NCT01529827

Brief Summary

This phase II trial studies how well giving fludarabine phosphate, melphalan, and low-dose total-body irradiation (TBI) followed by donor peripheral blood stem cell transplant (PBSCT) works in treating patients with hematologic malignancies. Giving chemotherapy drugs such as fludarabine phosphate and melphalan, and low-dose TBI before a donor PBSCT helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from the donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cell from a donor can make an immune response against the body's normal cells. Giving tacrolimus, mycophenolate mofetil (MMF), and methotrexate after 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
94

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Feb 2012

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

First Submitted

Initial submission to the registry

February 6, 2012

Completed
3 days until next milestone

First Posted

Study publicly available on registry

February 9, 2012

Completed
19 days until next milestone

Study Start

First participant enrolled

February 28, 2012

Completed
3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 28, 2015

Completed
2.1 years until next milestone

Results Posted

Study results publicly available

July 2, 2017

Completed
2.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

August 29, 2019

Completed
Last Updated

September 24, 2019

Status Verified

September 1, 2019

Enrollment Period

3.2 years

First QC Date

February 6, 2012

Results QC Date

June 30, 2017

Last Update Submit

September 16, 2019

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 Grade III Lymphomatoid GranulomatosisAdult Nasal Type Extranodal NK/T-cell LymphomaAnaplastic Large Cell LymphomaAngioimmunoblastic T-cell LymphomaAplastic AnemiaBurkitt LymphomaChildhood Acute Lymphoblastic Leukemia in RemissionChildhood Acute Myeloid Leukemia in RemissionChildhood Chronic Myelogenous LeukemiaChildhood Diffuse Large Cell LymphomaChildhood Grade III Lymphomatoid GranulomatosisChildhood Immunoblastic Large Cell LymphomaChildhood Myelodysplastic SyndromesChildhood Nasal Type Extranodal NK/T-cell LymphomaChronic Myelomonocytic LeukemiaChronic Phase Chronic Myelogenous LeukemiaCongenital Amegakaryocytic ThrombocytopeniaDiamond-Blackfan AnemiaExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissueHepatosplenic T-cell LymphomaJuvenile Myelomonocytic LeukemiaMyelodysplastic/Myeloproliferative Neoplasm, UnclassifiableNodal Marginal Zone B-cell LymphomaParoxysmal Nocturnal HemoglobinuriaPeripheral T-cell LymphomaPolycythemia VeraPost-transplant Lymphoproliferative DisorderPreviously Treated Myelodysplastic SyndromesPrimary MyelofibrosisRecurrent 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 Childhood Acute Lymphoblastic LeukemiaRecurrent Childhood Acute Myeloid LeukemiaRecurrent 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 Hairy Cell LeukemiaRefractory Multiple MyelomaSecondary Acute Myeloid LeukemiaSecondary Myelodysplastic SyndromesSecondary MyelofibrosisSevere Combined ImmunodeficiencySevere Congenital NeutropeniaShwachman-Diamond SyndromeSplenic Marginal Zone LymphomaT-cell Large Granular Lymphocyte LeukemiaWaldenstrom MacroglobulinemiaWiskott-Aldrich Syndrome

Outcome Measures

Primary Outcomes (1)

  • Transplant Related Mortality (TRM)

    Day 100 transplant related mortality (TRM). An exact 95% confidence interval will be provided.

    In the first 100 days from day 0 of transplant

Secondary Outcomes (3)

  • Clinical Response

    In the first 100 days from day 0 of transplant

  • Progression Free Survival (PFS) at One Year

    day of transplant until progression up to 5 years

  • Median Time to Neutrophil Engraftment

    Day 100

Study Arms (1)

Treatment (reduced intensity allogeneic PBSCT)

EXPERIMENTAL

PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan IV over 30 minutes on day -2. Patients undergo low-dose TBI BID on day -1. TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0. GvHD PROPHYLAXIS: Patients receive tacrolimus IV or PO BID on days -1 to 100 with taper over 4-6 months, MMF PO or IV every 6-8 hours on days -1 to 60, and methotrexate IV over 15 to 30 minutes on days 1, 3, and 6.

Drug: fludarabine phosphateDrug: melphalanRadiation: total-body irradiationDrug: tacrolimusDrug: mycophenolate mofetilDrug: methotrexateOther: laboratory biomarker analysisProcedure: allogeneic hematopoietic stem cell transplantationProcedure: peripheral blood stem cell transplantation

Interventions

fludarabine phosphateDRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, Fludara
Treatment (reduced intensity allogeneic PBSCT)
melphalanDRUG

Given IV

Also known as: Alkeran, CB-3025, L-PAM, L-phenylalanine mustard, L-Sarcolysin
Treatment (reduced intensity allogeneic PBSCT)
total-body irradiationRADIATION

Undergo TBI

Also known as: TBI
Treatment (reduced intensity allogeneic PBSCT)
tacrolimusDRUG

Given IV or PO

Also known as: FK 506, Prograf
Treatment (reduced intensity allogeneic PBSCT)
mycophenolate mofetilDRUG

