NCT00589563

Brief Summary

RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops 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, antithymocyte globulin, and methotrexate before and after transplant may stop this from happening. PURPOSE: This phase II trial is studying how well sirolimus, tacrolimus, and antithymocyte globulin work in preventing graft-versus-host disease in patients undergoing a donor stem cell transplant for hematological cancer .

Trial Health

87
On Track

Trial Health Score

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

Enrollment
32

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started May 2007

Longer than P75 for phase_2

Geographic Reach
1 country

2 active sites

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, 2007

Completed
8 months until next milestone

First Submitted

Initial submission to the registry

December 21, 2007

Completed
19 days until next milestone

First Posted

Study publicly available on registry

January 9, 2008

Completed
4.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2012

Completed
2.5 years until next milestone

Results Posted

Study results publicly available

August 12, 2014

Completed
Last Updated

September 10, 2014

Status Verified

September 1, 2014

Enrollment Period

4.8 years

First QC Date

December 21, 2007

Results QC Date

July 21, 2014

Last Update Submit

September 3, 2014

Conditions

Chronic Myeloproliferative DisordersGraft Versus Host DiseaseInfectionLeukemiaLymphomaMultiple Myeloma and Plasma Cell NeoplasmMyelodysplastic SyndromesMyelodysplastic/Myeloproliferative NeoplasmsPrecancerous ConditionSecondary MyelofibrosisSmall Intestine Cancer

Keywords

graft versus host diseaseinfectionadult favorable prognosis Hodgkin lymphomaadult unfavorable prognosis Hodgkin lymphomachildhood favorable prognosis Hodgkin lymphomachildhood unfavorable prognosis Hodgkin lymphomacutaneous B-cell non-Hodgkin lymphomarecurrent adult Hodgkin lymphomarecurrent cutaneous T-cell non-Hodgkin lymphomarecurrent/refractory childhood Hodgkin lymphomastage I adult Hodgkin lymphomastage I childhood Hodgkin lymphomastage I cutaneous T-cell non-Hodgkin lymphomastage II adult Hodgkin lymphomastage II childhood Hodgkin lymphomastage II cutaneous T-cell non-Hodgkin lymphomastage III adult Hodgkin lymphomastage III childhood Hodgkin lymphomastage III cutaneous T-cell non-Hodgkin lymphomastage IV adult Hodgkin lymphomastage IV childhood Hodgkin lymphomastage IV cutaneous T-cell non-Hodgkin lymphomaanaplastic large cell lymphomaangioimmunoblastic T-cell lymphomaBurkitt lymphomacontiguous 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 lymphomaextranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissuenodal 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 lymphomarecurrent 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 childhood anaplastic large cell lymphomarecurrent childhood grade III lymphomatoid granulomatosisrecurrent childhood lymphoblastic lymphomarecurrent childhood small noncleaved cell lymphomarecurrent grade 1 follicular lymphomarecurrent grade 2 follicular lymphomarecurrent grade 3 follicular lymphomarecurrent grade I lymphomatoid granulomatosisrecurrent grade II lymphomatoid granulomatosisrecurrent mantle cell lymphomarecurrent marginal zone lymphomarecurrent small lymphocytic lymphomasmall intestine lymphomasplenic 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 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 childhood anaplastic large cell lymphomastage III childhood lymphoblastic lymphomastage III childhood small noncleaved cell 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 immunoblastic large cell lymphomastage IV adult lymphoblastic lymphomastage IV adult T-cell leukemia/lymphomastage IV childhood anaplastic large cell lymphomastage IV childhood lymphoblastic lymphomastage IV childhood small noncleaved cell 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 lymphomaadult 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)childhood acute myeloid leukemia in remissionrecurrent adult acute myeloid leukemiarecurrent childhood acute myeloid leukemiasecondary acute myeloid leukemiaadult acute lymphoblastic leukemia in remissionchildhood acute lymphoblastic leukemia in remissionrecurrent adult acute lymphoblastic leukemiarecurrent childhood acute lymphoblastic leukemiaaccelerated phase chronic myelogenous leukemiachronic phase chronic myelogenous leukemiarefractory chronic lymphocytic leukemiarelapsing chronic myelogenous leukemiastage I chronic lymphocytic leukemiastage II chronic lymphocytic leukemiastage III chronic lymphocytic leukemiastage IV chronic lymphocytic leukemiastage I multiple myelomastage II multiple myelomastage III multiple myelomachildhood myelodysplastic syndromesde novo myelodysplastic syndromesmyelodysplastic/myeloproliferative neoplasm, unclassifiablepreviously treated myelodysplastic syndromessecondary myelodysplastic syndromesatypical chronic myeloid leukemia, BCR-ABL negativechronic myelomonocytic leukemiajuvenile myelomonocytic leukemiaprimary myelofibrosissecondary myelofibrosis

