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

San Donato Group (GSD)

Status and phase: Terminated; Phase 1

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

Treatments: Drug: GvHD prophylaxis; Procedure: SCT; Drug: Conditioning treatment "Treosulfan-TMI"

Study type: Interventional

Funder types: Other

Identifiers

NCT03963024

2013-002479-16

Details and patient eligibility

About

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.

Enrollment: 9 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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9 participants in 1 patient group

Single Arm Treatment

Experimental group

Description:

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

Treatment:

Procedure: SCT

Drug: Conditioning treatment "Treosulfan-TMI"

Drug: GvHD prophylaxis