Given IV or PO

Also known as: Cellcept, MMF
Treatment (reduced intensity allogeneic PBSCT)
methotrexateDRUG

Given IV

Also known as: amethopterin, Folex, methylaminopterin, Mexate, MTX
Treatment (reduced intensity allogeneic PBSCT)
laboratory biomarker analysisOTHER

Correlative studies

Treatment (reduced intensity allogeneic PBSCT)
allogeneic hematopoietic stem cell transplantationPROCEDURE

Undergo allogeneic PBSCT

Treatment (reduced intensity allogeneic PBSCT)
peripheral blood stem cell transplantationPROCEDURE

Undergo PBSCT

Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell
Treatment (reduced intensity allogeneic PBSCT)

Eligibility Criteria

Age3 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Diagnosis of a histology documented hematologic malignancy or marrow disorder
  • BONE MARROW FAILURE DISORDERS:
  • Acquired bone marrow failure disorders include aplastic anemia, paroxysmal nocturnal hemoglobinuria (PNH) \* Primary allogeneic HSCT is appropriate for selected patients with severe aplastic anemia; however, patients with aplastic anemia must have failed at least one cycle of standard immunosuppressive therapy with calcineurin inhibitor plus anti-thymocyte globulin (ATG) if a fully matched donor is available \* Patients with PNH should not be eligible for a myeloablative HSCT
  • Hereditary bone marrow failure disorders include Diamond-Blackfan Anemia, Shwachman-Diamond Syndrome, Kostmann Syndrome, congenital Amegakaryocytic Thrombocytopenia; Fanconi Anemia or related chromosomal breakage syndrome, Dyskeratosis Congenital are excluded from this study die to their poor deoxyribonucleic acid (DNA) repair capacity \* Fanconi anemia or related chromosomal breakage syndrome: positive chromosome breakage analysis using diepoxybutane (DEB) or mitomycin C if applicable \* Dyskeratosis Congenita: diagnosis is supported by using either telomerase RNA component (TERC) gene mutation in autosomal dominant Dyskeratosis Congenita or X-linked DKC1 gene mutation
  • Other non-malignant hematologic or immunologic disorders that require transplantation \* Quantitative or qualitative congenital platelet disorders (including but not limited to congenital amegakaryocytopenia, absent-radii syndrome, Glanzmann's thrombasthenia) \* Quantitative or qualitative congenital neutrophil disorders (including but not limited to chronic granulomatous disease, congenital neutropenia) \*Congenital primary immunodeficiency syndrome, Wiskott-Aldrich syndrome, CD40 ligand deficiency, T-cell deficiencies)
  • ACUTE LEUKEMIAS:
  • Subjects must be ineligible for or unable to receive a conventional myeloablative transplantation
  • Resistant or recurrent disease after at least one standard combination chemotherapy OR first remission patients at high risk of relapse \* Acute myeloid leukemia (AML)
  • antecedent myelodysplastic syndrome, secondary AML, high risk cytogenetic abnormalities or normal cytogenetics with high-risk molecular mutations (e.g., fms-like tyrosine kinase3-internal tandem duplication \[Flt3-ITD\] mutation) \* Acute lymphocytic leukemia (ALL)
  • high or standard risk ALL
  • CHRONIC MYELOID LEUKEMIA (CML):
  • Chronic phase (intolerant or unresponsive to imatinib and/or other tyrosine kinase inhibitors), second chronic phase or accelerated phase who are ineligible for conventional myeloablative transplantation
  • MYELOPROLIFERATIVE AND MYELODYSPLASTIC SYNDROME (MDS):
  • Myelofibrosis (with/without splenectomy) with intermediate to high risk features
  • Advanced polycythemia vera nor responding to standard therapy
  • +29 more criteria

You may not qualify if:

  • Uncontrolled central nervous system (CNS) disease (for hematologic malignancies)
  • Karnofsky (adult) or Lansky (for =\< 16 years) performance status \< 50%
  • Diffusing capacity of the lung for carbon monoxide (DLCO) \< 40% predicted, corrected for hemoglobin and/or alveolar ventilation
  • Left ventricular ejection fraction \< 40% - Bilirubin \>= 3 X upper limit of normal
  • Liver alkaline phosphatase \>= 3 x upper limit of normal
  • Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvate transaminase (SGPT) \>= 3 x upper limit of normal
  • Child's class B and C liver failure
  • Calculated creatinine clearance \< 40 cc/min by the modified Cockroft-Gault formula for adults or the Schwartz formula for pediatrics
  • Patients who have received maximally allowed doses (given in 2 Gy fractionations, or equivalent) of previous radiation therapy to various organs as follows: \* Mediastinum: adult -40, pediatric (=\<18 yrs) - 21 \* Heart: adult 36, pediatric - 26 \* Whole lung(s): adult - 12, pediatric - 10 \* Small bowel: adult - 46, pediatric - 40 \* Kidneys: adult - 12, pediatric - 10 \* Whole liver: adult - 20, pediatric - 20 \* Spinal cord: adult - 36, pediatric - 36 \* Whole Brain: adult 30, pediatric - 30
  • Patients who previously have received a higher than allowed dose of radiation to a small lung, liver, and brain volume, will be evaluated by the radiation oncologist to determine if the patient is eligible for study
  • Uncontrolled diabetes mellitus, cardiovascular disease, active serious infection or other condition which, in the opinion of treating physician, would make this protocol unreasonably hazardous for the patient
  • Human immunodeficiency virus (HIV) positive
  • Patients who in the opinion of the treating physician are unlikely to comply with the restrictions of allogeneic stem cell transplantation based on formal psychosocial screening
  • Female of childbearing potential with a positive pregnancy test

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Accelerated PhaseCongenital AbnormalitiesLymphoma, Extranodal NK-T-CellLymphoma, Large-Cell, AnaplasticImmunoblastic LymphadenopathyAnemia, AplasticBurkitt LymphomaLymphoma, Large B-Cell, DiffuseLeukemia, Myelomonocytic, ChronicLeukemia, Myeloid, Chronic-PhaseCongenital amegakaryocytic thrombocytopeniaAnemia, Diamond-BlackfanLeukemia, Myelomonocytic, JuvenileMyeloproliferative DisordersLymphoma, B-Cell, Marginal ZoneHemoglobinuria, ParoxysmalLymphoma, T-Cell, PeripheralPolycythemia VeraPrimary MyelofibrosisPrecursor Cell Lymphoblastic Leukemia-LymphomaLeukemia, Myeloid, AcuteLymphoma, Non-HodgkinHodgkin DiseaseLymphoma, Large-Cell, ImmunoblasticPrecursor T-Cell Lymphoblastic Leukemia-LymphomaDendritic Cell Sarcoma, InterdigitatingLymphoma, T-Cell, CutaneousLymphoma, FollicularLymphoma, Mantle-CellMycosis FungoidesSezary SyndromeLeukemia, Lymphocytic, Chronic, B-CellRecurrenceLeukemia, Hairy CellMultiple MyelomaSevere Combined ImmunodeficiencyNeutropenia, Severe Congenital, Autosomal Recessive 3Shwachman-Diamond SyndromeLeukemia, Large Granular LymphocyticWaldenstrom MacroglobulinemiaWiskott-Aldrich Syndrome

Interventions

fludarabine phosphateMelphalanWhole-Body IrradiationTacrolimusMycophenolic AcidMethotrexatemerphosPeripheral 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 DiseasesLymphadenopathyAnemiaBone Marrow Failure DisordersEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLymphoma, B-CellMyelodysplastic-Myeloproliferative DiseasesAnemia, Hypoplastic, CongenitalRed-Cell Aplasia, PureCongenital Bone Marrow Failure SyndromesGenetic Diseases, InbornAnemia, HemolyticMyelodysplastic SyndromesBone Marrow NeoplasmsHematologic NeoplasmsNeoplasms by SiteLeukemia, LymphoidHistiocytic Disorders, MalignantHistiocytosisLeukemia, B-CellNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersPrimary Immunodeficiency DiseasesInfant, Newborn, DiseasesDNA Repair-Deficiency DisordersMetabolic DiseasesNutritional and Metabolic DiseasesImmunologic Deficiency SyndromesExocrine Pancreatic InsufficiencyPancreatic DiseasesDigestive System DiseasesLipid Metabolism, Inborn ErrorsLipid Metabolism DisordersLipomatosisLeukemia, T-CellBlood Coagulation Disorders, InheritedBlood Coagulation DisordersLymphopeniaLeukopeniaCytopeniaLeukocyte DisordersGenetic Diseases, X-Linked

Intervention Hierarchy (Ancestors)

Nitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhenylalanineAmino Acids, AromaticAmino Acids, CyclicAmino AcidsAmino Acids, Peptides, and ProteinsRadiotherapyTherapeuticsInvestigative TechniquesMacrolidesLactonesCaproatesAcids, AcyclicCarboxylic AcidsFatty AcidsLipidsAminopterinPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsHematopoietic Stem Cell TransplantationStem Cell TransplantationCell TransplantationCell- and Tissue-Based TherapyBiological TherapyTransplantationSurgical Procedures, Operative

Results Point of Contact

Title
Senior Administrator, Compliance - Clinical Research Services
Organization
Roswell Park Cancer Institute
716-845-2300

Study Officials

  • George Chen

    Roswell Park Cancer Institute

    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 6, 2012

First Posted

February 9, 2012

Study Start

February 28, 2012

Primary Completion

May 28, 2015

Study Completion

August 29, 2019

Last Updated

September 24, 2019

Results First Posted

July 2, 2017

Record last verified: 2019-09

Locations

US(1)