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- Klinische proef NCT00376480
Laboratory-Treated Lymphocyte Infusion After Haploidentical Donor Stem Cell Transplant
Delayed Infusion of Ex Vivo Anergized Peripheral Blood Mononuclear Cells Following CD34 Selected Peripheral Blood Stem Cell Transplantation From a Haploidentical Donor for Patients With Acute Leukemia and Myelodysplasia
RATIONALE: Giving total-body irradiation and chemotherapy, such as thiotepa and fludarabine, before a donor stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a 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 cells from a donor can make an immune response against the body's normal cells. Giving methylprednisolone and antithymocyte globulin before transplant and peripheral blood cells that have been treated in the laboratory after transplant may stop this from happening.
PURPOSE: This phase I trial is studying the side effects and best dose of laboratory-treated peripheral blood cell infusion after donor stem cell transplant in treating patients with hematologic cancers or other diseases.
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
- Geneesmiddel: methylprednisolon
- Geneesmiddel: thiotepa
- Biologisch: anti-thymocyt globuline
- Geneesmiddel: fludarabinefosfaat
- Procedure: allogene hematopoëtische stamceltransplantatie
- Procedure: in vitro behandelde perifere bloedstamceltransplantatie
- Straling: totale lichaamsbestraling
- Biologisch: therapie met perifere bloedlymfocyten
Gedetailleerde beschrijving
OBJECTIVES:
Primary
- Establish the feasibility of delayed infusion of ex vivo anergized donor peripheral blood mononuclear cells (PBMC) after CD34 (cluster designation 34)-selected megadose haploidentical hematopoietic stem cell transplantation (HSCT) in patients with hematopoietic cancers or other diseases.
- Determine the feasibility of collecting parental allogeneic stimulator cells to induce anergy to the nonshared donor-recipient haplotype in these patients.
- Determine the feasibility of collecting donor PBMC as a source of T cells for ex vivo anergization.
- Determine the number of transplanted individuals who meet the criteria for proceeding to delayed infusion of ex vivo anergized donor PBMC.
- Establish the safety of delayed infusion of ex vivo anergized donor PBMC by establishing the maximum number of donor T cells that can be infused without unacceptable graft-versus-host disease.
Secondary
- Evaluate, in vitro, the induction and specificity of alloantigen hyporesponsiveness in donor PBMC after ex vivo anergization.
- Assess, in vitro, the function of immune cells engrafted in these patients.
- Assess, in vitro, whether alloantigen hyporesponsive donor T cells are present in these patients.
- Develop, preliminarily, in vitro data on the extent of pathogen-specific immunity and its rate of recovery.
- Describe the patterns of opportunistic infections in these patients.
OUTLINE: This is a multicenter, dose-escalation study of ex vivo anergized allogeneic peripheral blood mononuclear cells (PBMC). Patients who are treated on any dose level except dose level 1 are stratified according to age (under 17 [pediatric] vs 17 and over [adult]).
- Myeloablative conditioning regimen: Patients undergo total-body irradiation twice daily on days -11 to -9. Patients also receive thiotepa IV over 4 hours on days -8 and -7, fludarabine phosphate IV over 30 minutes on days -7 to -3, and anti-thymocyte globulin IV over 8 hours and methylprednisolone IV over 15-30 minutes on days -6 to -3.
- Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo CD34-selected PBSCT on day 0.
- Ex vivo anergized allogeneic PBMC infusion: If cells have engrafted and patients are free of active uncontrolled infection and graft-vs-host disease, patients undergo allogeneic or autologous PBMC infusion on day 35 or 42.
Cohorts of 3-8 patients receive escalating doses of ex vivo anergized allogeneic PBMCs until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 5 or 3 of 8 patients experience dose-limiting toxicity.
After completion of study, patients are followed periodically for 2 years.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 1
Contacten en locaties
Studie Locaties
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California
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Los Angeles, California, Verenigde Staten, 90027-0700
- Childrens Hospital Los Angeles
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Florida
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Gainesville, Florida, Verenigde Staten, 32610
- University of Florida Health Science Center - Gainesville
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Massachusetts
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Boston, Massachusetts, Verenigde Staten, 02114
- Massachusetts General Hospital
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Boston, Massachusetts, Verenigde Staten, 02115
- Children's Hospital Boston
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Boston, Massachusetts, Verenigde Staten, 02115
- Dana Farber Cancer Institute
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Texas
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Houston, Texas, Verenigde Staten, 77030-4009
- M. D. Anderson Cancer Center at University of Texas
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
DISEASE CHARACTERISTICS:
Diagnosis of 1 of the following:
Acute lymphocytic leukemia
In ≥ second complete remission (CR), defined as < 5% blasts in bone marrow (BM) and no active extramedullary disease OR in first CR with any of the following high risk features:
- History of induction failure
- Philadelphia chromosome positive
- t(4;11) by cytogenetic analysis
- Any infant with MLL rearrangements on cytogenetic analysis
- No relapse with isolated extramedullary disease after completion of prior treatment
Acute myeloid leukemia
- Failed induction therapy after < 3 courses
In ≥ second CR, defined as < 5% blasts in BM and no active extramedullary disease OR in first CR with any of the following high-risk features:
- History of induction failure = 5q- or monosomy 7 cytogenetic findings
Any of the following myelodysplastic syndromes:
- Refractory anemia (RA) with excess blasts (RAEB) with a high International Prognostic Scoring System (IPSS) score or score of intermediate-1(INT-1) or intermediate-2 (INT-2)
- RAEB in transformation with INT-1, INT-2, or high IPSS score
- RA with INT-2 score
Patients must have a healthy, related donor who is at least genotypically HLA-A, B, C, and DR haploidentical to the patient
- No suitably matched family donor defined by genotypic or phenotypic identity for ≥ 5/6 A, B, or DR loci
- No immediately available genotypically matched (6/6) unrelated marrow donor
- No immediately available umbilical cord blood donor with suitable cell dose after a search ≥ 2 months
- Patients whose medical condition is at high risk of deteriorating or whose disease is at high risk of progression during a donor search are eligible
- Has a parent with a haplotype that is disparate from that of the donor for the haplotype shared by the patient and parent, but not shared by the patient and donor OR patient is able to donate sufficient autologous cells by peripheral blood draw or unstimulated leukapheresis
- No active CNS disease
PATIENT CHARACTERISTICS:
- Room air O_2 saturation > 95% unless the lungs are involved with disease
- No clinical evidence of pulmonary insufficiency unless the lungs are involved with disease
- AST and ALT < 3 times upper limit of normal (ULN)*
- Bilirubin < 2.0 mg/dL*
- Creatinine < 2 times ULN OR creatinine clearance or glomerular filtration rate > 50% of the lower limit of normal
- LVEF > 45% OR shortening fraction > 20%
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No active infection, defined as absence of an infectious diagnosis or (in patients who have had a recent positive infectious diagnosis) the resolution of fever, documentation of negative cultures or antigen testing, continuation or completion of a course of appropriate therapy, and presence of stable to resolving clinical symptoms
- No evidence of HIV infection OR known HIV positivity NOTE: *Does not apply if liver is involved with disease
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior stem cell transplantation
- No other concurrent immunosuppressive therapy
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: NVT
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: administration of adoptive donor lymphocyte infusion
administration of donor lymphocytes made using costimulatory blockade ex vivo
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
---|---|---|
Feasibility of making and administering the adoptive T cell product
Tijdsspanne: from conditioning through administration of anergized cells on day 35-42
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ability to collect sufficient cells, make anergized product with good viability, without contamination and infuse per study toxicity of the conditioning regimen, the likelihood of engraftment, and the subsequent percentage of individuals who would be eligible to receive aDLI were determined.
