell Leukemia/LymphomaStage I Chronic Lymphocytic LeukemiaStage I Cutaneous T-cell Non-Hodgkin LymphomaStage I Grade 1 Follicular LymphomaStage I Grade 2 Follicular LymphomaStage I Grade 3 Follicular LymphomaStage I Mantle Cell LymphomaStage I Marginal Zone LymphomaStage I Mycosis Fungoides/Sezary SyndromeStage I Small Lymphocytic LymphomaStage II Adult T-cell Leukemia/LymphomaStage II Chronic Lymphocytic LeukemiaStage II Cutaneous T-cell Non-Hodgkin LymphomaStage II Mycosis Fungoides/Sezary SyndromeStage III Adult Burkitt LymphomaStage III Adult Diffuse Large Cell LymphomaStage III Adult Diffuse Mixed Cell LymphomaStage III Adult Diffuse Small Cleaved Cell LymphomaStage III Adult Immunoblastic Large Cell LymphomaStage III Adult Lymphoblastic LymphomaStage III Adult T-cell Leukemia/LymphomaStage III Chronic Lymphocytic LeukemiaStage III Cutaneous T-cell Non-Hodgkin LymphomaStage III Grade 1 Follicular LymphomaStage III Grade 2 Follicular LymphomaStage III Grade 3 Follicular LymphomaStage III Mantle Cell LymphomaStage III Marginal Zone LymphomaStage III Mycosis Fungoides/Sezary SyndromeStage III Small Lymphocytic LymphomaStage IV Adult Burkitt LymphomaStage IV Adult Diffuse Large Cell LymphomaStage IV Adult Diffuse Mixed Cell LymphomaStage IV Adult Diffuse Small Cleaved Cell LymphomaStage IV Adult Immunoblastic Large Cell LymphomaStage IV Adult Lymphoblastic LymphomaStage IV Adult T-cell Leukemia/LymphomaStage IV Chronic Lymphocytic LeukemiaStage IV Cutaneous T-cell Non-Hodgkin LymphomaStage IV Grade 1 Follicular LymphomaStage IV Grade 2 Follicular LymphomaStage IV Grade 3 Follicular LymphomaStage IV Mantle Cell LymphomaStage IV Marginal Zone LymphomaStage IV Mycosis Fungoides/Sezary SyndromeStage IV Small Lymphocytic LymphomaUntreated Adult Acute Lymphoblastic LeukemiaUntreated Adult Acute Myeloid LeukemiaWaldenström Macroglobulinemia

Outcome Measures

Primary Outcomes (1)

  • Number of Participants With Grades II-IV Acute GVHD

    Determined with death as a competing risk. Defined and staged using the 1994 consensus conference modifications of the Glucksberg criteria.

    At day 100

Secondary Outcomes (3)

  • Event-free Survival

    From the date of transplant with relapse/progression or death as censored events, up to 2 years

  • Overall Survival

    From the date of transplant with death from any cause as a censored event, up to 2 years

  • Transplant-related Mortality (TRM)

    At day 100

Study Arms (1)

Treatment (Rituximab and allogeneic HCT transplant)

EXPERIMENTAL

CONDITIONING REGIMEN: Patients receive one of the following conditioning regimens as per the transplant physician: cyclophosphamide and TBI; targeted busulfan and fludarabine; reduced-dose busulfan and fludarabine; or fludarabine and TBI. GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS: Patients receive rituximab IV on days -6, 1, 8, and 15 and anti-thymocyte globulin IV over 6-8 hours on days -3 to -1. Patients also receive tacrolimus IV continuously and then PO beginning on day -1 and continuing until day 150 followed by a taper until day 180 and mycophenolate mofetil PO or IV twice daily on days -1 to 60. TRANSPLANTATION: Patients undergo allogeneic hematopoietic stem cell transplantation on day 0.

Drug: rituximabDrug: mycophenolate mofetilDrug: tacrolimusDrug: anti-thymocyte globulinProcedure: allogeneic hematopoietic stem cell transplantationOther: laboratory biomarker analysisBiological: graft versus host disease prophylaxis/therapyDrug: cyclophosphamideDrug: fludarabine phosphateDrug: busulfanRadiation: total-body irradiationBiological: graft-versus-tumor induction therapyBiological: immunosuppressive therapy

Interventions

Given IV

Also known as: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan
Treatment (Rituximab and allogeneic HCT transplant)

Given IV or PO

Also known as: Cellcept, MMF
Treatment (Rituximab and allogeneic HCT transplant)

Given IV

Also known as: FK 506, Prograf
Treatment (Rituximab and allogeneic HCT transplant)

Given IV

Also known as: ATG, ATGAM, lymphocyte immune globulin, Thymoglobulin
Treatment (Rituximab and allogeneic HCT transplant)

Stem cell transplant

Treatment (Rituximab and allogeneic HCT transplant)

Correlative studies

Treatment (Rituximab and allogeneic HCT transplant)

Undergo graft versus host disease prophylaxis/therapy

Also known as: prophylaxis/therapy, graft versus host disease, prophylaxis/therapy, GVHD
Treatment (Rituximab and allogeneic HCT transplant)

Given PO or IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana
Treatment (Rituximab and allogeneic HCT transplant)

