Clinical trial NCT03963024: Treosulfan-TMI Conditioning and Rapamycin GvHD Prophylaxis Before Allo-HSCT
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Irradiated Bone Marrow
Transplant-Related Hematologic Malignancy
Leukemia, Acute
Multiple Myeloma
Graft Vs Host Disease
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
First posted: 2019-05-24
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Evaluation of the maximum tolerated dose of TMI (FEASIBILITY of TMI)
timeFrame: From administration of TMI (-5) to transplant
measure: Rate of Survival post transplant
timeFrame: +30 days post transplantation
Secondary outcomes:
measure: Efficacy - progression free survival (PFS)
timeFrame: End of total follow-up is 365 days after transplantation of the last patient included
measure: Efficacy - Overall survival (OS)
timeFrame: End of total follow-up is 365 days after transplantation of the last patient included
measure: Efficacy - Relapse incidence (RI)
timeFrame: End of total follow-up is 365 days after transplantation of the last patient included
measure: Evaluation of Transplant Safety - incidence of non-relapse mortality (NRM)
timeFrame: Eon day +28, day +100 and +360
measure: Evaluation of Transplant Safety
timeFrame: End of total follow-up is 365 days after transplantation of the last patient included
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Ospedale San Raffaele
state: Lombardia
Study officials:
References: