4006-776-356 出国就医服务电话

免费获得国外相关药品，最快 1 个工作日回馈药物信息

出境医 / 临床实验 / Treosulfan-TMI Conditioning and Rapamycin GvHD Prophylaxis Before Allo-HSCT (TrRaMM-TMI)

Treosulfan-TMI Conditioning and Rapamycin GvHD Prophylaxis Before Allo-HSCT (TrRaMM-TMI)

Study Description
Brief Summary:

TrRaMM-TMI is a phase I trial to evaluate the feasibility and efficacy of an original sequential TMI/TrRaMM (Total Marrow Irradiation/Treosulfan-Rapamycin-Mycophenolate Mofetil) schedule in patients with hematological malignancies in advanced stage of disease undergoing an allogenic Stem Cell Transplant (SCT).

The aim is to determine the maximum tolerated dose of TMI when combined with conditioning chemotherapy to transplant according to TrRaMM schedule.


Condition or disease Intervention/treatment Phase
Irradiated Bone Marrow Transplant-Related Hematologic Malignancy Leukemia, Acute Multiple Myeloma Graft Vs Host Disease Drug: Conditioning treatment "Treosulfan-TMI" Procedure: SCT Drug: GvHD prophylaxis Phase 1

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treosulfan and Total-marrow Irradiation (TMI) Based Conditioning With Rapamycin Based Graft vs. Host Disease (GvHD) Prophylaxis for Allogenic Stem Cell Transplantation (Allo-HSCT) in Patients With High-risk Hematological Malignancies
Actual Study Start Date : February 12, 2014
Actual Primary Completion Date : January 31, 2019
Actual Study Completion Date : January 31, 2019
Arms and Interventions
Arm Intervention/treatment
Experimental: Single Arm Treatment
Conditioning treatment "Treosulfan+TMI"; SCT; GvHD prophylaxis;
 Drug: Conditioning treatment "Treosulfan-TMI"
Treosulfan i.v.: 14 g/m²/d (day -6 to -4) Fludarabine i.v.: 30 mg/m²/d (day -6 to -2) Antithymocyte globulin (ATG)-Fresenius i.v.: 5/0 mg/kg (day -4 to -2) Mabthera i.v.: 200/0* mg/m2 (day -1) TMI: (10 Gy) 2 Gy bis in die (BID) (day -2 to -1) or TMI: (12 Gy) 2 Gy BID (day -3 to -1) or TMI: (14 Gy) 2 Gy BID (day -3 to -1)

Procedure: SCT
Stem Cell Transplant

Drug: GvHD prophylaxis
Rapamycin p.o.: 4 mg/d, (target 8-15 ng/ml) (starting day -7) Mycofenolate mofetile: 10 mg/kg tid, (Maximum dose 720 mg/tid) (starting from day 0)
Outcome Measures
Primary Outcome Measures :
  1. Evaluation of the maximum tolerated dose of TMI (FEASIBILITY of TMI) [ Time Frame: From administration of TMI (-5) to transplant ]
    To determine the maximum tolerated dose of TMI when combined with conditioning chemotherapy to transplant according to TrRaMM schedule

  2. Rate of Survival post transplant [ Time Frame: +30 days post transplantation ]
    Evaluation of survival and engraftment


Secondary Outcome Measures :
  1. Efficacy - progression free survival (PFS) [ Time Frame: End of total follow-up is 365 days after transplantation of the last patient included ]
    PFS

  2. Efficacy - Overall survival (OS) [ Time Frame: End of total follow-up is 365 days after transplantation of the last patient included ]
    OS

  3. Efficacy - Relapse incidence (RI) [ Time Frame: End of total follow-up is 365 days after transplantation of the last patient included ]
    RI

  4. Evaluation of Transplant Safety - incidence of non-relapse mortality (NRM) [ Time Frame: Eon day +28, day +100 and +360 ]
    Evaluation of incidence of NRM

  5. Evaluation of Transplant Safety [ Time Frame: End of total follow-up is 365 days after transplantation of the last patient included ]
    Cumulative of incidence and cumulative severity of GvHD


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with haematological malignancies such as

    • any acute myeloid leukemia (AML) beyond Complete Remission (CR) 1
    • any acute lymphoblastic leukemia (ALL) beyond CR1
    • multiple myeloma (MM) at any relapse/progression, except refractory disease
    • MM with unfavourable cytogenetic profile at diagnosis
    • MM with less than a partial response (PR) after induction therapy
  • Karnofsky Index ≥ 80 %
  • Adequate contraception in female patients of child-bearing potential.
  • Written informed consent

  • Availability of one of the following:

    • A matched related or unrelated donor (MRD or MUD)

Exclusion Criteria:

  • A hematopoietic cell transplantation-specific comorbidity index > 4
  • Active non-controlled infectious disease at the moment of inclusion
  • Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
  • Impaired liver function (Bilirubin > 2.0 x 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 treosulfan and/or fludarabine and/or rapamycin
  • Non-co-operative behaviour or non-compliance
  • Psychiatric diseases or conditions that might impair the ability to give informed consent
  • Previous spinal cord radiotherapy with dose ≥ 45 Gy equivalent
Contacts and Locations

Locations
Layout table for location information
Italy
Ospedale San Raffaele
Milano, Lombardia, Italy, 20132
Sponsors and Collaborators
IRCCS San Raffaele
Tracking Information
First Submitted Date  ICMJE May 21, 2019
First Posted Date  ICMJE May 24, 2019
Last Update Posted Date October 19, 2020
Actual Study Start Date  ICMJE February 12, 2014
Actual Primary Completion Date January 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 23, 2019)
  • Evaluation of the maximum tolerated dose of TMI (FEASIBILITY of TMI) [ Time Frame: From administration of TMI (-5) to transplant ]
    To determine the maximum tolerated dose of TMI when combined with conditioning chemotherapy to transplant according to TrRaMM schedule
  • Rate of Survival post transplant [ Time Frame: +30 days post transplantation ]
    Evaluation of survival and engraftment
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 24, 2019)
  • Efficacy - progression free survival (PFS) [ Time Frame: End of total follow-up is 365 days after transplantation of the last patient included ]
    PFS
  • Efficacy - Overall survival (OS) [ Time Frame: End of total follow-up is 365 days after transplantation of the last patient included ]
    OS
  • Efficacy - Relapse incidence (RI) [ Time Frame: End of total follow-up is 365 days after transplantation of the last patient included ]
    RI
  • Evaluation of Transplant Safety - incidence of non-relapse mortality (NRM) [ Time Frame: Eon day +28, day +100 and +360 ]
    Evaluation of incidence of NRM
  • Evaluation of Transplant Safety [ Time Frame: End of total follow-up is 365 days after transplantation of the last patient included ]
    Cumulative of incidence and cumulative severity of GvHD
Original Secondary Outcome Measures  ICMJE
 (submitted: May 23, 2019)
  • Efficay - progression free survival [ Time Frame: End of total follow-up is 365 days after transplantation of the last patient included ]
    PFS (progression free survival)
  • Efficay - Overall survival [ Time Frame: End of total follow-up is 365 days after transplantation of the last patient included ]
    OS (Overall survival)
  • Efficay - Relapse incidence [ Time Frame: End of total follow-up is 365 days after transplantation of the last patient included ]
    RI (Relapse incidence)
  • Evaluation of Transplant Safety - incidence of non-relapse mortality [ Time Frame: Eon day +28, day +100 and +360 ]
    Evaluation of incidence of non-relapse mortality NRM (Non-relapse mortality)
  • Evaluation of Transplant Safety [ Time Frame: End of total follow-up is 365 days after transplantation of the last patient included ]
    Cumulative of incidence and cumulative severity of GvHD
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Treosulfan-TMI Conditioning and Rapamycin GvHD Prophylaxis Before Allo-HSCT
Official Title  ICMJE Treosulfan and Total-marrow Irradiation (TMI) Based Conditioning With Rapamycin Based Graft vs. Host Disease (GvHD) Prophylaxis for Allogenic Stem Cell Transplantation (Allo-HSCT) in Patients With High-risk Hematological Malignancies
Brief Summary

