NCT00049504

Brief Summary

This phase II trial studies how well giving fludarabine phosphate, cyclophosphamide, tacrolimus, mycophenolate mofetil and total-body irradiation together with a donor bone marrow transplant works in treating patients with high-risk hematologic cancer. Giving low doses of chemotherapy, such as fludarabine phosphate and cyclophosphamide, and total-body irradiation before a donor bone marrow transplant helps stop the growth of cancer cells by stopping them from dividing or killing them. Giving cyclophosphamide after transplant may also stop the patient's immune system from rejecting the donor's bone marrow stem cells. The donated stem cells may replace the patient's immune system 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 and mycophenolate mofetil after the transplant may stop this from happening

Trial Health

87
On Track

Trial Health Score

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

Enrollment
53

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Jan 2002

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

January 1, 2002

Completed
11 months until next milestone

First Submitted

Initial submission to the registry

November 12, 2002

Completed
3 months until next milestone

First Posted

Study publicly available on registry

January 27, 2003

Completed
8.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2011

Completed
2.9 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2014

Completed
3.3 years until next milestone

Results Posted

Study results publicly available

May 17, 2017

Completed
Last Updated

May 17, 2017

Status Verified

April 1, 2017

Enrollment Period

9.2 years

First QC Date

November 12, 2002

Results QC Date

April 10, 2017

Last Update Submit

April 10, 2017

Conditions

Accelerated 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 Del(5q)Adult 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 LymphomaChildhood Acute Lymphoblastic Leukemia in RemissionChildhood Acute Myeloid Leukemia in RemissionChildhood Burkitt LymphomaChildhood Chronic Myelogenous LeukemiaChildhood Myelodysplastic SyndromesChildhood Nasal Type Extranodal NK/T-cell LymphomaCutaneous B-cell Non-Hodgkin Lymphomade Novo Myelodysplastic SyndromesExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissueHematopoietic/Lymphoid CancerHepatosplenic T-cell LymphomaIntraocular LymphomaNodal Marginal Zone B-cell LymphomaPeripheral T-cell LymphomaPost-transplant Lymphoproliferative DisorderPreviously Treated Myelodysplastic SyndromesRecurrent 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 Childhood Anaplastic Large Cell LymphomaRecurrent Childhood Grade III Lymphomatoid GranulomatosisRecurrent Childhood Large Cell LymphomaRecurrent Childhood Lymphoblastic LymphomaRecurrent Childhood Small Noncleaved Cell 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 LymphomaRecurrent/Refractory Childhood Hodgkin LymphomaRefractory Chronic Lymphocytic LeukemiaRefractory Multiple MyelomaRelapsing Chronic Myelogenous LeukemiaSecondary Myelodysplastic SyndromesSmall Intestine LymphomaSplenic Marginal Zone LymphomaStage II Multiple MyelomaStage 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 Adult T-cell Leukemia/LymphomaStage III Childhood Hodgkin LymphomaStage III Chronic Lymphocytic LeukemiaStage III Cutaneous T-cell Non-Hodgkin 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 Multiple MyelomaStage III Mycosis Fungoides/Sezary SyndromeStage 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 Adult T-cell Leukemia/LymphomaStage IV Childhood Hodgkin LymphomaStage IV Chronic Lymphocytic LeukemiaStage IV Cutaneous T-cell Non-Hodgkin 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 Mycosis Fungoides/Sezary SyndromeStage IV Small Lymphocytic LymphomaTesticular LymphomaWaldenström Macroglobulinemia

Outcome Measures

Primary Outcomes (3)

  • Donor Engraftment (Chimerism)

    Defined by the detection of at least 50% donor derived T-cells (CD3+), as a proportion of the total T-cell population

    At day +84 after transplantation

  • Incidence of Grades III-IV Acute GVHD

    Grade III GVHD represents moderate severity. Grade IV GVHD represents extreme severity

    At any time within 200 days after transplantation

  • Non-relapse-related Mortality

    Number of deaths without progression or recurrence of malignant disease

    Up to 200 days after transplantation

Study Arms (1)

Treatment (nonmyeloablative HSCT)

EXPERIMENTAL

NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate IV over 1 hour on days -6 to -2 and cyclophosphamide IV over 1 hour on days -6 and -5. Patients undergo total body irradiation on day -1. TRANSPLANTATION: Patients undergo BMT, from an HLA-haploidentical donor, on day 0. POST-TRANSPLANT IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on day 3. GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV over 1-2 hours and then tacrolimus PO, once tolerated, on days 4-180, with taper on day 86 in the absence of graft-versus-host disease. Patients also receive mycophenolate mofetil PO three times daily on days 4-35.

