Irradiated Bone Marrow, Transplant-Related Hematologic Malignancy, Leukemia, Acute, Multiple Myeloma, Graft Vs Host Disease
Conditions
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.
Interventions
DRUGConditioning 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)
PROCEDURESCT
Stem Cell Transplant
DRUGGvHD 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)
Sponsors
IRCCS San Raffaele
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Efficacy - Relapse incidence (RI) | End of total follow-up is 365 days after transplantation of the last patient included | RI |
| Efficacy - progression free survival (PFS) | End of total follow-up is 365 days after transplantation of the last patient included | PFS |
| 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 |
| Evaluation of Transplant Safety - incidence of non-relapse mortality (NRM) | Eon day +28, day +100 and +360 | Evaluation of incidence of NRM |
| Efficacy - Overall survival (OS) | End of total follow-up is 365 days after transplantation of the last patient included | OS |
Countries
Italy
Outcome results
None listed