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

October 13, 2020 updated by: Ciceri Fabio, IRCCS San Raffaele

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Lombardia
      • Milano, Lombardia, Italy, 20132
        • Ospedale San Raffaele

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
From administration of TMI (-5) to transplant
Rate of Survival post transplant
Time Frame: +30 days post transplantation
Evaluation of survival and engraftment
+30 days post transplantation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy - progression free survival (PFS)
Time Frame: End of total follow-up is 365 days after transplantation of the last patient included
PFS
End of total follow-up is 365 days after transplantation of the last patient included
Efficacy - Overall survival (OS)
Time Frame: End of total follow-up is 365 days after transplantation of the last patient included
OS
End of total follow-up is 365 days after transplantation of the last patient included
Efficacy - Relapse incidence (RI)
Time Frame: End of total follow-up is 365 days after transplantation of the last patient included
RI
End of total follow-up is 365 days after transplantation of the last patient included
Evaluation of Transplant Safety - incidence of non-relapse mortality (NRM)
Time Frame: Eon day +28, day +100 and +360
Evaluation of incidence of NRM
Eon day +28, day +100 and +360
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
End of total follow-up is 365 days after transplantation of the last patient included

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS San Raffaele

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 12, 2014

Primary Completion (Actual)

January 31, 2019

Study Completion (Actual)

January 31, 2019

Study Registration Dates

First Submitted

May 21, 2019

First Submitted That Met QC Criteria

May 23, 2019

First Posted (Actual)

May 24, 2019

Study Record Updates

Last Update Posted (Actual)

October 19, 2020

Last Update Submitted That Met QC Criteria

October 13, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2013-002479-16

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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