TrRaMM-TMI is a phase I trial to evaluate the feasibility and efficacy of an original sequential TMI/TrRaMM (Total Marrow Irradiation/Treosulfan-Rapamycin-Mycophenolate Mofetil) schedule in patients with hematological malignancies in advanced stage of disease undergoing an allogenic Stem Cell Transplant (SCT).

The aim is to determine the maximum tolerated dose of TMI when combined with conditioning chemotherapy to transplant according to TrRaMM schedule.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Irradiated Bone Marrow
  • Transplant-Related Hematologic Malignancy
  • Leukemia, Acute
  • Multiple Myeloma
  • Graft Vs Host Disease
Intervention  ICMJE
  • Drug: Conditioning treatment "Treosulfan-TMI"
    Treosulfan i.v.: 14 g/m²/d (day -6 to -4) Fludarabine i.v.: 30 mg/m²/d (day -6 to -2) Antithymocyte globulin (ATG)-Fresenius i.v.: 5/0 mg/kg (day -4 to -2) Mabthera i.v.: 200/0* mg/m2 (day -1) TMI: (10 Gy) 2 Gy bis in die (BID) (day -2 to -1) or TMI: (12 Gy) 2 Gy BID (day -3 to -1) or TMI: (14 Gy) 2 Gy BID (day -3 to -1)
  • Procedure: SCT
    Stem Cell Transplant
  • Drug: GvHD prophylaxis
    Rapamycin p.o.: 4 mg/d, (target 8-15 ng/ml) (starting day -7) Mycofenolate mofetile: 10 mg/kg tid, (Maximum dose 720 mg/tid) (starting from day 0)
Study Arms  ICMJE Experimental: Single Arm Treatment
Conditioning treatment "Treosulfan+TMI"; SCT; GvHD prophylaxis;
Interventions:
  • Drug: Conditioning treatment "Treosulfan-TMI"
  • Procedure: SCT
  • Drug: GvHD prophylaxis
Publications * Not Provided

*   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 Terminated
Actual Enrollment  ICMJE
 (submitted: October 13, 2020) 		9
Original Estimated Enrollment  ICMJE
 (submitted: May 23, 2019) 		18
Actual Study Completion Date  ICMJE January 31, 2019
Actual Primary Completion Date January 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with haematological malignancies such as

    • any acute myeloid leukemia (AML) beyond Complete Remission (CR) 1
    • any acute lymphoblastic leukemia (ALL) beyond CR1
    • multiple myeloma (MM) at any relapse/progression, except refractory disease
    • MM with unfavourable cytogenetic profile at diagnosis
    • MM with less than a partial response (PR) after induction therapy
  • Karnofsky Index ≥ 80 %
  • Adequate contraception in female patients of child-bearing potential.
  • Written informed consent

  • Availability of one of the following:

    • A matched related or unrelated donor (MRD or MUD)

Exclusion Criteria:

  • A hematopoietic cell transplantation-specific comorbidity index > 4
  • Active non-controlled infectious disease at the moment of inclusion
  • Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
  • Impaired liver function (Bilirubin > 2.0 x 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 treosulfan and/or fludarabine and/or rapamycin
  • Non-co-operative behaviour or non-compliance
  • Psychiatric diseases or conditions that might impair the ability to give informed consent
  • Previous spinal cord radiotherapy with dose ≥ 45 Gy equivalent
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 information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03963024
Other Study ID Numbers  ICMJE 2013-002479-16
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ciceri Fabio, IRCCS San Raffaele
Study Sponsor  ICMJE IRCCS San Raffaele
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account IRCCS San Raffaele
Verification Date October 2020

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

治疗医院

新药特效药

治疗案例

前沿医讯