Outcome Measures

Primary Outcomes (4)

  • Cumulative Incidence of Grade II-IV Acute Graft-Versus-Host Disease (GVHD) at Day 100

    Patients were evaluated for the development of acute GVHD within the first 100 days post HSCT. The cumulative incidence of grade II-IV acute GVHD was determined using competing risk analysis. Competing risks for acute GVHD were death and nonengraftment.

    100 Days Post Hematopoietic Stem Cell Transplant (HSCT)

  • Severity of Acute GVHD

    All patients were considered for the evaluation of the severity of acute GVHD.

    100 Days Post HSCT

  • Cumulative Incidence of Chronic GVHD

    Patients were evaluated for the development of chronic GVHD from 101 days post HSCT to last contact or documented evidence of the disease. The cumulative incidence of chronic GVHD was determined using competing risk analysis. Competing risks for GVHD were death and nonengraftment.

    2 year point estimate was provided.

  • Severity of Chronic GVHD

    All Patients were considered for the evaluation of chronic GVHD severity.

    Patients were evaluated until they developed chronic GVHD, a median of 130 days post HSCT

Secondary Outcomes (10)

  • Time to Absolute Neutrophil Count Recovery (Engraftment)

    Patients were evaluated until neutrophil recovery, a median of 15 days post HSCT

  • Time to Platelet Count Recovery (Engraftment)

    Patients were evaluated until platelet recovery, a median of 14 days

  • Occurence of Infections Including Cytomegalovirus and Epstein-Barr Virus Reactivation

    Median Follow Up: 28 months (Range: 1-49 months)

  • Occurrence of Thrombotic Microangiopathy

    Median Follow Up: 28 Months (Range: 1-49 months)

  • Occurence of Sinusoidal Obstructive Syndrome (SOS)

    Median Follow Up: 28 Months (Range: 1-49 Months)

  • +5 more secondary outcomes

Study Arms (3)

Fludarabine/Melphalan Conditioning

EXPERIMENTAL

Fludarabine/Melphalan Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis

Biological: anti-thymocyte globulinDrug: fludarabine phosphateDrug: melphalanDrug: methotrexateDrug: sirolimusDrug: tacrolimusProcedure: allogeneic hematopoietic stem cell transplantationProcedure: hematopoietic stem cell transplantationProcedure: nonmyeloablative allogeneic hematopoietic stem cell transplantationProcedure: peripheral blood stem cell transplantationRadiation: total-body irradiation

FTBI/Cytoxan Conditioning

EXPERIMENTAL

FTBI/Cytoxan Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis

Biological: anti-thymocyte globulinDrug: cyclophosphamideDrug: methotrexateDrug: sirolimusDrug: tacrolimusProcedure: allogeneic hematopoietic stem cell transplantationProcedure: hematopoietic stem cell transplantationProcedure: nonmyeloablative allogeneic hematopoietic stem cell transplantationProcedure: peripheral blood stem cell transplantationRadiation: total-body irradiation

FTBI/Etoposide Conditioning

EXPERIMENTAL

FTBI/Etoposide Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis

Biological: anti-thymocyte globulinDrug: etoposideDrug: methotrexateDrug: sirolimusDrug: tacrolimusProcedure: allogeneic hematopoietic stem cell transplantationProcedure: hematopoietic stem cell transplantationProcedure: nonmyeloablative allogeneic hematopoietic stem cell transplantationProcedure: peripheral blood stem cell transplantationRadiation: total-body irradiation

Interventions

anti-thymocyte globulinBIOLOGICAL

0.5 mg/kg on day -3, 1.5 mg/kg on day -2 and 2.5 mg/kg on day -1 or day 0 from stem cell transplant

FTBI/Cytoxan ConditioningFTBI/Etoposide ConditioningFludarabine/Melphalan Conditioning
cyclophosphamideDRUG

60mg/kg on days -5 and -4 from stem cell transplant

FTBI/Cytoxan Conditioning
etoposideDRUG

60mg/kg on day -4 from stem cell transplant

FTBI/Etoposide Conditioning
fludarabine phosphateDRUG

Fludarabine 25 mg/m2/d from days -9 to -5 from stem cell transplant

Fludarabine/Melphalan Conditioning
melphalanDRUG

Melphalan 140 mg/m2 on day -4 from stem cell transplant

Fludarabine/Melphalan Conditioning
methotrexateDRUG

For high risk HLA-mismatch transplant only: 5 mg/m2 on days +1, +3 and +6 from stem cell transplant

FTBI/Cytoxan ConditioningFTBI/Etoposide ConditioningFludarabine/Melphalan Conditioning
sirolimusDRUG

Adults: 12 mg loading dose on day -3 from stem cell transplant followed by 4 mg orally single morning daily dose. Pediatric Patients \<40kg: 3 mg/m2 orally on day -3 from stem cell transplant followed by 1 mg/m2 orally single morning daily dose

FTBI/Cytoxan ConditioningFTBI/Etoposide ConditioningFludarabine/Melphalan Conditioning
tacrolimusDRUG

0.02 mg/kd/d CIV beginning on day -3 from stem cell transplant

FTBI/Cytoxan ConditioningFTBI/Etoposide ConditioningFludarabine/Melphalan Conditioning
allogeneic hematopoietic stem cell transplantationPROCEDURE

The target peripheral blood stem cell dose will be 5-10 x 106/kg actual body weight

FTBI/Cytoxan ConditioningFTBI/Etoposide ConditioningFludarabine/Melphalan Conditioning
hematopoietic stem cell transplantationPROCEDURE

The target peripheral blood stem cell dose will be 5-10 x 106/kg actual body weight

FTBI/Cytoxan ConditioningFTBI/Etoposide ConditioningFludarabine/Melphalan Conditioning
nonmyeloablative allogeneic hematopoietic stem cell transplantationPROCEDURE

Fludarabine 25 mg/m2/d from days -9 to -5 from stem cell transplant, Melphalan 140 mg/m2 on day -4 from stem cell transplant

FTBI/Cytoxan ConditioningFTBI/Etoposide ConditioningFludarabine/Melphalan Conditioning
peripheral blood stem cell transplantationPROCEDURE

The target peripheral blood stem cell dose will be 5-10 x 106/kg actual body weight

FTBI/Cytoxan ConditioningFTBI/Etoposide ConditioningFludarabine/Melphalan Conditioning
total-body irradiationRADIATION

1320 cGy in 11 fractions from day -8 to day -5 or day -9 to day -6 prior to stem cell transplant

FTBI/Cytoxan ConditioningFTBI/Etoposide ConditioningFludarabine/Melphalan Conditioning

Eligibility Criteria

Age2 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
DISEASE CHARACTERISTICS: * Diagnosis of hematological malignancy including any of the following: * Non-Hodgkin lymphoma (NHL) in any complete remission (CR) or partial response (PR) * Hodgkin lymphoma in any CR or PR * Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) in any CR * Bone marrow blasts \< 20% within 4 weeks of transplant and peripheral blood absolute blast count \< 500/µL on the day of initiation of conditioning for patients with non-CR AML or ALL * Myelodysplastic syndromes (MDS) treated or untreated * Chronic myelogenous leukemia (CML) in chronic or accelerated phase * Multiple myeloma in any CR or PR * Chronic lymphocytic leukemia in CR or PR 2 or greater * Myelofibrosis and other myeloproliferative disorders * Bone marrow blasts \< 20% within 4 weeks of transplant and peripheral blood absolute blast count \< 500/µL on the day of initiation * High-risk disease defined as AML or ALL \> CR1, accelerated phase CML, recurrent aggressive lymphoma, or active lymphoproliferative disease at transplant * Low-risk disease defined as AML or ALL in CR1, chronic phase CML, or low-grade lymphoproliferative disorder with controlled disease at transplant * Must be planning to receive 1 of the following conditioning regimens at City of Hope: * Fludarabine phosphate and melphalan for patients with hematological malignancies and contraindications for conventional myeloablative regimens due to age, co-morbidity, or previous transplant * Fractionated total-body irradiation (FTBI) and etoposide for patients with AML and ALL or CML in accelerated phase * FTBI and cyclophosphamide for patients with NHL, AML, CML, and MDS * Suitable unrelated donor available * HLA-matched or mismatched * Peripheral blood stem cells available * No bone marrow or ex vivo-engineered or processed graft (e.g., CD34-positive, T-cell depletion) * No uncontrolled CNS disease PATIENT CHARACTERISTICS: * Karnofsky performance status (PS) 70-100% or ECOG PS 0-2 * Creatinine \< 1.3 mg/dL or creatinine clearance ≥ 70 mL/min * Ejection fraction \> 45% * Direct bilirubin \< 3 times upper limit of normal (ULN) * ALT and AST \< 3 times ULN * Forced vital capacity, FEV1, and DLCO \> 45% of predicted * Able to cooperate with oral medication intake * No active donor or recipient serology positive for HIV * No known contraindication to administration of sirolimus, tacrolimus, or anti-thymocyte globulin * No active hepatitis B or C * Negative pregnancy test PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Concurrent participation in other clinical trials for prevention or treatment of viral, bacterial, or fungal disease allowed provided agents do not interact with agents used in the current study

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

Sponsors & Collaborators

Study Sites (2)

Banner Good Samaritan Medical Center

Phoenix, Arizona, 85006, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010-3000, United States

Location

MeSH Terms

Conditions

Myeloproliferative DisordersGraft vs Host DiseaseInfectionsLeukemiaLymphomaMultiple MyelomaNeoplasms, Plasma CellMyelodysplastic SyndromesMyelodysplastic-Myeloproliferative DiseasesPrecancerous ConditionsHodgkin DiseaseLymphoma, T-Cell, CutaneousRecurrenceLymphoma, Large-Cell, AnaplasticImmunoblastic LymphadenopathyBurkitt LymphomaLymphoma, B-Cell, Marginal ZoneLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinLymphoma, Large-Cell, ImmunoblasticPrecursor Cell Lymphoblastic Leukemia-LymphomaPrecursor T-Cell Lymphoblastic Leukemia-LymphomaLymphoma, FollicularLymphoma, Mantle-CellLeukemia, Lymphocytic, Chronic, B-CellCongenital AbnormalitiesLeukemia, Myeloid, AcuteLeukemia, Myeloid, Accelerated PhaseLeukemia, Myeloid, Chronic-PhaseLeukemia, Myeloid, Chronic, Atypical, BCR-ABL NegativeLeukemia, Myelomonocytic, ChronicLeukemia, Myelomonocytic, JuvenilePrimary Myelofibrosis

Interventions

Antilymphocyte SerumCyclophosphamideEtoposidefludarabine phosphateMelphalanMethotrexateSirolimusTacrolimusHematopoietic Stem Cell TransplantationPeripheral Blood Stem Cell TransplantationWhole-Body Irradiation

Condition Hierarchy (Ancestors)

Bone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesImmune System DiseasesNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersLymphoma, T-CellDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLymphadenopathyEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesTumor Virus InfectionsLymphoma, B-CellLeukemia, LymphoidLeukemia, B-CellChronic DiseaseCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesLeukemia, MyeloidLeukemia, Myelogenous, Chronic, BCR-ABL Positive

Intervention Hierarchy (Ancestors)

Immune SeraAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsBiological ProductsComplex MixturesPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsPodophyllotoxinTetrahydronaphthalenesNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicPolycyclic CompoundsGlucosidesGlycosidesCarbohydratesPhenylalanineAmino Acids, AromaticAmino Acids, CyclicAmino AcidsAminopterinPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsMacrolidesLactonesStem Cell TransplantationCell TransplantationCell- and Tissue-Based TherapyBiological TherapyTherapeuticsTransplantationSurgical Procedures, OperativeRadiotherapyInvestigative Techniques

Results Point of Contact

Title
Dr. Ryotaro Nakamura
Organization
City of Hope Medical Center
rnakamura@coh.org
626-256-4673

Study Officials

  • Ryotaro Nakamura, MD

    City of Hope Comprehensive Cancer Center

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
SUPPORTIVE CARE
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 21, 2007

First Posted

January 9, 2008

Study Start

May 1, 2007

Primary Completion

February 1, 2012

Study Completion

February 1, 2012

Last Updated

September 10, 2014

Results First Posted

August 12, 2014

Record last verified: 2014-09

Locations

US(2)