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

• Sponsor: IRCCS San Raffaele (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03963024
• Collaborator: (none)
• Enrollment: 9
• Location: 1
• Arm: 1
• Actual Duration (Months): 59.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Irradiated Bone Marrow; Transplant-Related Hematologic Malignancy; Leukemia, Acute; Multiple Myeloma; Graft Vs Host Disease	Drug: Conditioning treatment "Treosulfan-TMI"; Procedure: SCT; Drug: GvHD prophylaxis	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Feb 12, 2014
• Actual Primary Completion Date: Jan 31, 2019
• Actual Study Completion Date: Jan 31, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Single Arm Treatment Conditioning treatment "Treosulfan+TMI"; SCT; GvHD prophylaxis;

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)

Outcome Measures

Primary Outcome Measures

1. 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

2. Rate of Survival post transplant [+30 days post transplantation]

   Evaluation of survival and engraftment

Secondary Outcome Measures

1. Efficacy - progression free survival (PFS) [End of total follow-up is 365 days after transplantation of the last patient included]

   PFS

2. Efficacy - Overall survival (OS) [End of total follow-up is 365 days after transplantation of the last patient included]

   OS

3. Efficacy - Relapse incidence (RI) [End of total follow-up is 365 days after transplantation of the last patient included]

   RI

4. Evaluation of Transplant Safety - incidence of non-relapse mortality (NRM) [Eon day +28, day +100 and +360]

   Evaluation of incidence of NRM

5. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ospedale San Raffaele	Milano	Lombardia	Italy	20132

Sponsors and Collaborators

• IRCCS San Raffaele

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ciceri Fabio, Professor, IRCCS San Raffaele
• ClinicalTrials.gov Identifier: NCT03963024
• Other Study ID Numbers: 2013-002479-16
• First Posted: May 24, 2019
• Last Update Posted: Oct 19, 2020
• Last Verified: Oct 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms; Hematologic Neoplasms; Graft vs Host Disease; Treosulfan

Study Results

No Results Posted as of Oct 19, 2020