NCT01652014

Brief Summary

This study will determine the safety and applicability of experimental forms of umbilical cord blood (UCB) transplantation for patients with high risk hematologic malignancies who might benefit from a hematopoietic stem cell transplant (HSCT) but who do not have a standard donor option (no available HLA-matched related donor (MRD), HLA-matched unrelated donor (MUD)), or single UCB unit with adequate cell number and HLA-match).

Trial Health

30
At Risk

Trial Health Score

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

Trial has exceeded expected completion date
Timeline
Completed

Started Jan 2014

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
withdrawn

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

July 20, 2012

Completed
7 days until next milestone

First Posted

Study publicly available on registry

July 27, 2012

Completed
1.4 years until next milestone

Study Start

First participant enrolled

January 1, 2014

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2017

Completed
Last Updated

July 14, 2016

Status Verified

July 1, 2016

Enrollment Period

3 years

First QC Date

July 20, 2012

Last Update Submit

July 13, 2016

Conditions

Accelerated Phase Chronic Myelogenous LeukemiaAcute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic SyndromeAdult 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)Adult Nasal Type Extranodal NK/T-cell LymphomaAnaplastic Large Cell LymphomaAngioimmunoblastic T-cell LymphomaBlastic Phase Chronic Myelogenous LeukemiaCutaneous B-cell Non-Hodgkin Lymphomade Novo Myelodysplastic SyndromesExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissueHepatosplenic T-cell LymphomaIntraocular LymphomaMyelodysplastic/Myeloproliferative Neoplasm, UnclassifiableNodal Marginal Zone B-cell LymphomaNoncutaneous Extranodal LymphomaPeripheral T-cell LymphomaPost-transplant Lymphoproliferative DisorderPreviously 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 Hodgkin LymphomaRecurrent 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 LeukemiaRefractory Hairy Cell LeukemiaRefractory Multiple MyelomaRelapsing Chronic Myelogenous LeukemiaSecondary Acute Myeloid LeukemiaSecondary Myelodysplastic SyndromesSmall Intestine LymphomaSplenic Marginal Zone LymphomaT-cell Large Granular Lymphocyte LeukemiaTesticular LymphomaWaldenström Macroglobulinemia

Keywords

TransplantationHematopoietic Stem Cell Transplantation

Outcome Measures

Primary Outcomes (2)

  • Engraftment of white blood cells (WBC) (absolute neutrophil count > 500/mm^3)

    3 years

  • Non-relapse mortality

    40 months

Secondary Outcomes (7)

  • Platelet engraftment rate (non-transfusion dependent)

    At 100 days

  • Transplant related mortality

    At 1 year

  • Rates of infection requiring hospitalization or prolongation of hospitalization

    Up to 2 years

  • Incidence of steroid-refractory acute GVHD

    at 100 days

  • Incidence of extensive chronic GVHD

    up to 2 years

  • +2 more secondary outcomes

Study Arms (2)

Arm I

EXPERIMENTAL

Double UCB transplantation Patients receive conditioning comprising fludarabine phosphate IV over 30 minutes on days -6 to -2, cyclophosphamide IV over 1 hour on day -6, and undergo TBI on day -1. Patients also receive GVHD prophylaxis comprising tacrolimus IV continuously or PO beginning on day -3 with taper and mycophenolate mofetil PO BID days 1-30. Patients undergo double allogeneic UCB transplant on day 0.

Drug: cyclophosphamideDrug: fludarabine phosphateDrug: mycophenolate mofetilProcedure: allogeneic hematopoietic stem cell transplantationProcedure: double-unit umbilical cord blood transplantationRadiation: total-body irradiationDrug: tacrolimus

Arm II

EXPERIMENTAL

Sub-threshold single UCB + irradiated PBMCs transplantation Patients receive conditioning comprising fludarabine phosphate IV over 30 minutes on days -6 to -2, cyclophosphamide IV over 1 hour on day -6, and undergo TBI on day -1. Patients also receive GVHD prophylaxis comprising tacrolimus IV continuously or PO beginning on day -3 with taper and mycophenolate mofetil PO BID days 1-30. Patients undergo single allogeneic UCB transplant on day 0. Patients also undergo irradiated allogeneic PBMC transplant within 8 hours following the UCB infusion.

Drug: cyclophosphamideDrug: fludarabine phosphateDrug: mycophenolate mofetilProcedure: umbilical cord blood transplantationRadiation: total-body irradiationDrug: tacrolimusProcedure: allogeneic hematopoietic stem cell transplantationProcedure: peripheral blood stem cell transplantation

Interventions

Given IV over 1 hour on Day -6; after pre-hydration

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana
Arm IArm II

Given IV daily over 30 minutes for 5 days (Days -6 to -2)

Also known as: 2-F-ara-AMP, Beneflur, Fludara
Arm IArm II

Given PO 1.0 g BID Day 1-30

Also known as: Cellcept, MMF
Arm IArm II

Undergo double-unit allogeneic UCB transplant

Arm I

Undergo single allogeneic UCB transplant

Also known as: cord blood transplantation, transplantation, umbilical cord blood, UCB transplantation
Arm II

Undergo double-unit allogeneic UCB transplant

Arm I

Undergo TBI

Also known as: TBI
Arm IArm II

Given IV 0.03 mg/kg/d as continuous infusion over 24 hours starting Day -3 with dose adjustments to maintain level of 8-20 mg/ml

Also known as: FK 506, Prograf
Arm IArm II

Undergo irradiated allogeneic peripheral blood stem cell transplant

Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell
Arm II

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with histologically proven hematologic malignancy with anticipated 2 year survival \< 20% with standard therapy; patients age \<18 are excluded by virtue of the policies and procedures of the allogeneic hematopoietic stem cell transplant (HSCT) program (Cancer Institute of New Jersey \[CINJ\]/Robert Wood Johnson University Hospital \[RWJUH\] is not an approved Pediatric Transplant Center); patients \> age 65 are generally not considered candidates for experimental unrelated allogeneic HSCT, as utilized in this study by virtue of the anticipated delayed immune reconstitution, high risk of GVHD, and known negative impact of age on outcomes
  • Patients eligible for this trial will have high risk diseases that include, but are not limited to:
  • Acute myeloid leukemia (AML) in second complete remission (CR2) or greater or early relapse with \< 5% marrow blasts and no circulating blasts
  • AML in first complete remission (CR1) with high risk cytogenetics (complex, monosomy 5, monosomy 7, 11q23 (not t(9;11)), t(6;9), chromosome 3, monosomy phenotype and other karyotypes estimated to have =\< 20% disease free survival at 3 years) or secondary/transformed AML without favorable cytogenetics;
  • Acute lymphoblastic leukemia (ALL) with t(9;22), 11q23 abnormality or early relapse (\< 5% marrow blasts) or CR2 or greater;
  • Chronic myeloid leukemia (CML) resistant/refractory to all commercially available Abelson (abl) kinase inhibitors (e.g. imatinib mesylate, dasatinib, nilotinib) or predicted to be so based upon clinical course or abl kinase domain mutation analysis; or in accelerated phase or blast crisis;
  • High intermediate to high international prognostic score myelodysplasia;
  • Non-Hodgkin lymphoma (NHL)/Hodgkin lymphoma (HL)/other lymphoproliferative diseases resistant/refractory to standard therapies and for whom an autologous transplant is considered to be inappropriate (e.g. bone marrow involvement, chemotherapy refractory disease, prior transplant);
  • Chronic lymphocytic leukemia (CLL) resistant/refractory to standard therapies (e.g. fludarabine) or high risk cytogenetics/fluorescence in situ hybridization (FISH) (e.g. 17p-);
  • Myeloproliferative disorders with progressive disease or cytopenias or clinical symptoms refractory to standard therapy (e.g. hypomethylating agents)
  • Relapsed or refractory multiple myeloma after (or not eligible for) high dose chemotherapy/autologous hematopoietic stem cell rescue and following salvage therapy with thalidomide, lenalidomide or bortezomib/other Food and Drug Administration (FDA)-approved multiple myeloma salvage therapies;
  • Other hematologic malignancies/disorders with anticipated 2 year survival \< 20%, as established by available data bases, medical literature and the documented consensus of the Hematologic Malignancies Tumor Study Group
  • Patients must be an allogeneic HSCT candidate but have no standard donor (matched related donor \[MRD\], human leukocyte antigen \[HLA\]-matched unrelated donor \[MUD\] or single UCB unit of appropriate size and HLA type) available
  • Patients must have available UCB unit(s)
  • Patients considered for Arm 2 must not be eligible for Arm 1 and must have an HLA-haploidentical sibling, parent, child, or other relative (uncle, aunt, first cousin, niece or nephew) who meets donor requirements as outlined in Donor Eligibility criteria
  • +20 more criteria

You may not qualify if:

  • Prior extensive radiation therapy that the radiation oncologist feels precludes additional TBI
  • Patients with known human immunodeficiency virus (HIV) are excluded due to side effects of the therapy on the immune system
  • Patients with known active central nervous system (CNS) disease will be excluded from this clinical trial because they often develop progressive neurologic dysfunction unresponsive to HSCT therapy

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Accelerated PhaseCongenital AbnormalitiesLymphoma, Extranodal NK-T-CellLymphoma, Large-Cell, AnaplasticImmunoblastic LymphadenopathyBlast CrisisIntraocular LymphomaMyeloproliferative DisordersLymphoma, B-Cell, Marginal ZoneLymphoma, T-Cell, PeripheralPrecursor Cell Lymphoblastic Leukemia-LymphomaLeukemia, Myeloid, AcuteBurkitt LymphomaLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinHodgkin DiseaseLymphoma, Large-Cell, ImmunoblasticPrecursor T-Cell Lymphoblastic Leukemia-LymphomaLymphoma, T-Cell, CutaneousLymphoma, FollicularLymphoma, Mantle-CellMycosis FungoidesSezary SyndromeLeukemia, Lymphocytic, Chronic, B-CellLeukemia, Hairy CellMultiple MyelomaLeukemia, Large Granular LymphocyticWaldenstrom Macroglobulinemia

Interventions

Cyclophosphamidefludarabine phosphateMycophenolic AcidCord Blood Stem Cell TransplantationTransplantationWhole-Body IrradiationTacrolimusPeripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Leukemia, Myelogenous, Chronic, BCR-ABL PositiveLeukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsBone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesLymphoma, T-CellLymphomaLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLymphadenopathyCell Transformation, NeoplasticCarcinogenesisNeoplastic ProcessesEye NeoplasmsNeoplasms by SiteLymphoma, B-CellLeukemia, LymphoidEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLeukemia, B-CellNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersLeukemia, T-Cell

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsCaproatesAcids, AcyclicCarboxylic AcidsFatty AcidsLipidsStem Cell TransplantationCell TransplantationCell- and Tissue-Based TherapyBiological TherapyTherapeuticsSurgical Procedures, OperativeRadiotherapyInvestigative TechniquesMacrolidesLactonesHematopoietic Stem Cell Transplantation

Study Officials

  • Roger Strair

    Rutgers Cancer Institute of New Jersey

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 20, 2012

First Posted

July 27, 2012

Study Start

January 1, 2014

Primary Completion

January 1, 2017

Study Completion

January 1, 2017

Last Updated

July 14, 2016

Record last verified: 2016-07

Locations