Drug: cyclophosphamideDrug: fludarabine phosphateDrug: tacrolimusDrug: mycophenolate mofetilGenetic: polymerase chain reactionGenetic: fluorescence in situ hybridizationGenetic: polymorphism analysisGenetic: gene expression analysisRadiation: total-body irradiationProcedure: allogeneic bone marrow transplantationProcedure: allogeneic hematopoietic stem cell transplantation

Interventions

cyclophosphamideDRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana
Treatment (nonmyeloablative HSCT)
fludarabine phosphateDRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, Fludara
Treatment (nonmyeloablative HSCT)
tacrolimusDRUG

Given IV or orally

Also known as: FK 506, Prograf
Treatment (nonmyeloablative HSCT)
mycophenolate mofetilDRUG

Given orally

Also known as: Cellcept, MMF
Treatment (nonmyeloablative HSCT)
polymerase chain reactionGENETIC

Correlative studies

Also known as: PCR
Treatment (nonmyeloablative HSCT)
fluorescence in situ hybridizationGENETIC

Correlative studies

Also known as: fluorescence in situ hybridization (FISH)
Treatment (nonmyeloablative HSCT)
polymorphism analysisGENETIC

Correlative studies

Treatment (nonmyeloablative HSCT)
gene expression analysisGENETIC

Correlative studies

Treatment (nonmyeloablative HSCT)
total-body irradiationRADIATION

Undergo total-body irradiation

Also known as: TBI
Treatment (nonmyeloablative HSCT)
allogeneic bone marrow transplantationPROCEDURE

Undergo haploidentical hematopoietic bone marrow transplantation

Also known as: bone marrow therapy, allogeneic, bone marrow therapy, allogenic, transplantation, allogeneic bone marrow, transplantation, allogenic bone marrow
Treatment (nonmyeloablative HSCT)
allogeneic hematopoietic stem cell transplantationPROCEDURE

Undergo haploidentical hematopoietic bone marrow transplantation

Treatment (nonmyeloablative HSCT)

Eligibility Criteria

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

You may qualify if:

  • Chronic myeloid leukemia (CML) in accelerated phase (AP)
  • Acute myeloid leukemia (AML) with high-risk cytogenetics \[del(5q)/-5, del(7q)/-7, abnormal 3q, 9q, 11q, 20q, 21q, 17p, t(6:9), t(9;22), complex karyotypes (\>= 3 abnormalities)\] in complete remission (CR)1
  • AML \>= CR2; patients should have \< 5% marrow blasts at the time of transplant
  • High-risk ALL defined as: CR1 with high-risk cytogenetics; t(9;22), t(4;11), or hypodiploid (\< 45 chromosomes) for pediatric patients; t(9;22), t(8;14), t(4;11), t(1;19) for adult patients; \> 4 wk to achieve CR1; \>= CR2 (patients should have \< 5% marrow blasts at the time of transplant)
  • Myelodysplastic syndromes (MDS) (\>int-1 per IPSS) after \>= 1 prior cycle of induction chemotherapy; should have \< 5% marrow blasts at the time of transplant
  • Multiple myeloma (MM) Stage II or III patients who have progressed after an initial response to chemotherapy or autologous hematopoietic stem cell transplantation (HSCT) or MM patients with refractory disease who may benefit from tandem autologous-nonmyeloablative allogeneic transplant
  • Chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL) or Hodgkin's Disease (HD) who are ineligible for autologous HSCT or who have resistant/refractory disease and who may benefit from tandem autologous nonmyeloablative allogeneic transplant
  • Patients who have received a prior allogeneic HSCT and who have either rejected their grafts or who have become tolerant of their grafts with no active graft-versus-host disease (GvHD) requiring immunosuppressive therapy
  • DONOR: Related donors who are identical for one HLA haplotype and mismatched at the HLA-A, -B, -C or DRB1 loci of the unshared haplotype with the exception of single HLA-A, -B or -C allele mismatches

You may not qualify if:

  • Cross-match positive with donor
  • Patients with suitably matched related or unrelated donors
  • Patients with conventional transplant options (a conventional transplant should be the priority for eligible patients =\< 50 yr of age who have a related donor mismatched for a single HLA-A, -B or DRB1 antigen)
  • Central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy
  • Presence of active, serious infection (e.g., mucormycosis, uncontrolled aspergillosis, tuberculosis)
  • Karnofsky Performance Status \< 60 for adult patients
  • Lansky-Play Performance Score \< 60 for pediatric patients
  • Left ventricular ejection fraction \< 35%
  • Diffusing capacity of the lung for carbon monoxide (DLCO) \< 35% and/or receiving supplemental continuous oxygen
  • Liver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction as evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin \> 3 mg/dL or symptomatic biliary disease
  • Human immunodeficiency virus (HIV)-positive patients
  • Women of childbearing potential who are pregnant (beta-HCG+) or breast feeding
  • Fertile men and women unwilling to use contraceptives during and for 12 months post-transplant
  • Life expectancy severely limited by diseases other than malignancy
  • DONOR: Donor-recipient pairs in which the HLA-mismatch is only in the HVG direction
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Accelerated PhaseCongenital AbnormalitiesLymphoma, Extranodal NK-T-CellLymphoma, Large-Cell, AnaplasticImmunoblastic LymphadenopathyBurkitt LymphomaHematologic NeoplasmsIntraocular LymphomaLymphoma, B-Cell, Marginal ZoneLymphoma, T-Cell, PeripheralLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinHodgkin DiseaseLymphoma, Large-Cell, ImmunoblasticPrecursor Cell Lymphoblastic Leukemia-LymphomaPrecursor T-Cell Lymphoblastic Leukemia-LymphomaDendritic Cell Sarcoma, InterdigitatingLymphoma, T-Cell, CutaneousLymphoma, FollicularLymphoma, Mantle-CellMycosis FungoidesSezary SyndromeLeukemia, Lymphocytic, Chronic, B-CellRecurrenceMultiple MyelomaWaldenstrom Macroglobulinemia

Interventions

Cyclophosphamidefludarabine phosphateTacrolimusMycophenolic AcidPolymerase Chain ReactionIn Situ Hybridization, FluorescenceAmplified Fragment Length Polymorphism AnalysisGene Expression ProfilingWhole-Body IrradiationTransplantation

Condition Hierarchy (Ancestors)

Leukemia, Myelogenous, Chronic, BCR-ABL PositiveLeukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsMyeloproliferative DisordersBone 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 DiseasesLymphadenopathyEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLymphoma, B-CellNeoplasms by SiteEye NeoplasmsLeukemia, LymphoidHistiocytic Disorders, MalignantHistiocytosisLeukemia, B-CellNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsMacrolidesLactonesCaproatesAcids, AcyclicCarboxylic AcidsFatty AcidsLipidsNucleic Acid Amplification TechniquesGenetic TechniquesInvestigative TechniquesIn Situ HybridizationStaining and LabelingHistocytological Preparation TechniquesCytological TechniquesClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisHistological TechniquesCytogenetic AnalysisNucleic Acid HybridizationDNA FingerprintingRadiotherapyTherapeuticsSurgical Procedures, Operative

Results Point of Contact

Title
Rachel Salit
Organization
Fred Hutchinson Cancer Research Center
rsalit@fredhutch.gov
206-667-1317

Study Officials

  • Paul O'Donnell

    Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    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

November 12, 2002

First Posted

January 27, 2003

Study Start

January 1, 2002

Primary Completion

March 1, 2011

Study Completion

February 1, 2014

Last Updated

May 17, 2017

Results First Posted

May 17, 2017

Record last verified: 2017-04

Data Sharing

IPD Sharing
Will not share

Individual patient data is protected by HIPAA at each participant organization.

Locations

US(1)