Given IV

Also known as: 2-F-ara-AMP, Beneflur, Fludara
Treatment (Rituximab and allogeneic HCT transplant)

Given IV

Also known as: BSF, BU, Misulfan, Mitosan, Myeloleukon
Treatment (Rituximab and allogeneic HCT transplant)

Undergo TBI

Also known as: TBI
Treatment (Rituximab and allogeneic HCT transplant)

Undergo graft-versus-tumor induction therapy

Also known as: graft versus host disease induction, graft versus tumor induction
Treatment (Rituximab and allogeneic HCT transplant)

Undergo immunosuppressive therapy

Also known as: immunosuppression
Treatment (Rituximab and allogeneic HCT transplant)

Eligibility Criteria

Age19 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Diagnosis of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML) in accelerated phase or blast crisis, chronic lymphocytic leukemia (CLL), Non-Hodgkin lymphoma (NHL), myelodysplastic syndromes (MDS) (intermediate-2 or high-risk disease by International Pelvic Pain Society \[IPPS\])
  • Patients with AML, ALL, or MDS scheduled for myeloablative conditioning should have =\< 10% blasts in bone marrow or peripheral blood at the start of conditioning
  • Patients with AML, ALL, or CML scheduled for reduced intensity conditioning or non-myeloablative conditioning should be in complete morphologic remission at the start of conditioning (residual disease by flow cytometry or cytogenetics and/or incomplete recovery of neutrophil or platelet count are acceptable)
  • Patients with CLL or NHL scheduled for reduced intensity or non-myeloablative conditioning should have no evidence of bulky disease (\> 50% bone marrow involvement or masses \> 10 cm) at the start of conditioning
  • Fulfills all pulmonary, cardiac, renal, and hepatic criteria for standard-of-care matched unrelated donor (MUD) allogeneic HCT
  • Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for twelve months after stem cell transplantation
  • Adequately matched unrelated donor available
  • Written informed consent; written informed consent of the unrelated donor is required to participate in the optional studies

You may not qualify if:

  • Patient or donor infected with human immunodeficiency virus (HIV)
  • Patient or donor with history of hepatitis B or C and/or positive serology consistent with previous hepatitis B or C infection (patients and/or donor who received Hepatitis B vaccination are acceptable)
  • Patient or donor with active hepatitis B or C and/or detectable viral ribonucleic acid (RNA)
  • More than 20,000 circulating CD20+ cells/uL
  • Treatment with rituximab for any reason in the 12 months preceding HCT
  • Patient scheduled for cord blood transplantation
  • Presence of active uncontrolled infection at start of conditioning
  • Presence of active central nervous system (CNS) disease (history of adequately treated CNS disease is acceptable)
  • Presence of uncontrolled psychiatric disorder
  • Patient unable to give informed consent
  • Unrelated donor products received from the Deutsche Knochenmarkspenderdatei (DKMS) Registry are not eligible for the optional study

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Accelerated PhaseLymphoma, Extranodal NK-T-CellBlast CrisisGraft vs Host DiseaseLymphoma, B-Cell, Marginal ZonePrecursor Cell Lymphoblastic Leukemia-LymphomaLeukemia, Myeloid, AcuteBurkitt LymphomaLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinLymphoma, Large-Cell, ImmunoblasticPrecursor T-Cell Lymphoblastic Leukemia-LymphomaLymphoma, T-Cell, CutaneousLymphoma, FollicularLymphoma, Mantle-CellMycosis FungoidesSezary SyndromeLeukemia, Lymphocytic, Chronic, B-CellWaldenstrom Macroglobulinemia

Interventions

RituximabMycophenolic AcidTacrolimusAntilymphocyte SerumthymoglobulinTherapeuticsCyclophosphamidefludarabine phosphateBusulfanWhole-Body IrradiationImmunosuppression Therapy

Condition Hierarchy (Ancestors)

Leukemia, Myelogenous, Chronic, BCR-ABL PositiveLeukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsMyeloproliferative DisordersBone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLymphoma, T-CellLymphomaCell Transformation, NeoplasticCarcinogenesisNeoplastic ProcessesImmune System DiseasesLymphoma, B-CellLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersLeukemia, LymphoidEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLeukemia, B-CellNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsCaproatesAcids, AcyclicCarboxylic AcidsOrganic ChemicalsFatty AcidsLipidsMacrolidesLactonesImmune SeraBiological ProductsComplex MixturesPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsPhosphoramidesOrganophosphorus CompoundsButylene GlycolsGlycolsAlcoholsMesylatesAlkanesulfonatesAlkanesulfonic AcidsAlkanesHydrocarbons, AcyclicSulfonic AcidsSulfur AcidsSulfur CompoundsRadiotherapyInvestigative TechniquesImmunotherapyImmunomodulationBiological TherapyImmunologic Techniques

Results Point of Contact

Title
R. Gregory Bociek, MD
Organization
University of Nebraska Medical Center

Study Officials

  • Robert Bociek, MD

    University of Nebraska

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 7, 2010

First Posted

January 8, 2010

Study Start

December 10, 2009

Primary Completion

December 19, 2012

Study Completion

October 10, 2017

Last Updated

September 6, 2023

Results First Posted

February 26, 2019

Record last verified: 2023-08

Locations