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from conditioning through administration of anergized cells on day 35-42
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Safety of administering the adoptive T cell product on day 35-42 post haploidentical transplant
Tijdsspanne: the period from aDLI infusion through D100
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rates of graft failure with CD34 selected product, adverse and severe adverse reactions attributable to infusion of anergized donor cells, including fever, hypotension, acute graft vs host disease, organ dysfunction
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the period from aDLI infusion through D100
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Alloreactivity engendered by administering the adoptive T cell product
Tijdsspanne: from cell infusion through day 100
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occurrence and severity of acute GVHD
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from cell infusion through day 100
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
---|---|---|
Efficacy in restoring adaptive immunity
Tijdsspanne: from aDLI thorough 1 year
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incidence of viral infection and type of immune reconstitution by phenotype and function of T cells
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from aDLI thorough 1 year
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Medewerkers en onderzoekers
Sponsor
Medewerkers
Onderzoekers
- Studie stoel: Eva Guinan, MD, Dana-Farber Cancer Institute
Publicaties en nuttige links
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
- refractaire bloedarmoede
- vuurvaste bloedarmoede met overmatige ontploffing
- refractaire bloedarmoede met overmatige ontploffing in transformatie
- de novo myelodysplastische syndromen
- eerder behandelde myelodysplastische syndromen
- secundaire myelodysplastische syndromen
- volwassen acute myeloïde leukemie met 11q23 (MLL) afwijkingen
- volwassen acute myeloïde leukemie met inv(16)(p13;q22)
- volwassen acute myeloïde leukemie met t(15;17)(q22;q12)
- volwassen acute myeloïde leukemie met t(16;16)(p13;q22)
- volwassen acute myeloïde leukemie met t(8;21)(q22;q22)
- secundaire acute myeloïde leukemie
- acute lymfatische leukemie bij kinderen in remissie
- acute myeloïde leukemie bij kinderen in remissie
- myelodysplastische syndromen bij kinderen
- volwassen acute myeloïde leukemie in remissie
- volwassen acute lymfatische leukemie in remissie
Aanvullende relevante MeSH-voorwaarden
- Pathologische processen
- Neoplasmata per histologisch type
- Neoplasmata
- Ziekte
- Beenmergziekten
- Hematologische ziekten
- Voorstadia van kanker
- Syndroom
- Myelodysplastische syndromen
- Leukemie
- Preleukemie
- Fysiologische effecten van medicijnen
- Moleculaire mechanismen van farmacologische werking
- Autonome agenten
- Agenten van het perifere zenuwstelsel
- Ontstekingsremmende middelen
- Antimetabolieten, antineoplastische
- Antimetabolieten
- Antineoplastische middelen
- Immunosuppressieve middelen
- Immunologische factoren
- Anti-emetica
- Gastro-intestinale middelen
- Glucocorticoïden
- Hormonen
- Hormonen, hormoonvervangers en hormoonantagonisten
- Neuroprotectieve middelen
- Beschermende middelen
- Antineoplastische middelen, alkylering
- Alkyleringsmiddelen
- Myeloablatieve agonisten
- Methylprednisolon
- Fludarabine
- Fludarabine-fosfaat
- Thiotepa
- Antilymfocyten Serum
Andere studie-ID-nummers
- 05-030
- P30CA006516 (Subsidie/contract van de Amerikaanse NIH)
- P01CA100265 (Subsidie/contract van de Amerikaanse NIH)
- MDA-2005-0695
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
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Klinische onderzoeken op Myelodysplastische syndromen
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The Champ FoundationChildren's Hospital of Philadelphia; The Cleveland ClinicWervingPearson-syndroom | Single Large Scale Mitochondrial DNA Deletion Syndromes (SLSMDS)Verenigde Staten
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Assistance Publique - Hôpitaux de ParisVoltooidGezichtsverlammingFrankrijk
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Fred LublinPfizer; National Multiple Sclerosis SocietyBeëindigdMultiple scleroseVerenigde Staten
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Peking University People's HospitalBeijing HospitalOnbekendImmuun Trombocytopenie
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Assiut UniversityVoltooid
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University of Colorado, DenverUniversity of Pennsylvania; MallinckrodtBeëindigdMultiple scleroseVerenigde Staten
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Fundação de Medicina Tropical Dr. Heitor Vieira...VoltooidSARS-CoV-infectie | Ernstig acuut respiratoir syndroom (SARS) LongontstekingBrazilië
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Iran University of Medical SciencesIngetrokkenSchildklier oogziekteIran, Islamitische Republiek