- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT02638467
Allogeneic Stem Cell Transplantation in Chronic Myeloid Leukemia Failing TKIs Therapy
Allogeneic Haematopoietic Stem Cell Transplantation From a Matched Donor in Patients With Chronic Myeloid Leukemia Failing to Gain Normal Hemopoiesis Under TKIs Therapy
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Studietype
Registrering (Faktiske)
Fase
- Fase 2
Kontakter og plasseringer
Studiesteder
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Italy/MB
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Monza, Italy/MB, Italia, 20900
- Asst-Monza
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MI
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Milano, MI, Italia, 20132
- Ospedale San Raffaele
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-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
Inclusion Criteria:
- Chronic Myeloid Leukaemia -CML- in chronic phase (CP)
- Failure to achieve at least a Major Cytogenetic Response (MCyR) after a minimum of 18 months of TKIs treatment
- Inability to tolerate 3 months of uninterrupted full dose TKIs therapy due to hematological toxicity
- A minimum of three treatment interruptions due to hematological toxicity Availability of a HLA-identical related donor (Matched Related Donor, MRD)
- Availability of unrelated donor (Matched Unrelated Donor, MUD) satisfying the criteria of a 10/10 antigen match at (Human Leukocyte Antigen) HLA-A, -B, -C and - DRB1, -DQB1 at high resolution typing, or 9/10 with a permissive - DP disparity according to Fleischhauer model (Crocchiolo et al, Blood 2009)
- Target graft size (bone marrow):
- bone marrow: > 3 x 106 CD34+ cells/kg BW recipient or > 3 x 108 nucleated cells/kg BW
- Karnofsky Index > 80 %
- Age ≥18 and ≤70 years
- Adequate contraception in female patients of child-bearing potential
- Written informed consent
Exclusion Criteria:
- Secondary malignancies
- A hematopoietic cell transplantation-specific comorbidity index (Sorror et al Appendix C) > 4
- Known and manifested malignant involvement of the Central Nervous System (CNS)
- Active infectious disease
- Active human immunodeficiency virus (HIV), Hepatitis B virus (HBV) or Hepatitis B virus (HCV) infection
- Impaired liver function (Bilirubin > upper normal limit; Transaminases > 3.0 x upper normal limit)
- Impaired renal function (Creatinine-clearance < 60 ml/min; Serum Creatinine > 1.5 x upper normal limit).
- Pleural effusion or ascites > 1.0 L
- Pregnancy or lactation
- Known hypersensitivity to Busilvex and/or fludarabine 11 Non-co-operative behaviour or non-compliance 12 Psychiatric diseases or conditions that might impair the ability to give informed consent
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
---|---|
Eksperimentell: Bosutinib and Bone Marrow Transplant
Subjects will receive 400mg of bosutinib from day at least -45 to day -15 to assess the sensitivity of patient Chronic Myeloid Leukemia (CML) to this TKI.
Patients will be transplanted with the aim to transplant > 3 x 106 CD34+ cells/kg Body Weight (BW) recipient from bone marrow or > 3 x 108 nucleated cells/kg BW recipient from bone marrow.
Then, subjects will receive 400mg of bosutinib once daily from day +30 after transplant.
|
Subjects will receive 400mg of bosutinib once daily from day +30 after transplant, by mouth with food, preferably in the morning.
Bosutinib will also be administered from day at least -45 to day -15 to assess the sensitivity of patient CML to this TKI.
Andre navn:
Samples of the unrelated stem cell graft shall be characterised with respect to the number of CD34 positive cells per kg body weight of the recipient. The number of transplanted CD34 positive cells per kg body weight (BW) of the recipient shall be recorded in the Case Report Form (CRF). If the transplant was cryopreserved the number of viable CD34 positive cells has to be determined after thawing and documented. The goal is to transplant > 3 x 106 CD34+ cells/kg BW recipient from bone marrow or > 3 x 108 nucleated cells/kg BW recipient from bone marrow |
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
---|---|---|
Efficacy as assessed by the percentage of patients with Complete Cytogenetic Response (CCyR)
Tidsramme: 12 months
|
The percentage of patients with Complete Cytogenetic Response (CCyR) will be calculated as the complement to the percentage of failures on the total number of patients treated, where failure includes the following events: no engraftment, death within 12 months, no CCyR at 12 months.
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12 months
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
---|---|---|
Samlet overlevelse
Tidsramme: 12 måneder
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12 måneder
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|
Percentage of patients with engraftment
Tidsramme: 12 months
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12 months
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percentage of patients with complete chimerism (95%)
Tidsramme: Day +28, +56 and +100
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Day +28, +56 and +100
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Evaluation of Major Cytogenetic Response (MCyR)
Tidsramme: 12 months
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Major Cytogenetic Response (MCyR) is < 36% Ph+ metaphases
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12 months
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Evaluation of molecular responses
Tidsramme: 12 months
|
Molecular response is defined
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12 months
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Relapse incidence (RI)
Tidsramme: 12 months
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12 months
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Incidence of non-relapse mortality (NRM)
Tidsramme: Within day +28 and +360
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Within day +28 and +360
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Incidence and severity of acute and chronic graft vs. host disease (GvHD)
Tidsramme: 12 months
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12 months
|
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Quality of Life (QoL)
Tidsramme: 12 months
|
Evaluation of QoL with EQ-5D-5L (Italian - Version 2) and FACT-Leu (Italian -Version 4)
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12 months
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Overall Survival (OS)
Tidsramme: 36 months
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2 years after transplantation of the last patient included (this is intended to allow evaluations of all expected major molecular responses)
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36 months
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Progression Free Survival (PFS)
Tidsramme: 36 months
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2 years after transplantation of the last patient included (this is intended to allow evaluations of all expected major molecular responses)
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36 months
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Relapse Incidence (RI)
Tidsramme: 36 months
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2 years after transplantation of the last patient included (this is intended to allow evaluations of all expected major molecular responses)
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36 months
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Chronic Graft-versus-host Disease (cGvHD)
Tidsramme: 36 months
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2 years after transplantation of the last patient included (this is intended to allow evaluations of all expected major molecular responses)
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36 months
|
Samarbeidspartnere og etterforskere
Sponsor
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: CARLO GAMBACORTI-PASSERINI, MD, University of Milano Bicocca
Publikasjoner og nyttige lenker
Generelle publikasjoner
- Redaelli A, Bell C, Casagrande J, Stephens J, Botteman M, Laskin B, Pashos C. Clinical and epidemiologic burden of chronic myelogenous leukemia. Expert Rev Anticancer Ther. 2004 Feb;4(1):85-96. doi: 10.1586/14737140.4.1.85.
- Heisterkamp N, Stephenson JR, Groffen J, Hansen PF, de Klein A, Bartram CR, Grosveld G. Localization of the c-ab1 oncogene adjacent to a translocation break point in chronic myelocytic leukaemia. Nature. 1983 Nov 17-23;306(5940):239-42. doi: 10.1038/306239a0.
Hjelpsomme linker
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- alloCML
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