Rabbit anti-human thymocyte immunoglobulin for Acute myeloid leukemia | Myelodysplastic syndrome | Chronic myeloid leukemia | Myeloproliferative disorder | MDS/MPD overlap | Acute lymphoblastic leukemia | Multiple myeloma | Chronic lymphocytic leukemia | Non-Hodgkin lymphoma | Hodgkin lymphoma

Inclusion criteria

• {"criterion_text":"- Disease: Hematological malignancies confirmed histologically:\n- AML in morphological CR or not in morphological CR but not rapidly progressing (i.e. no need to give treatments such as hydroxyurea to maintain WBC count < 10 000 x10^9/mL)\n- MDS\n- CML in CP or AP\n- MPD not in blast crisis\n- MDS/MPD overlap\n- ALL in CR\n- Multiple myeloma\n- CLL\n- Non-Hodgkin’s lymphoma (aggressive NHL should have chemosensitive disease)\n- Hodgkin’s disease with chemosensitive disease or responding to checkpoint inhibitors\n- Clinical situations: Theoretical indication for a standard allo-transplant, but not feasible because:\n- Age > 50 yrs\n- Unacceptable end organ performance\n- The physician’s decision\n- The patient’s decision\n- Underlying ‘lower risk’ disease, for which RIC is preferred (eg CLL, MCL)\n- Continuation of maintenance with TKI are allowed after allo-HCT in case of Ph+ leukemia or FLT-3 mutated AML\n- Administration of other maintenance (defined as administration without evidence of relapse/progression of the underlying disease) treatments are not allowed in the protocol\n- Other inclusion criteria:\n- Male or female; fertile patients must use a reliable contraception method\n- Age 18-75 yrs (children of any age are not allowed in the protocol)\n- Informed consent given by patient or his/her guardian if indicated."}

Exclusion criteria

• {"criterion_text":"- Exclusion criteria: Any condition not fulfilling inclusion criteria\n- HIV positive\n- Non-hematological malignancy(ies) (except non-melanoma skin cancer) active < 3 years before HCT.\n- Life expectancy severely limited by disease other than malignancy\n- CNS involvement with disease refractory to intrathecal chemotherapy.\n- Terminal organ failure, except for renal failure (dialysis acceptable)\n- Cardiac: Symptomatic coronary artery disease; ejection fraction <40%; uncontrolled arrhythmia, uncontrolled hypertension;\n- Pulmonary: DLCO < 40% and/or receiving supplementary continuous oxygen, FEV1 < 40%;\n- Hepatic: Fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin >3 mg/dL, and symptomatic biliary disease;\n- Uncontrolled infection\n- Karnofsky Performance Score <70%\n- Patient is a fertile man or woman who is unwilling to use contraceptive techniques during and for 12 months following treatment\n- Patient is a female who is pregnant or breastfeeding;\n- Any condition precluding the use of melphalan or ATG"}

Primary endpoints

• {"endpoint_text":"- To assess the current GVHD-free, relapse-free survival (cGRFS) for patients conditioned with FM-PTCy or FM-ATG","definition_or_measurement_approach":"Assessment of current GVHD-free, relapse-free survival (cGRFS). The main objective specifies a 2-year cGRFS rate improvement target (from 30% to 45%) as the hypothesised measure for the pick-a-winner phase 2 comparison."}

Secondary endpoints

• {"endpoint_text":"- 1. To assess cGRFS for patients conditioned with FM-PTCy or FM-ATG separately in those transplanted with a related or an unrelated donor.","definition_or_measurement_approach":"Assessment of cGRFS stratified by donor type (related vs unrelated)."}
• {"endpoint_text":"- 2. To assess the relapse/progression rate for patients conditioned with FM-PTCy or FM-ATG.","definition_or_measurement_approach":"Measurement of relapse/progression rates post-transplant for each conditioning arm."}
• {"endpoint_text":"- 3. To assess the rates of grade II-IV and III-IV acute (at 6 months) and moderate/severe cGVHD (at 24 months) in patients conditioned with FM-PTCy or FM-ATG.","definition_or_measurement_approach":"Rates of acute GVHD grade II-IV and III-IV assessed at 6 months; rates of moderate/severe chronic GVHD assessed at 24 months."}
• {"endpoint_text":"- 4. To assess the rates of NRM as well as LFS and OS in patients conditioned with FM-PTCy or FM-ATG.","definition_or_measurement_approach":"Non-relapse mortality (NRM), leukemia-free survival (LFS) and overall survival (OS) rates measured post-transplant."}
• {"endpoint_text":"- 5. To assess the proportion of patients alive without active disease and without systemic immunosuppression 1, 2, 3, 4, 5, 7, 10 and 15-years after transplantation in patients conditioned with FM-PTCy or FM-ATG.","definition_or_measurement_approach":"Proportion alive without active disease and without systemic immunosuppression at specified timepoints (1,2,3,4,5,7,10,15 years)."}

Belgium

Earliest CTIS Part Ii Submission Date

21-10-2024

Latest Decision Or Authorization Date

23-10-2024

Processing Time Days

2

Number Of Sites

9

Number Of Participants

114

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Liege

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Belgium