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

Phase 1

Terminated

• Conditions: Irradiated Bone Marrow; Transplant-Related Hematologic Malignancy; Leukemia, Acute; Multiple Myeloma; Graft Vs Host Disease
• Interventions: Drug: Conditioning treatment "Treosulfan-TMI"; Procedure: SCT; Drug: GvHD prophylaxis

• Registration Number: NCT03963024
• Lead Sponsor: IRCCS San Raffaele

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 available

Study Timeline

• Study Start: 2014-02-12
• Primary Completion: 2019-01-31
• Study Completion: 2019-01-31
• Study First Submitted: 2019-05-21
• Study First Submitted QC: 2019-05-23
• Study First Posted: 2019-05-24
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-13
• Last Update Posted: 2020-10-19

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 9

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single Arm Treatment	SCT	Conditioning treatment "Treosulfan+TMI"; SCT; GvHD prophylaxis;
Single Arm Treatment	Conditioning treatment "Treosulfan-TMI"	Conditioning treatment "Treosulfan+TMI"; SCT; GvHD prophylaxis;
Single Arm Treatment	GvHD prophylaxis	Conditioning treatment "Treosulfan+TMI"; SCT; GvHD prophylaxis;

Primary Outcome Measures

Name	Time	Method
Evaluation of the maximum tolerated dose of TMI (FEASIBILITY of TMI)	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	+30 days post transplantation	Evaluation of survival and engraftment

Secondary Outcome Measures

Name	Time	Method
Efficacy - progression free survival (PFS)	End of total follow-up is 365 days after transplantation of the last patient included	PFS
Efficacy - Overall survival (OS)	End of total follow-up is 365 days after transplantation of the last patient included	OS
Efficacy - Relapse incidence (RI)	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)	Eon day +28, day +100 and +360	Evaluation of incidence of NRM
Evaluation of Transplant Safety	End of total follow-up is 365 days after transplantation of the last patient included	Cumulative of incidence and cumulative severity of GvHD

Trial Locations

Locations (1)

Ospedale San Raffaele; 🇮🇹 Milano, Lombardia, Italy