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

• Status: Terminated
• Trial end date: 2019-01-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: IRCCS San Raffaele
• Treatments: Busulfan; Everolimus; Sirolimus; Treosulfan

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