NCT00691015

Brief Summary

RATIONALE: Giving low doses of chemotherapy, monoclonal antibodies, and radiation therapy before a donor peripheral blood 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 tacrolimus, sirolimus, and antithymocyte globulin before and after transplant may stop this from happening. PURPOSE: This phase II trial is studying the side effects of giving sirolimus together with tacrolimus and antithymocyte globulin and to see how well it works in preventing graft-versus-host disease in patients with hematologic cancer who are undergoing donor stem cell transplant.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
48

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started May 2008

Longer than P75 for phase_2

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

May 1, 2008

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

June 4, 2008

Completed
1 day until next milestone

First Posted

Study publicly available on registry

June 5, 2008

Completed
5.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2014

Completed
3.2 years until next milestone

Results Posted

Study results publicly available

June 28, 2017

Completed
Last Updated

June 28, 2017

Status Verified

May 1, 2017

Enrollment Period

5.9 years

First QC Date

June 4, 2008

Results QC Date

December 9, 2015

Last Update Submit

May 26, 2017

Conditions

Keywords

stage 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 Hodgkin lymphomastage III adult immunoblastic large cell lymphomastage III adult lymphoblastic 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 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 Hodgkin lymphomastage IV adult immunoblastic large cell lymphomastage IV adult lymphoblastic 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 small lymphocytic lymphomaextranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissuenodal marginal zone B-cell lymphomasplenic marginal zone 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 lymphomaaccelerated phase chronic myelogenous leukemiaadult acute lymphoblastic leukemia in remissionadult acute myeloid leukemia in remissionadult acute myeloid leukemia with 11q23 (MLL) abnormalitiesadult acute myeloid leukemia with inv(16)(p13;q22)adult acute myeloid leukemia with t(15;17)(q22;q12)adult acute myeloid leukemia with t(16;16)(p13;q22)adult acute myeloid leukemia with t(8;21)(q22;q22)chronic phase chronic myelogenous leukemiarecurrent adult acute lymphoblastic leukemiarecurrent adult acute myeloid leukemiasecondary acute myeloid leukemiastage III chronic lymphocytic leukemiastage IV chronic lymphocytic leukemiade novo myelodysplastic syndromesmyelodysplastic/myeloproliferative neoplasm, unclassifiablepreviously treated myelodysplastic syndromessecondary myelodysplastic syndromesstage I multiple myelomastage II multiple myelomastage III multiple myelomaprimary myelofibrosisatypical chronic myeloid leukemia, BCR-ABL negativechronic eosinophilic leukemiachronic myelomonocytic leukemiachronic neutrophilic leukemia

Outcome Measures

Primary Outcomes (3)

  • Incidence of Acute Graft-versus-host Disease (GVHD)

    Within 100 days after donor peripheral blood stem cell transplantation (PBSCT) as assessed by Glucksberg criteria

  • Severity of Acute Graft-versus-host Disease (GVHD)

    Within 100 days after donor peripheral blood stem cell transplantation (PBSCT) as assessed by Glucksberg criteria

  • Safety, as Defined by Serious Adverse Events and Adverse Events Related to Study Treatment.

    Within 6 months after PBSCT

Secondary Outcomes (5)

  • Incidence of Chronic GVHD.

    Within 2 years after PBSCT

  • Time to Engraftment (i.e., Absolute Neutrophil Recovery [ANC > 500/mm³] )

    post transplant, up to 4 weeks

  • Overall Survival.

    At 2 years after PBSCT

  • Incidence of Infections, Including Bacterial, Fungal, and Viral Infections (i.e., CMV and EBV Reactivation, Including Post-transplant Lymphoproliferative Disorders)

    Within 6 months after PBSCT

  • Karnofsky Performance Status Performance Status

    At 90 days after PBSCT

Study Arms (1)

Chemotherapy or chemotherapy + total body irradiation

EXPERIMENTAL

Standard of care (SOC) chemotherapy or ( SOC) chemotherapy + total body irradiation (TBI) of one of the following regimens: Regimen I: Patients receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV. Regimen II: Patients undergo total body irradiation (TBI) twice daily for 8 fractions and receive etoposide IV;anti-thymocyte globulin IV. Regimen III: Patients undergo TBI once or twice daily for 11 fractions and receive cyclophosphamide IV; anti-thymocyte globulin IV. Regimen IV: Patients undergo TBI and receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV. Regimen V: Patients receive carmustine IV, etoposide IV, cytarabine IV, and melphalan IV. Some patients also receive rituximab IV; anti-thymocyte globulin IV. Regimen VI: Patients receive fludarabine phosphate IV and melphalan IV. Some patients also undergo TBI; anti-thymocyte globulin IV.

Biological: rituximabDrug: busulfanDrug: carmustineDrug: cyclophosphamideDrug: cytarabineDrug: etoposideDrug: fludarabine phosphateDrug: melphalanRadiation: total body irradiation (TBI)Drug: anti-thymocyte globulin IV

Interventions

rituximabBIOLOGICAL

Given IV

Also known as: Rituxan, MabThera, Zytux
Chemotherapy or chemotherapy + total body irradiation

Given IV

Also known as: Busulfex, Myleran
Chemotherapy or chemotherapy + total body irradiation

Given IV

Also known as: Bicnu, Gliadel
Chemotherapy or chemotherapy + total body irradiation

Given IV

Also known as: Cytoxan, Cytoxan Lyophilized, Neosar
Chemotherapy or chemotherapy + total body irradiation

Given IV

Also known as: Depocyt
Chemotherapy or chemotherapy + total body irradiation

Given IV

Also known as: Etopophos, Toposar
Chemotherapy or chemotherapy + total body irradiation

Given IV

Also known as: Fludara®
Chemotherapy or chemotherapy + total body irradiation

Given IV

Also known as: Alkeran
Chemotherapy or chemotherapy + total body irradiation

Given once or twice daily

Also known as: radiotherapy
Chemotherapy or chemotherapy + total body irradiation

Given IV

Also known as: Thymoglobulin
Chemotherapy or chemotherapy + total body irradiation

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
DISEASE CHARACTERISTICS: * Diagnosis of a hematological malignancy, including any of the following: * Non-Hodgkin lymphoma in complete remission (CR) or partial remission (PR) * Hodgkin lymphoma in CR or PR * Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) meeting either of the following criteria: * In CR * Not in CR and meets the following criteria: * Bone marrow blast \< 20% within 4 weeks of transplantation * Peripheral blood absolute blast count \< 500 per microliter on the day of initiating conditioning therapy * Myelodysplastic syndromes, treated or untreated * Chronic myeloid leukemia in chronic phase or accelerated phase * Multiple myeloma in CR or PR * Chronic lymphocytic leukemia in second or greater CR or PR * Myelofibrosis or other myeloproliferative disorders meeting the following criteria: * Bone marrow blasts \< 20% within 4 weeks of transplantation * Peripheral blood absolute blast count \< 500 per microliter on the day of initiating conditioning therapy * Patients with ascites not allowed * No prior bone marrow or ex vivo engineered or processed graft (i.e., CD34+ enrichment, T-cell depletion, etc) * Scheduled to undergo peripheral blood stem cell transplantation from a suitable HLA-matched or -mismatched unrelated donor, as determined by treating physician * High resolution molecular HLA typing is required for HLA class I and II * No more than one antigen or allele mismatch * No documented uncontrolled CNS disease PATIENT CHARACTERISTICS: * ECOG performance status (PS) 0-2 * Karnofsky PS 60-100% * Creatinine clearance \> 50 mL/min * Bilirubin \< 3 times upper limit of normal (ULN) * ALT and AST \< 3 times ULN * LVEF \> 50% * FVC, FEV\_1, or DLCO \> 50% predicted * Patients on home oxygen not allowed * Able to cooperate with oral medication intake * HIV negative * No active hepatitis B or hepatitis C * No known contraindication to sirolimus, tacrolimus, or anti-thymocyte globulin PRIOR CONCURRENT THERAPY: * See Disease Characteristics

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

Sponsors & Collaborators

Study Sites (1)

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201-1379, United States

Location

MeSH Terms

Conditions

Myeloproliferative DisordersLeukemiaLymphomaMultiple MyelomaNeoplasms, Plasma CellMyelodysplastic SyndromesMyelodysplastic-Myeloproliferative DiseasesBurkitt LymphomaLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinHodgkin DiseaseLymphoma, Large-Cell, ImmunoblasticPrecursor Cell Lymphoblastic Leukemia-LymphomaLymphoma, FollicularLymphoma, Mantle-CellLymphoma, B-Cell, Marginal ZoneLeukemia, Lymphocytic, Chronic, B-CellLeukemia, Myeloid, Accelerated PhaseCongenital AbnormalitiesLeukemia, Myeloid, Chronic-PhaseLeukemia, Myeloid, AcutePrimary MyelofibrosisLeukemia, Myeloid, Chronic, Atypical, BCR-ABL NegativePdgfra-Associated Chronic Eosinophilic LeukemiaLeukemia, Myelomonocytic, ChronicLeukemia, Neutrophilic, Chronic

Interventions

RituximabBusulfanCarmustinecarmustine, poliferprosan 20 drug combinationCyclophosphamideCytarabineEtoposideetoposide phosphatefludarabine phosphateMelphalanWhole-Body IrradiationRadiotherapythymoglobulin

Condition Hierarchy (Ancestors)

Bone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLymphoma, B-CellLeukemia, LymphoidLeukemia, B-CellChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLeukemia, Myelogenous, Chronic, BCR-ABL PositiveLeukemia, MyeloidCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsButylene GlycolsGlycolsAlcoholsOrganic ChemicalsMesylatesAlkanesulfonatesAlkanesulfonic AcidsAlkanesHydrocarbons, AcyclicHydrocarbonsSulfonic AcidsSulfur AcidsSulfur CompoundsNitrosourea CompoundsUreaAmidesNitroso CompoundsPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedPhosphoramidesOrganophosphorus CompoundsCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsArabinonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesPodophyllotoxinTetrahydronaphthalenesNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicPolycyclic CompoundsGlucosidesGlycosidesCarbohydratesPhenylalanineAmino Acids, AromaticAmino Acids, CyclicAmino AcidsTherapeuticsInvestigative Techniques

Results Point of Contact

Title
Zaid Al-Kadhimi, M. D.
Organization
Barbara Ann Karmanos Institute

Study Officials

  • Zaid Al-Kadhimi, MD

    Barbara Ann Karmanos Cancer Institute

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
Yes
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
SUPPORTIVE CARE
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

June 4, 2008

First Posted

June 5, 2008

Study Start

May 1, 2008

Primary Completion

April 1, 2014

Study Completion

April 1, 2014

Last Updated

June 28, 2017

Results First Posted

June 28, 2017

Record last verified: 2017-05

Locations