NCT00617929

Brief Summary

RATIONALE: Antithymocyte globulin, clofarabine, and rituximab may stop the patient's immune system from rejecting the donor's stem cells when they do not exactly match the patient's blood. 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 antithymocyte globulin before transplant and cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening. PURPOSE: This phase II trial is studying how well giving antithymocyte globulin together with clofarabine and rituximab works in treating patients after an unsuccessful stem cell transplant.

Trial Health

57
Monitor

Trial Health Score

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

Enrollment
12

participants targeted

Target at below P25 for phase_2 cancer

Timeline
Completed

Started Jan 2008

Longer than P75 for phase_2 cancer

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

January 1, 2008

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

February 15, 2008

Completed
3 days until next milestone

First Posted

Study publicly available on registry

February 18, 2008

Completed
6.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2014

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2015

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

January 20, 2017

Completed
Last Updated

December 28, 2017

Status Verified

December 1, 2017

Enrollment Period

6.8 years

First QC Date

February 15, 2008

Results QC Date

September 28, 2016

Last Update Submit

December 3, 2017

Conditions

Cancer

Keywords

chronic myelogenous leukemiaacute lymphoblastic leukemiachronic myeloid leukemialymphoblastic leukemiaacute myeloid leukemiachronic eosinophilic leukemiaprimary myelofibrosischronic myelomonocytic leukemiachronic neutrophilic leukemiade novo myelodysplastic syndromesdisseminated neuroblastomajuvenile myelomonocytic leukemiaBurkitt lymphomarhabdomyosarcomamyelodysplastic syndromesHodgkin lymphomalymphoblastic lymphomabreast cancerfollicular lymphomamantle cell lymphomamarginal zone lymphomarecurrent neuroblastomarecurrent ovarian epithelial cancerrecurrent ovarian germ cell tumorrecurrent small lymphocytic lymphomarecurrent malignant testicular germ cell tumorrecurrent Wilms tumor and other childhood kidney tumorsrecurrent/refractory childhood Hodgkin lymphomarefractory hairy cell leukemiarefractory multiple myelomarelapsing chronic myelogenous leukemiasecondary acute myeloid leukemiasecondary myelodysplastic syndromessplenic marginal zone lymphomastage I multiple myelomastage II multiple myelomastage III multiple myelomastage II ovarian epithelial cancerstage 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 chronic lymphocytic leukemiastage III grade 1 follicular lymphomastage III grade 2 follicular lymphomastage III grade 3 follicular lymphomastage III mantle cell lymphomastage III marginal zone lymphomastage III ovarian epithelial cancerstage III small lymphocytic lymphomastage III malignant testicular germ cell tumorstage IIIA breast cancerstage IIIB breast cancerstage IIIC breast cancerstage 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 breast cancerstage IV chronic lymphocytic leukemiastage IV grade 1 follicular lymphomastage IV grade 2 follicular lymphomastage IV grade 3 follicular lymphomastage IV mantle cell lymphomastage IV marginal zone lymphomastage IV ovarian epithelial cancerstage IV small lymphocytic lymphomarefractory chronic lymphocytic leukemia

Outcome Measures

Primary Outcomes (2)

  • Rate of Sustained Donor Engraftment

    Rate of Sustained Donor Engraftment is defined as the percent of paticipants with an absolute neutrophile count (ANC) of 500 or more without a subsequent graft rejection.

    Day 42 post transplantation

  • Survival at 100 Days Post Transplant

    Percent of patients alive from beginning of study to Day 100 post transplantation

    Day 100 post transplantation

Secondary Outcomes (5)

  • Treatment-related Death

    Day 100 post transplantation

  • Time to Primary Neutrophil Engraftment

    Day 42 post transplantation

  • Survival

    One year post transplantation

  • Chimerism

    Day 28 post transplantation

  • Acute Graft-vs-host Disease

    Day 30-100

Study Arms (1)

Conditioning for Graft Failure

EXPERIMENTAL

Primary or secondary graft failure after hematopoietic stem cell transplantation defined as a \> 50% loss of previously best donor chimerism or less than 25% donor chimerism beyond day +42 with pancytopenia and no evidence of relapse. Patients with any diagnosis, type of donor, hematopoietic cell graft or conditioning regimen should be considered for this study. Patients receive anti-thymocyte globulin, rituximab, and clofarabine.

Biological: anti-thymocyte globulinBiological: rituximabDrug: clofarabineProcedure: stem cell transplantation

Interventions

anti-thymocyte globulinBIOLOGICAL

administer 3 mg/kg intravenously (IV) over 4 hours on days -6, -5 and -4.

Also known as: Thymoglobulin®
Conditioning for Graft Failure
rituximabBIOLOGICAL

administered 375 mg/m\^2 intravenously (IV) in 1 mg/mL normal saline on day -7.

Also known as: Rituxan(R)
Conditioning for Graft Failure
clofarabineDRUG

administered 30 mg/m\^2 intravenously (IV) over 1 hour on Days -4, -3, and -2.

Also known as: CLOLARâ„¢
Conditioning for Graft Failure
stem cell transplantationPROCEDURE

administered on Day 0 per institutional guidelines.

