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Trial record 97 of 1861 for:    "bone marrow" | Recruiting, Not yet recruiting Studies

Allogeneic Stem Cell Transplantation in Chronic Myeloid Leukemia Failing TKIs Therapy

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ClinicalTrials.gov Identifier: NCT02638467
Recruitment Status : Recruiting
First Posted : December 23, 2015
Last Update Posted : April 9, 2018
Sponsor:
Collaborator:
IRCCS San Raffaele
Information provided by (Responsible Party):
University of Milano Bicocca

Tracking Information
First Submitted Date  ICMJE December 9, 2015
First Posted Date  ICMJE December 23, 2015
Last Update Posted Date April 9, 2018
Actual Study Start Date  ICMJE November 2015
Estimated Primary Completion Date January 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 22, 2015)
Efficacy as assessed by the percentage of patients with Complete Cytogenetic Response (CCyR) [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 22, 2015)
  • Overall Survival [ Time Frame: 12 months ]
  • Percentage of patients with engraftment [ Time Frame: 12 months ]
  • percentage of patients with complete chimerism (95%) [ Time Frame: Day +28, +56 and +100 ]
  • Evaluation of Major Cytogenetic Response (MCyR) [ Time Frame: 12 months ]
    Major Cytogenetic Response (MCyR) is < 36% Ph+ metaphases
  • Evaluation of molecular responses [ Time Frame: 12 months ]
    Molecular response is defined
    • Complete: if there is undetectable BCR-ABL transcript
    • Major: if ratio BCR/ABL <= 0.1% on International Scale
  • Relapse incidence (RI) [ Time Frame: 12 months ]
  • Incidence of non-relapse mortality (NRM) [ Time Frame: Within day +28 and +360 ]
  • Incidence and severity of acute and chronic graft vs. host disease (GvHD) [ Time Frame: 12 months ]
  • Quality of Life (QoL) [ Time Frame: 12 months ]
    Evaluation of QoL with EQ-5D-5L (Italian - Version 2) and FACT-Leu (Italian -Version 4)
  • Overall Survival (OS) [ Time Frame: 36 months ]
    2 years after transplantation of the last patient included (this is intended to allow evaluations of all expected major molecular responses)
  • Progression Free Survival (PFS) [ Time Frame: 36 months ]
    2 years after transplantation of the last patient included (this is intended to allow evaluations of all expected major molecular responses)
  • Relapse Incidence (RI) [ Time Frame: 36 months ]
    2 years after transplantation of the last patient included (this is intended to allow evaluations of all expected major molecular responses)
  • Chronic Graft-versus-host Disease (cGvHD) [ Time Frame: 36 months ]
    2 years after transplantation of the last patient included (this is intended to allow evaluations of all expected major molecular responses)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Allogeneic Stem Cell Transplantation in Chronic Myeloid Leukemia Failing TKIs Therapy
Official Title  ICMJE Allogeneic Haematopoietic Stem Cell Transplantation From a Matched Donor in Patients With Chronic Myeloid Leukemia Failing to Gain Normal Hemopoiesis Under TKIs Therapy
Brief Summary Patients newly diagnosed with chronic phase chronic myeloid leukemia undergo treatment with TK inhibitors (TKI). A possible cause of TK failure is represented by the insufficient recovery of normal Ph- hematopoiesis during TKI treatment, with consequent severe cytopenias that limit TKI adequate administration. Although rare, this event happens in a proportion of 4-5% of CML patients. Our hypothesis is to circumvent this peculiar condition by providing a normal hematopoiesis from a HLA-matched donor (Human Leukocyte Antigen). The transplant procedure is therefore intended in providing a sustained hematopoiesis that will allow an early treatment with an adequate dosing of TKI. The transplant procedure planned in our study is built on all available evidences to provide the lowest incidence of acute and chronic GvHD (Graft-versus-host disease). Therefore, a bone marrow will be the preferential source and a GvHD prophylaxis based on Anti-thrombocyte globulin (ATG) and Cyclosporine/Methotrexate will be used according to standard current experience in the field of family and unrelated donors. The pre-transplant TKI will be continued until aplasia will develop, in order to decrease the tumor load as much as possible.The use of TKIs shortly after transplant carries the risk of inhibiting the newly transplanted hematopoietic cells, as Kit, an important kinase in normal bone marrow cells, is frequently blocked by Abl inhibitors. The use of bosutinib as post-transplant therapy is justified by the lack of Kit inhibition that distinguishes bosutinib from all other TKIs, and which could allow a minimal inhibitory activity against the transplanted normal bone marrow.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Leukemia
  • Myelogenous
  • Chronic
  • BCR-ABL Positive
Intervention  ICMJE
  • Drug: Bosutinib
    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.
    Other Names:
    • Bosulif
    • SKI-606
  • Procedure: Bone Marrow Transplant

    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

  • Drug: Bone Marrow cells
Study Arms  ICMJE Experimental: 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.
Interventions:
  • Drug: Bosutinib
  • Procedure: Bone Marrow Transplant
  • Drug: Bone Marrow cells
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 22, 2015)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2019
Estimated Primary Completion Date January 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Chronic Myeloid Leukaemia -CML- in chronic phase (CP)
  2. Failure to achieve at least a Major Cytogenetic Response (MCyR) after a minimum of 18 months of TKIs treatment
  3. Inability to tolerate 3 months of uninterrupted full dose TKIs therapy due to hematological toxicity
  4. A minimum of three treatment interruptions due to hematological toxicity Availability of a HLA-identical related donor (Matched Related Donor, MRD)
  5. 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)
  6. Target graft size (bone marrow):
  7. bone marrow: > 3 x 106 CD34+ cells/kg BW recipient or > 3 x 108 nucleated cells/kg BW
  8. Karnofsky Index > 80 %
  9. Age ≥18 and ≤70 years
  10. Adequate contraception in female patients of child-bearing potential
  11. Written informed consent

Exclusion Criteria:

  1. Secondary malignancies
  2. A hematopoietic cell transplantation-specific comorbidity index (Sorror et al Appendix C) > 4
  3. Known and manifested malignant involvement of the Central Nervous System (CNS)
  4. Active infectious disease
  5. Active human immunodeficiency virus (HIV), Hepatitis B virus (HBV) or Hepatitis B virus (HCV) infection
  6. Impaired liver function (Bilirubin > upper normal limit; Transaminases > 3.0 x upper normal limit)
  7. Impaired renal function (Creatinine-clearance < 60 ml/min; Serum Creatinine > 1.5 x upper normal limit).
  8. Pleural effusion or ascites > 1.0 L
  9. Pregnancy or lactation
  10. 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Carlo Gambacorti-Passerini, MD +390392339553 carlo.gambacorti@unimib.it
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02638467
Other Study ID Numbers  ICMJE alloCML
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Milano Bicocca
Study Sponsor  ICMJE University of Milano Bicocca
Collaborators  ICMJE IRCCS San Raffaele
Investigators  ICMJE
Principal Investigator: Carlo Gambacorti-Passerini, MD University of Milano Bicocca
PRS Account University of Milano Bicocca
Verification Date April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP