NCT00856388

Brief Summary

This clinical trial is studying how well giving fludarabine phosphate and melphalan together with total-body irradiation followed by donor stem cell transplant works in treating patients with hematologic cancer or bone marrow failure disorders. Giving low doses of chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells or abnormal cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer or abnormal cells (graft-versus-tumor effect)

Trial Health

87
On Track

Trial Health Score

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

Enrollment
62

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started Jan 2009

Longer than P75 for not_applicable

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 14, 2009

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

March 4, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

March 5, 2009

Completed
3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 9, 2012

Completed
3.8 years until next milestone

Results Posted

Study results publicly available

June 13, 2016

Completed
2.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 13, 2019

Completed
Last Updated

November 13, 2019

Status Verified

October 1, 2019

Enrollment Period

3.6 years

First QC Date

March 4, 2009

Results QC Date

May 5, 2016

Last Update Submit

October 30, 2019

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 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 LymphomaAplastic AnemiaAtypical Chronic Myeloid Leukemia, BCR-ABL1 NegativeChildhood Acute Lymphoblastic Leukemia in RemissionChildhood Acute Myeloid Leukemia in RemissionChildhood Chronic Myelogenous LeukemiaChildhood Diffuse Large Cell LymphomaChildhood Immunoblastic Large Cell LymphomaChildhood Myelodysplastic SyndromesChildhood Nasal Type Extranodal NK/T-cell LymphomaChronic Eosinophilic LeukemiaChronic Myelomonocytic LeukemiaChronic Neutrophilic LeukemiaChronic Phase Chronic Myelogenous Leukemiade Novo Myelodysplastic SyndromesExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissueFanconi AnemiaJuvenile Myelomonocytic LeukemiaMyelodysplastic/Myeloproliferative Neoplasm, UnclassifiableNodal Marginal Zone B-cell 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 LymphomaParoxysmal Nocturnal HemoglobinuriaPreviously 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 Multiple MyelomaRelapsing Chronic Myelogenous LeukemiaSecondary Acute Myeloid LeukemiaSecondary Myelodysplastic SyndromesSplenic Marginal Zone 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 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 LymphomaWaldenström Macroglobulinemia

Outcome Measures

Primary Outcomes (1)

  • Day 100 TRM

    Day 100 Treatment Related Mortality An exact 95% confidence interval will be provided.

    First 100 days

Secondary Outcomes (7)

  • Median Time to ANC Engraftment

    Days 30

  • Median Time to Platelet Engraftment

    Day 100

  • Rate of Complete Donor Chimerism - Blood

    Day 30

  • Rate of Complete Donor Chimerism - Blood

    Day 100

  • Acute GVHD Grade III-IV

    Up to day 100

  • +2 more secondary outcomes

Study Arms (1)

Treatment (Reduced intensity allogeneic stem cell transplant)

EXPERIMENTAL

Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan\* IV over 30 minutes on day -2. Patients then undergo total-body irradiation on day -1 and allogeneic stem cell transplantation on day 0. Note: \*Patients with chromosomal breakage syndromes, such as Fanconi anemia or dyskeratosis congenita, receive anti-thymocyte globulin IV over 4 hours on day -4 to -2 instead of melphalan.

Drug: fludarabine phosphateDrug: melphalanRadiation: total-body irradiationProcedure: allogeneic hematopoietic stem cell transplantationBiological: anti-thymocyte globulin

Interventions

fludarabine phosphateDRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, Fludara
Treatment (Reduced intensity allogeneic stem cell transplant)
melphalanDRUG

Given IV

Also known as: Alkeran, CB-3025, L-PAM, L-phenylalanine mustard, L-Sarcolysin
Treatment (Reduced intensity allogeneic stem cell transplant)
total-body irradiationRADIATION

Undergo total-body irradiation

Also known as: TBI
Treatment (Reduced intensity allogeneic stem cell transplant)
allogeneic hematopoietic stem cell transplantationPROCEDURE

Undergo allogeneic stem cell transplantation

Treatment (Reduced intensity allogeneic stem cell transplant)
anti-thymocyte globulinBIOLOGICAL

Given IV

Also known as: ATG, ATGAM, lymphocyte immune globulin, Thymoglobulin
Treatment (Reduced intensity allogeneic stem cell transplant)

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 and other non-malignant hematologic or immunologic disorders:
  • Acquired bone marrow failure disorders include aplastic anemia, paroxysmal nocturnal hemoglobinuria (PNH):
  • Primary allogeneic hematopoietic stem cell transplantation (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 not available
  • Patients with PNH must have a history of thrombosis related to PNH
  • Hereditary bone marrow failure disorders include Fanconi anemia or related chromosomal breakage syndrome dyskeratosis congenita, Diamond-Blackfan anemia, Shwachman-Diamond syndrome, Kostmann syndrome, congenital amegakaryocytic thrombocytopenia:
  • Fanconi anemia or related chromosomal breakage syndrome: positive chromosome breakage analysis using diepoxybutane (DEB) or mitomycin C if applicable
  • Dyskeratosis: diagnosis is supported by using either telomerase reverse transcriptase (TERC) gene mutation in autosomal dominant Dyskeratosis Congenita or Xlinked 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 immunodeficiencies (including but not limited to Severe Combined Immunodeficiency Syndrome, Wiskott-Aldrick syndrome, CD40 ligand deficiency, T-cell deficiencies)
  • Acute leukemias:
  • Subjects must be ineligible for conventional myeloablative transplantation;
  • Resistant or recurrent disease after at least one standard combination chemotherapy regime or first remission patients at high risk of relapse OR First remission patients at high risk of relapse:
  • +39 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) less than 40% predicted, corrected for hemoglobin (Hb) and/or alveolar ventilation
  • Cardiac: left ventricular ejection fraction less than 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 Cockcroft-Gault formula for adults or the Schwartz formula for pediatrics
  • Patients who have received maximally allowed doses (given in 2 Gy fractions, or equivalent) of previous radiation therapy to various organs as follows:
  • Mediastinum 40 Gy
  • Heart (any volume) 36 Gy
  • Whole lungs 12 Gy
  • Small bowel (any volume) 46 Gy
  • Kidneys 12 Gy
  • +7 more criteria

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, AplasticLeukemia, Myeloid, Chronic, Atypical, BCR-ABL NegativeLymphoma, Large B-Cell, DiffusePdgfra-Associated Chronic Eosinophilic LeukemiaLeukemia, Myelomonocytic, ChronicLeukemia, Neutrophilic, ChronicLeukemia, Myeloid, Chronic-PhaseFanconi AnemiaLeukemia, Myelomonocytic, JuvenileMyeloproliferative DisordersLymphoma, B-Cell, Marginal ZoneHemoglobinuria, ParoxysmalPrimary MyelofibrosisPrecursor Cell Lymphoblastic Leukemia-LymphomaLeukemia, Myeloid, AcuteBurkitt LymphomaLymphoma, 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-CellRecurrenceMultiple MyelomaWaldenstrom Macroglobulinemia

Interventions

fludarabine phosphateMelphalanWhole-Body IrradiationAntilymphocyte Serumthymoglobulin

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 DisordersMyelodysplastic-Myeloproliferative DiseasesLymphoma, B-CellAnemia, Hypoplastic, CongenitalCongenital Bone Marrow Failure SyndromesGenetic Diseases, InbornDNA Repair-Deficiency DisordersMetabolic DiseasesNutritional and Metabolic DiseasesAnemia, HemolyticMyelodysplastic SyndromesLeukemia, LymphoidEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsHistiocytic Disorders, MalignantHistiocytosisLeukemia, B-CellNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Nitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhenylalanineAmino Acids, AromaticAmino Acids, CyclicAmino AcidsAmino Acids, Peptides, and ProteinsRadiotherapyTherapeuticsInvestigative TechniquesImmune SeraAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsSerum GlobulinsGlobulinsBiological ProductsComplex Mixtures

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
not applicable
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 4, 2009

First Posted

March 5, 2009

Study Start

January 14, 2009

Primary Completion

August 9, 2012

Study Completion

March 13, 2019

Last Updated

November 13, 2019

Results First Posted

June 13, 2016

Record last verified: 2019-10

Locations

US(1)