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

Multiple Myeloma Clinical Trial

— TrRaMM-TMI  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03963024
• Other study ID #: 2013-002479-16
• Status: Terminated
• Phase: Phase 1
• Start date: February 12, 2014
• Est. completion date: January 31, 2019

Study information

• Verified date: October 2020
• Source: IRCCS San Raffaele
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: January 31, 2019
• Est. primary completion date: January 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Graft Vs Host Disease
• Hematologic Neoplasms
• Irradiated Bone Marrow
• Leukemia, Acute
• Multiple Myeloma
• Neoplasms
• Transplant-Related Hematologic Malignancy

Intervention

Drug:
• Conditioning 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)

Procedure:
• SCT
Stem Cell Transplant

Drug:
• GvHD 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)

Locations

Country	Name	City	State
Italy	Ospedale San Raffaele	Milano	Lombardia

Sponsors (1)

Lead Sponsor	Collaborator
IRCCS San Raffaele

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of the maximum tolerated dose of TMI (FEASIBILITY of TMI)	To determine the maximum tolerated dose of TMI when combined with conditioning chemotherapy to transplant according to TrRaMM schedule	From administration of TMI (-5) to transplant
Primary	Rate of Survival post transplant	Evaluation of survival and engraftment	+30 days post transplantation
Secondary	Efficacy - progression free survival (PFS)	PFS	End of total follow-up is 365 days after transplantation of the last patient included
Secondary	Efficacy - Overall survival (OS)	OS	End of total follow-up is 365 days after transplantation of the last patient included
Secondary	Efficacy - Relapse incidence (RI)	RI	End of total follow-up is 365 days after transplantation of the last patient included
Secondary	Evaluation of Transplant Safety - incidence of non-relapse mortality (NRM)	Evaluation of incidence of NRM	Eon day +28, day +100 and +360
Secondary	Evaluation of Transplant Safety	Cumulative of incidence and cumulative severity of GvHD	End of total follow-up is 365 days after transplantation of the last patient included