NCT01116232

Brief Summary

This Phase II clinical trial was designed for patients with hematologic malignancies in need of donor peripheral blood stem cell transplant, and have no HLA matched donor. Therefore It will test the efficacy of combining sirolimus, tacrolimus, antithymocyte globulin, and rituximab in preventing graft versus host disease in transplants from HLA Haploidentical and partially mismatched donors.

Trial Health

57
Monitor

Trial Health Score

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

Enrollment
4

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Aug 2010

Typical duration 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

First Submitted

Initial submission to the registry

May 3, 2010

Completed
1 day until next milestone

First Posted

Study publicly available on registry

May 4, 2010

Completed
3 months until next milestone

Study Start

First participant enrolled

August 1, 2010

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2013

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2013

Completed
7 months until next milestone

Results Posted

Study results publicly available

December 13, 2013

Completed
Last Updated

March 26, 2019

Status Verified

March 1, 2019

Enrollment Period

2.8 years

First QC Date

May 3, 2010

Results QC Date

October 22, 2013

Last Update Submit

March 13, 2019

Conditions

Keywords

graft versus host diseaseaccelerated 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)atypical chronic myeloid leukemia, BCR-ABL negativeblastic phase chronic myelogenous leukemiachronic myelomonocytic leukemiachronic phase chronic myelogenous leukemiameningeal chronic myelogenous leukemiaprogressive hairy cell leukemia, initial treatmentprolymphocytic leukemiarecurrent adult acute lymphoblastic leukemiarecurrent adult acute myeloid leukemiarecurrent adult T-cell leukemia/lymphomarefractory chronic lymphocytic leukemiarefractory hairy cell leukemiarelapsing chronic myelogenous leukemiastage I adult T-cell leukemia/lymphomastage I chronic lymphocytic leukemiastage II adult T-cell leukemia/lymphomastage II chronic lymphocytic leukemiastage III adult T-cell leukemia/lymphomastage III chronic lymphocytic leukemiastage IV adult T-cell leukemia/lymphomastage IV chronic lymphocytic leukemiaT-cell large granular lymphocyte leukemiauntreated adult acute lymphoblastic leukemiauntreated adult acute myeloid leukemiauntreated hairy cell leukemiarecurrent adult Hodgkin lymphomastage I adult Hodgkin lymphomastage II adult Hodgkin lymphomastage III adult Hodgkin lymphomastage IV adult Hodgkin lymphomaanaplastic large cell lymphomaangioimmunoblastic T-cell lymphomacutaneous B-cell non-Hodgkin lymphomarecurrent cutaneous T-cell non-Hodgkin lymphomastage I cutaneous T-cell non-Hodgkin lymphomastage II cutaneous T-cell non-Hodgkin lymphomastage III cutaneous T-cell non-Hodgkin lymphomastage IV cutaneous T-cell non-Hodgkin lymphomarecurrent mycosis fungoides/Sezary syndromestage I mycosis fungoides/Sezary syndromestage II mycosis fungoides/Sezary syndromestage III mycosis fungoides/Sezary syndromestage IV mycosis fungoides/Sezary syndromeadult grade III lymphomatoid granulomatosisadult nasal type extranodal NK/T-cell lymphomaWaldenstrom macroglobulinemiaextranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissuenodal marginal zone B-cell lymphomasplenic marginal zone 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 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 grade 1 follicular lymphomastage I grade 2 follicular lymphomastage I grade 3 follicular lymphomastage I mantle cell lymphomastage I marginal zone lymphomastage I small lymphocytic 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 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 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 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 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 grade 1 follicular lymphomarecurrent grade 2 follicular lymphomarecurrent grade 3 follicular lymphomarecurrent mantle cell lymphomarecurrent marginal zone lymphomarecurrent small lymphocytic lymphomaintraocular lymphomapost-transplant lymphoproliferative disorderchronic eosinophilic leukemiachronic neutrophilic leukemiaprimary myelofibrosisstage I multiple myelomastage II multiple myelomastage III multiple myelomarefractory multiple myelomade novo myelodysplastic syndromespreviously treated myelodysplastic syndromesmyelodysplastic/myeloproliferative neoplasm, unclassifiable

Outcome Measures

Primary Outcomes (3)

  • Incidence and Severity of Acute Graft-vs-host Disease (GVHD)

    During the first six months post transplant

  • Time to Engraftment

    During the first six months post transplant

  • Safety Assessment

    During the first six months post transplant

Secondary Outcomes (5)

  • Incidence of Chronic GVHD

    Within two years after transplant

  • Incidence of Infections Including Cytomegalovirus, Epstein-Barr Virus Reactivation, and Post-transplant Lymphoproliferative Disorder

    At one year

  • Incidence of Thrombotic Microangiopathy

    Within 100 days of HCT

  • Overall and Disease-free Survival

    At 1 year

  • Immunocorrelative Studies Pre- and Periodically Post-transplantation

    Using flow cytometry at 30, 60, 90, and 180 days post transplant.

Study Arms (1)

anti-thymocyte globulin, rituximab, sirolimus, tacrolimus,

EXPERIMENTAL

anti-thymocyte globulin: Infuse the first dose over a minimum of 6 hours, and subsequent doses over a minimum of 4 hours via a 0.22 micron in-line filter Rituximab: The total dose chosen for this protocol is 28 mg/kg divided in two doses (14 mg/kg on days -7 and +3). Initial infusion: Start rate of 50 mg/hour; For adults, Sirolimus will be administered at 12 mg orally loading dose on day -3, followed by 4 mg orally single morning daily dose (target serum level 3-12 ng/ml by HPLC). Tacrolimus will be administered intravenously at a dose of 0.03 mg/kg (ideal body weight) q 24h by continuous infusion starting on Day -3. Intravenous Tacrolimus will be discontinued once the patient starts eating and the drug will then be given orally at a dose of approximately 4 times the intravenous dose.

Biological: anti-thymocyte globulinBiological: rituximabDrug: sirolimusDrug: tacrolimusOther: laboratory biomarker analysisProcedure: allogeneic hematopoietic stem cell transplantationProcedure: management of therapy complicationsProcedure: peripheral blood stem cell transplantation

Interventions

Infuse the first dose over a minimum of 6 hours, and subsequent doses over a minimum of 4 hours via a 0.22 micron in-line filter.

anti-thymocyte globulin, rituximab, sirolimus, tacrolimus,
rituximabBIOLOGICAL

The total dose chosen for this protocol is 28 mg/kg divided in two doses (14 mg/kg on days -7 and +3). Initial infusion: Start rate of 50 mg/hour; if there is no reaction, increase the rate by 50 mg/hour increments every 30 minutes, to a maximum rate of 400 mg/hour. Subsequent infusions: If patient did not tolerate initial infusion follow initial infusion guidelines. If patient tolerated initial infusion, start at 100 mg/hour; if there is no reaction, increase the rate by 100 mg/hour increments every 30 minutes, to a maximum rate of 400 mg/hour. Note: If a reaction occurs, slow or stop the infusion. If the reaction abates, restart infusion at 50% of the previous rate. In patients who tolerated the Rituximab well in the past, a rapid infusion rate can be used over 90 minutes with 20% of the dose administered in the first 30 minutes and the remaining 80% is given over 60 minutes.

Also known as: Rituxan®
anti-thymocyte globulin, rituximab, sirolimus, tacrolimus,

For adults, Sirolimus will be administered at 12 mg orally loading dose on day -3, followed by 4 mg orally single morning daily dose (target serum level 3-12 ng/ml by HPLC).

Also known as: Rapamune®
anti-thymocyte globulin, rituximab, sirolimus, tacrolimus,

Tacrolimus will be administered intravenously at a dose of 0.03 mg/kg (ideal body weight) q 24h by continuous infusion starting on Day -3. Intravenous Tacrolimus will be discontinued once the patient starts eating and the drug will then be given orally at a dose of approximately 4 times the intravenous dose.

Also known as: Prograf
anti-thymocyte globulin, rituximab, sirolimus, tacrolimus,

laboratory biomarker analysis

anti-thymocyte globulin, rituximab, sirolimus, tacrolimus,

allogeneic hematopoietic stem cell transplantation

anti-thymocyte globulin, rituximab, sirolimus, tacrolimus,

management of therapy complications

anti-thymocyte globulin, rituximab, sirolimus, tacrolimus,

peripheral blood stem cell transplantation

anti-thymocyte globulin, rituximab, sirolimus, tacrolimus,

Eligibility Criteria

Age18 Years - 120 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
DISEASE CHARACTERISTICS: * Diagnosis of a hematological malignancy, including: * Non-Hodgkin lymphoma * Hodgkin lymphoma * Acute myeloid leukemia or acute lymphoblastic leukemia * Myelodysplastic syndrome (treated or untreated) * Chronic myelogenous leukemia * Multiple myeloma * Chronic lymphocytic leukemia * Myelofibrosis and other myeloproliferative disorders * No suitable related HLA-matched or unrelated HLA-matched (8/8 or 7/8 matched) donor * Available suitable haploidentical or partial-matched unrelated donor (high-resolution molecular HLA typing is mandatory for HLA Class I and II) * No more than 4/8 HLA allele or antigen mismatch for a haploidentical-related first-degree family member donor * Only 6/8 or 5/8 allele or antigen match for an unrelated donor * Scheduled to undergo peripheral blood stem cell transplantation * Not receiving bone marrow or ex vivo engineered or processed graft (e.g., CD34+ enrichment, T-cell depletion) * No documented uncontrolled CNS disease PATIENT CHARACTERISTICS: * Karnofsky performance status (PS) 70-100% * ECOG PS 0-2 * Serum bilirubin \< 3 times upper limit of normal (ULN) * ALT and AST \< 3 times ULN * Creatinine clearance \> 60 mL/min * Ejection fraction \> 50% * Forced vital capacity, FEV\_1, or DLCO \> 50% predicted * Negative pregnancy test * Able to cooperate with oral medication intake * Patients with coronary heart disease (recent myocardial infarctions, angina, cardiac stent, or bypass surgery in the past 6 months) are eligible provided they are cleared with a stress echo or nuclear myocardial perfusions stress test and a cardiology consult * No ascites * No HIV positivity * No active hepatitis B or C virus infection * No known contraindication to the administration of sirolimus, tacrolimus, anti-thymocyte globulin, or rituximab PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Not on home oxygen

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

Sponsors & Collaborators

Study Sites (1)

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Related Links

MeSH Terms

Conditions

Myeloproliferative DisordersGraft vs Host DiseaseLeukemiaLymphomaLymphoproliferative DisordersMultiple MyelomaNeoplasms, Plasma CellMyelodysplastic SyndromesMyelodysplastic-Myeloproliferative DiseasesLeukemia, Myeloid, Accelerated PhaseCongenital AbnormalitiesLeukemia, Myeloid, Chronic, Atypical, BCR-ABL NegativeBlast CrisisLeukemia, Myelomonocytic, ChronicLeukemia, Myeloid, Chronic-PhaseLeukemia, ProlymphocyticPrecursor Cell Lymphoblastic Leukemia-LymphomaLeukemia, Myeloid, AcutePrecursor T-Cell Lymphoblastic Leukemia-LymphomaLeukemia, Lymphocytic, Chronic, B-CellLeukemia, Hairy CellLeukemia, Large Granular LymphocyticHodgkin DiseaseLymphoma, Large-Cell, AnaplasticImmunoblastic LymphadenopathyLymphoma, T-Cell, CutaneousMycosis FungoidesSezary SyndromeLymphoma, Extranodal NK-T-CellWaldenstrom MacroglobulinemiaLymphoma, B-Cell, Marginal ZoneBurkitt LymphomaLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinLymphoma, Large-Cell, ImmunoblasticLymphoma, FollicularLymphoma, Mantle-CellIntraocular LymphomaPdgfra-Associated Chronic Eosinophilic LeukemiaLeukemia, Neutrophilic, ChronicPrimary Myelofibrosis

Interventions

Antilymphocyte SerumRituximabSirolimusTacrolimusPeripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Bone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesImmune System DiseasesNeoplasms by Histologic TypeNeoplasmsLymphatic DiseasesImmunoproliferative DisordersHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersLeukemia, Myelogenous, Chronic, BCR-ABL PositiveLeukemia, MyeloidChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesCell Transformation, NeoplasticCarcinogenesisNeoplastic ProcessesLeukemia, LymphoidLeukemia, B-CellLeukemia, T-CellLymphoma, T-CellLymphadenopathyLymphoma, B-CellEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsEye NeoplasmsNeoplasms by Site

Intervention Hierarchy (Ancestors)

Immune SeraAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsBiological ProductsComplex MixturesAntibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalMacrolidesLactonesOrganic ChemicalsHematopoietic Stem Cell TransplantationStem Cell TransplantationCell TransplantationCell- and Tissue-Based TherapyBiological TherapyTherapeuticsTransplantationSurgical Procedures, Operative

Limitations and Caveats

Study terminated due to lack of funding. No analysis, patient data on this protocol due to the fact that only four patients was able to be accrued.

Results Point of Contact

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

Study Officials

  • Zaid Al-Kadhimi, M.D.

    Barbara Ann Karmanos Cancer Institute

    PRINCIPAL INVESTIGATOR

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

May 3, 2010

First Posted

May 4, 2010

Study Start

August 1, 2010

Primary Completion

May 1, 2013

Study Completion

June 1, 2013

Last Updated

March 26, 2019

Results First Posted

December 13, 2013

Record last verified: 2019-03

Locations