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

NCT03963024 | Terminated Phase 1 DMC

• 1 other identifier: 2013-002479-16
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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

• Rate of Survival post transplant

  Evaluation of survival and engraftment

  +30 days post transplantation

Secondary Outcomes (5)

• Efficacy - progression free survival (PFS)

  End of total follow-up is 365 days after transplantation of the last patient included

• Efficacy - Overall survival (OS)

  End of total follow-up is 365 days after transplantation of the last patient included

• Efficacy - Relapse incidence (RI)

  End of total follow-up is 365 days after transplantation of the last patient included

• Evaluation of Transplant Safety - incidence of non-relapse mortality (NRM)

  Eon day +28, day +100 and +360

• Evaluation of Transplant Safety

  End of total follow-up is 365 days after transplantation of the last patient included

Study Arms (1)

Single Arm Treatment

EXPERIMENTAL

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

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

Interventions

Conditioning treatment "Treosulfan-TMI" DRUG

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)

Single Arm Treatment

SCT PROCEDURE

Stem Cell Transplant

Single Arm Treatment

GvHD prophylaxis DRUG

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)

Single Arm Treatment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• A hematopoietic cell transplantation-specific comorbidity index \> 4
• 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

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

Ospedale San Raffaele

Milan, Lombardy, 20132, Italy

Location

MeSH Terms

Conditions

Leukemia; Multiple Myeloma; Graft vs Host Disease

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 21, 2019
• First Posted: May 24, 2019
• Study Start: February 12, 2014
• Primary Completion: January 31, 2019
• Study Completion: January 31, 2019
• Last Updated: October 19, 2020

Record last verified: 2020-10

Locations

IT (1)