Conditioning for Graft Failure

Eligibility Criteria

Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Timing of relevant evaluations: Taking in account the need for rapid intervention, if white blood count is less than 200 on day +20, bone marrow aspirate should be performed on day +21. Unless there is an increase in absolute neutrophil count (ANC) to \> 500 in the following 7 days, bone marrow aspirate should be repeated on day +28. If the white blood count is still less than 200 and bone marrow is acellular, bone marrow (BM) or peripheral blood stem cell (PBSC) donor should be reactivated and availability of cord blood (CB) units assessed. If the BM or PBSC donor is not confirmed within 14 days of the request for the donation (typically second donation from the same donor), CB unit should be used instead.
  • Primary or secondary graft failure after hematopoietic stem cell transplantation defined as a \> 50% loss of donor chimerism from previous maximum or less than 25% donor beyond day +42 with pancytopenia and no evidence of relapse. Patients with any diagnosis, type of donor, hematopoietic cell graft or conditioning regimen should be considered for this study.
  • primary graft failure is defined as:
  • ANC \< 500
  • BM \< 10% on two occasions (Day +21 and Day +28)
  • Donor chimerism need not to be considered, provided there is no evidence of malignancy
  • secondary graft failure is defined as \< 5% cellularity and ANC \< 500 for more than 7 days any time after primary engraftment).
  • Women of childbearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device \[IUD\], surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of treatment.
  • Patients or their guardian are able and willing to provide written informed consent.

You may not qualify if:

  • The presence of any of the following excludes a patient from study enrollment:
  • Uncontrolled active infection defined as more than one week with no response to appropriately chosen antibiotics
  • Evidence of recurrence of primary malignancy.
  • Pregnant or lactating. The agents used in this study may be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy. Women of childbearing age must use appropriate methods as described.
  • Allergy to rituximab.
  • Evidence of HIV infection or positive HIV serology.
  • Autologous recovery defined as defined as greater than 90% recipient PCR product in the competitive VNTR PCR performed on gradually increasing white blood cell count.
  • Related donors must be 2-75 years of age and in good health.
  • Meets match criteria
  • Able and willing to undergo cell collection procedures (bone marrow cell collection or leukapheresis)
  • Not pregnant or lactating.
  • HIV-1, HIV-2 negative; HTLV-1, HTLV-2 negative, Hepatitis B and C negative.
  • Patients or their guardian are able and willing to provide informed consent

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

NeoplasmsLeukemia, Myelogenous, Chronic, BCR-ABL PositivePrecursor Cell Lymphoblastic Leukemia-LymphomaLeukemia, Myeloid, AcutePdgfra-Associated Chronic Eosinophilic LeukemiaPrimary MyelofibrosisLeukemia, Myelomonocytic, ChronicLeukemia, Neutrophilic, ChronicLeukemia, Myelomonocytic, JuvenileBurkitt LymphomaRhabdomyosarcomaMyelodysplastic SyndromesHodgkin DiseaseBreast NeoplasmsLymphoma, FollicularLymphoma, Mantle-CellLymphoma, B-Cell, Marginal ZoneNeuroblastomaCarcinoma, Ovarian EpithelialLeukemia, Lymphocytic, Chronic, B-CellTesticular NeoplasmsWilms TumorRecurrenceLeukemia, Hairy CellMultiple MyelomaLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinLymphoma, Large-Cell, Immunoblastic

Interventions

Antilymphocyte SerumthymoglobulinRituximabClofarabineStem Cell Transplantation

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeMyeloproliferative DisordersBone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLeukemia, LymphoidLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesMyelodysplastic-Myeloproliferative DiseasesEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLymphoma, B-CellLymphomaMyosarcomaNeoplasms, Muscle TissueNeoplasms, Connective and Soft TissueSarcomaNeoplasms by SiteBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesNeuroectodermal Tumors, Primitive, PeripheralNeuroectodermal Tumors, PrimitiveNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms, Glandular and EpithelialNeoplasms, Nerve TissueCarcinomaOvarian NeoplasmsEndocrine Gland NeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal DisordersLeukemia, B-CellGenital Neoplasms, MaleGenital Diseases, MaleMale Urogenital DiseasesTesticular DiseasesNeoplasms, Complex and MixedKidney NeoplasmsUrologic NeoplasmsNeoplastic Syndromes, HereditaryKidney DiseasesUrologic DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Immune SeraAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsBiological ProductsComplex MixturesAntibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAdenine NucleotidesPurine NucleotidesPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsArabinonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesNucleotidesRibonucleotidesCell TransplantationCell- and Tissue-Based TherapyBiological TherapyTherapeuticsTransplantationSurgical Procedures, Operative

Results Point of Contact

Title
Jakub Tolar, MD
Organization
Masonic Cancer Center, University of Minnesota
tolar003@umn.edu
612-624-7180

Study Officials

  • Jakub Tolar, MD

    Masonic Cancer Center, University of Minnesota

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

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

February 15, 2008

First Posted

February 18, 2008

Study Start

January 1, 2008

Primary Completion

October 1, 2014

Study Completion

October 1, 2015

Last Updated

December 28, 2017

Results First Posted

January 20, 2017

Record last verified: 2017-12

Locations

US(1)