- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT00027560
Melphalan, Fludarabine, and Alemtuzumab Followed by Peripheral Stem Cell Transplant in Treating Patients With Hematologic Cancer
Phase II Trial Of Non-Myeloablative Regimen Combining Melphalan, Fludarabine, And Anti-CD52 Monoclonal Antibody (CAMPATH-1H) Followed By An Unmodified Hematopoietic Cell Transplant From An HLA Compatible Related Or Unrelated Donor For Treatment Of Lymphohematopoietic Malignancies
RATIONALE: Giving low doses of chemotherapy, such as melphalan and fludarabine, and a monoclonal antibody, such as alemtuzumab, before a donor bone marrow or peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system 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 cyclosporine after the transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well fludarabine, melphalan, alemtuzumab, and peripheral stem cell transplant work in treating patients with hematologic cancer.
Studieoversigt
Status
Betingelser
Detaljeret beskrivelse
OBJECTIVES:
Overall survival-12 months
Overall survival-24 months
Acute Graft-versus-Host Disease Matched Related patients-up to 4 months post transplant
Acute Graft-versus-Host Disease Unrelated and Mismatched related patients- up to 4 months post transplant
Chronic Graft-versus-Host Disease Matched Related patients- up to 2 years post transplant
Chronic Graft-versus-host disease Unrelated and Mismatched related patients- up to 2 years post transplant
- OUTLINE: Patients are stratified according to donor type (HLA-matched related vs HLA-matched unrelated, single HLA-allele disparate related, or unmatched) (HLA-mismatched related or matched unrelated donor stratum closed to accrual as of 1/11/06).
Patients receive a nonmyeloablative regimen comprising alemtuzumab IV over 8 hours on days -8 to -5, fludarabine IV over 30 minutes on days -8 to -4, and melphalan IV over 30 minutes on days -3 and -2. Allogeneic peripheral blood stem cells or bone marrow is infused on day 0.
Patients receive graft-versus host disease prophylaxis comprising cyclosporine IV every 12 hours beginning on day -1 and continuing orally as tolerated until day 100.
Patients are followed every 6 weeks for 6 months, every 3 months for 6 months, every 3-6 months for 1 year, and then annually thereafter or as clinically indicated.
PROJECTED ACCRUAL: A maximum of 50 patients (25 HLA-matched related and 25 HLA-mismatched related or matched unrelated) will be accrued for this study within 2 years (HLA-mismatched related or matched unrelated donor stratum closed to accrual as of 1/11/06).
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 2
Kontakter og lokationer
Studiesteder
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New York
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New York, New York, Forenede Stater, 10021
- Memorial Sloan-Kettering Cancer Center
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
INCLUSION CRITERIA:
- Disease criteria: This trial is primarily designed for: 1) patients with relapsed or primary refractory non-Hodgkin's lymphoma, 2) chemosensitive relapsed or refractory acute and chronic lymphocytic leukemias, 3) relapsed or primary refractory Hodgkin's Disease, or advanced (Durie-Salmon stage II or III) multiple myeloma, advanced Waldenstrom macroglobulinemia, who, by virtue of advanced age, intensity of prior radiation and/or chemotherapy, history of prior toxicity associated with chemo/radiotherapy or existing organ dysfunction, would be at undue risk of regimen associated mortality if transplanted according to protocols involving myeloablative conditioning regimens.
- Patients with aggressive NHL histologies must have chemo/radiosensitive disease, or have non-progressive disease, or have stable disease on therapy, and be ineligible for an autologous HSC transplant because of disease in the marrow.
- Patients with chronic myeloid leukemia and high risk forms of acute myelogenous leukemia or myelodysplastic syndromes are also eligible in the absence of an alternative active higher priority allogeneic transplant protocol for which they are eligible.
- Age criteria: Patients may be up to 70 years of age. There is no lower age threshold. Patients above the age of 70 may also participate, after evaluation and approval by the BMT Service attendings.
- Absence of active or uncontrolled bacterial, viral, or fungal infection that would contraindicate the use of myelosuppressive chemotherapy.
- Patients must have a healthy HLA-compatible donor, either a matched or single HLA allele disparate related donor or a similarly compatible unrelated donor recruited through the National Marrow Donor Program. Related donors must be willing to participate as research subjects and be willing to receive G-CSF to mobilize PBPC and undergo leukapheresis to donate PBSC. Unrelated donors identified by the NMDP may elect to donate either PBSC after treatment with G-CSF, or bone marrow. These unrelated donors will provide informed consent and their PBSC or bone marrow donations will be obtained at a qualified donor center participating in the NMDP.
- Each patient must be willing to participate as a research subject and must sign an informed consent form after discussion of the nature and risks of the study prior to entering the protocol. Parents or legal guardians of patients who are minors will sign the consent form for these patients after discussion of the nature and risks of the study.
EXCLUSION CRITERIA:
- Female patients who are pregnant or lactating.
- Active or uncontrolled viral (including HIV-1), bacterial or fungal infection.
- Severe renal insufficiency (creatinine >2.0 or creatinine clearance < 30mL/minute)
- Severe hepatic dysfunction, as defined by: total bilirubin greater than 2.5 mg/dL and AST and ALT >3xnl, unless the liver is involved with disease.
- Severe cardiac insufficiency, defined as a resting left ventricular ejection of less than 30% as measured by echocardiography or radionuclide cardiac angiography. Patients on cardiac medications for congestive heart failure are eligible, as long as their LVEF is greater than 30% on medication.
- Severe pulmonary insufficiency, as defined by an adjusted diffusing capacity of less than 40% of predicted value.
- Karnofsky or Lansky score <40%
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: TREATMENT OF LYMPHOHEMATOPOIETIC MALIGNANCIES
This is a stratified single-armed phase II study designed to investigate the safety and efficacy of hematopoietic cell allografts administered after nonmyeloablative cytoreduction.
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Consenting individuals will receive pretransplant immunosuppressive cytoreduction, which will consist of 4 days of Campath-1H, 5 days of fludarabine, and two days of melphalan. All therapy should be completed approximately 24-36 hours before administration of the primary allograft. Campath-1H (20mg/dose/day) will be administered for each of four days from day -8 to day -5, inclusive. Each dose will be infused intravenously over 8 hours.
Andre navne:
Patients will be treated with Cyclosporine as prophylaxis against GvHD.
Cyclosporine will be initiated at least 1 day prior to transplant at a dose of 1.5 mg / kg IV q12h (3 mg / kg / day = total daily dose).
Dose will thereafter be adjusted to maintain a trough serum level of 200-300 ng /ml.
Cyclosporine will be administered intravenously until the patient tolerates full alimentation, at which time conversion to oral dosing to sustain therapeutic levels will be initiated according to standard BMT service guidelines.
Fludarabine, 25mg/m2/d will be administered for each of five days from day -8 to day -4, inclusive.
Each dose will be infused intravenously over 30 minutes.
Melphalan will be administered intravenously over 30 minutes on each of two days from day -3 to day -2, inclusive.
The dose for recipients of HLA-matched related grafts will be 50 mg/m2/day x 2. The dose for recipients of HLA-matched unrelated and HLA-single allele disparate related or unrelated marrow or PBSC transplants will be 70 mg/m2/day x 2.
