Treosulfan-TMI Conditioning and Rapamycin GvHD Prophylaxis Before Allo-HSCT

NCT ID: NCT03963024

Last Updated: 2020-10-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

9 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-02-12

Study Completion Date

2019-01-31

Brief Summary

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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

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Conditions

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Irradiated Bone Marrow Transplant-Related Hematologic Malignancy Leukemia, Acute Multiple Myeloma Graft Vs Host Disease

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Single Arm Treatment

Conditioning treatment "Treosulfan+TMI"; SCT; GvHD prophylaxis;

Group Type EXPERIMENTAL

Conditioning treatment "Treosulfan-TMI"

Intervention Type DRUG

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)

SCT

Intervention Type PROCEDURE

Stem Cell Transplant

GvHD prophylaxis

Intervention Type DRUG

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)

Interventions

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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)

Intervention Type DRUG

SCT

Stem Cell Transplant

Intervention Type PROCEDURE

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)

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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IRCCS San Raffaele

OTHER

Sponsor Role lead

Responsible Party

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Ciceri Fabio

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Ospedale San Raffaele

Milan, Lombardy, Italy

Site Status

Countries

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Italy

Other Identifiers

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2013-002479-16

Identifier Type: -

Identifier Source: org_study_id

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