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Overall Survival
Tidsramme: 12 months post transplant
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12 months post transplant
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Overall Survival
Tidsramme: 24 months post transplant
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24 months post transplant
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Acute Graft-versus-Host Disease Matched Related Patients
Tidsramme: up to 4 months post transplant
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Grade III-IV Acute Graft-versus-Host Disease
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up to 4 months post transplant
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Acute Graft-versus-Host Disease Unrelated and Mismatched Related Patients
Tidsramme: up to 4 months post transplant
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Grade III-IV Acute Graft-versus-Host Disease
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up to 4 months post transplant
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Extensive Chronic Graft-versus-Host Disease Matched Related Patients
Tidsramme: up to 2 years post transplant
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up to 2 years post transplant
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Extensive Chronic Graft-versus-Host Disease Unrelated and Mismatched Related Patients
Tidsramme: up to 2 years post transplant
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up to 2 years post transplant
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Samarbejdspartnere og efterforskere
Samarbejdspartnere
Efterforskere
- Studiestol: Hugo R. Castro-Malaspina, MD, Memorial Sloan Kettering Cancer Center
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
- tilbagevendende grad 3 follikulært lymfom
- tilbagevendende voksent diffust storcellet lymfom
- tilbagevendende voksen immunoblastisk storcellet lymfom
- recidiverende voksen Burkitt lymfom
- tilbagevendende små ikke-spaltede celle lymfomer i barndommen
- tilbagevendende storcellet lymfom i barndommen
- tidligere behandlede myelodysplastiske syndromer
- akut myeloid leukæmi hos voksne med 11q23 (MLL) abnormiteter
- kronisk myelogen leukæmi i barndommen
- barndoms myelodysplastiske syndromer
- tilbagevendende akut myeloid leukæmi hos voksne
- recidiverende voksen Hodgkin lymfom
- tilbagevendende/refraktær Hodgkin-lymfom i barndommen
- recidiverende voksent diffust små spaltet celle lymfom
- recidiverende voksent diffust blandet celle lymfom
- recidiverende kronisk myelogen leukæmi
- stadium II myelomatose
- stadium III myelomatose
- tilbagevendende grad 1 follikulært lymfom
- tilbagevendende grad 2 follikulært lymfom
- tilbagevendende marginal zone lymfom
- tilbagevendende lille lymfocytisk lymfom
- ekstranodal marginal zone B-celle lymfom af slimhinde-associeret lymfoid væv
- nodal marginal zone B-celle lymfom
- milt marginal zone lymfom
- tilbagevendende lymfoblastisk lymfom hos voksne
- tilbagevendende kappecellelymfom
- refraktær kronisk lymfatisk leukæmi
- refraktær myelomatose
- tilbagevendende akut lymfatisk leukæmi hos voksne
- Waldenström makroglobulinæmi
- tilbagevendende akut lymfatisk leukæmi hos børn
- tilbagevendende akut myeloid leukæmi i barndommen
- myelodysplastisk/myeloproliferativ neoplasma, uklassificerbar
- tilbagevendende lymfoblastisk lymfom i barndommen
- atypisk kronisk myeloid leukæmi, BCR-ABL1 negativ
Yderligere relevante MeSH-vilkår
- Patologiske processer
- Hjerte-kar-sygdomme
- Karsygdomme
- Sygdomme i immunsystemet
- Neoplasmer efter histologisk type
- Lymfoproliferative lidelser
- Lymfesygdomme
- Immunproliferative lidelser
- Sygdom
- Knoglemarvssygdomme
- Hæmatologiske sygdomme
- Hæmoragiske lidelser
- Hæmostatiske lidelser
- Paraproteinæmier
- Blodproteinforstyrrelser
- Forstadier til kræft
- Neoplasmer
- Lymfom
- Syndrom
- Myelodysplastiske syndromer
- Myelomatose
- Neoplasmer, Plasmacelle
- Leukæmi
- Præleukæmi
- Plasmacytom
- Myeloproliferative lidelser
- Myelodysplastisk-myeloproliferative sygdomme
- Lægemidlers fysiologiske virkninger
- Molekylære mekanismer for farmakologisk virkning
- Anti-infektionsmidler
- Enzymhæmmere
- Antirheumatiske midler
- Antimetabolitter, Antineoplastisk
- Antimetabolitter
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Antineoplastiske midler, Alkylering
- Alkyleringsmidler
- Myeloablative agonister
- Antineoplastiske midler, immunologiske
- Dermatologiske midler
- Antifungale midler
- Calcineurin-hæmmere
- Melphalan
- Fludarabin
- Fludarabin phosphat
- Cyclosporin
- Cyclosporiner
- Alemtuzumab
Andre undersøgelses-id-numre
- 01-092
- MSKCC-01092
- NCI-G01-2028
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .
Kliniske forsøg med allogen knoglemarvstransplantation
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Gruppo Italiano Trapianto di Midollo OsseoAfsluttet
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Ossium Health, Inc.Center for International Blood and Marrow Transplant ResearchRekrutteringAkut myeloid leukæmi | Akut lymfatisk leukæmi | Akut leukæmi | Akut udifferentieret leukæmi | Akut bifænotypisk leukæmiForenede Stater