Acute Leukemia (Category)
Conditions
Keywords
high risk acute leukemia, HSV-TK, Haploidentical HCT, GvHD, GvL, Immunoreconstitution
Brief summary
The main objective of this randomized trial is to compare disease-free survival (DFS) in high risk leukemia patients who underwent haploidentical HCT followed by an add back strategy of HSV-Tk donor lymphocytes or standard haploidentical HCT
Detailed description
Delayed immune-reconstitution remains one of the main limitation of haploidentical stem cell transplantation. The risk of severe infections remains high for several months and CD3+ reconstitution could take more than 10 months. The low number of lymphocytes infused with the graft, the degree of HLA (Human Leukocyte Antigen) disparity, and a reduced thymic function in adults and differences in host/donor antigen presenting cells are contributing causes. The infusions of HSV-TK engineered lymphocytes may represent a significant therapeutic improvement in haploidentical HCT (hematopoietic cell transplantation), because it remarkably may enhance both GvL (Graft versus Leukemia) activity, thus reducing the occurrence of disease relapse, and post-transplant immune reconstitution in the absence of chronic immune suppression, thus decreasing the rate of both post-transplant opportunistic infections and transplant-related mortality. Furthermore, the efficient control of GvHD achieved via the suicide mechanism allows also the multiple infusion of HSV-TK-treated donor lymphocytes, when needed, that might further improve post-transplant host immune reconstitution, and survival in patients receiving haplo-HCT. Finally, this therapeutic approach can become a valuable option for all candidates, including patients with advanced disease and older age. The proposed clinical trial represents an innovative therapeutic treatment for patients affected by high risk acute leukemia, who have undergone haploidentical stem cell transplantation.
Interventions
GENETICHSV-Tk
Infusion of approximately 1±0.2 x 10\^7 HSV-Tk genetically modified CD3+ cells/Kg between day +21 and day +49 after haploidentical HCT; in absence of immune reconstitution and GvHD further infusions up to 4 will be administered on monthly basis.
OTHERT-cell depleted or T-cell replete strategies
Haploidentical HCT with the infusion of CD34+ cells plus a fixed dose of T cells (1 x 10\^4/Kg) or unmanipulated haploidentical stem cell transplantation followed by high-dose cyclophosphamide as part of GvHD prophylaxis
Sponsors
AGC Biologics S.p.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Any of the following conditions: 1. AML and ALL in 1st complete remission (CR1) 2. AML and ALL in 2nd or subsequent CR 3. secondary AML in CR 4. AML and ALL in 1st or 2nd relapse or primary refractory * Family donor with patient-donor number of HLA mismatches ≥ 2 (full haploidentical), or family donors sharing one HLA-haplotype with the patient * Stable clinical conditions and life expectancy \> 3 months * PS ECOG \< 2 * Serum creatinine \< 1.5 x ULN * Bilirubin \< 1.5 x ULN; transaminases \< 3 x ULN * Left ventricular ejection fraction \> 45% * QTc interval \< 450 ms * DLCO \> 50% * Patients, or legal guardians, and donors must sign an informed consent indicating that they are aware this is a research study and have been told of its possible benefits and toxic side effects
Exclusion criteria
* Patients with life-threatening condition or complication other than their basic condition * Contraindication to haploidentical HCT as defined by the Investigator * Patients with active CNS disease * Pregnant or lactation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival (DFS) | From the date of randomization, assessed up to 12 months | Defined as the measure from the date of randomization until the date of relapse (or progression), or death from any cause, whichever occurs first. Disease relapse or progression was determined by the Investigator based on the following disease examination: * Morphology (bone marrow or peripheral blood) * Confirmation of mixed or full chimerism (evaluation of the degree of chimerism between donor/host, according to institutional clinical practice, on bone marrow or peripheral blood) * Cytogenetic and/or molecular and/or other tests, according to institutional clinical practice (bone marrow or peripheral blood). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immune Reconstitution (IR) | Weekly up to IR after engraftment of HCT, monthly for 6 months from date of IR and then at month 9 and 12 | Assess how many patients experience IR. For the assessment, competing risk analysis was performed considering death, relapse, and disease progression as competing events. Patients who were still alive and had no recovery (IR) nor relapse (or progression) were censored.IR is defined as achieving a level of circulating CD3+ ≥ 100/μL for two consecutive observations. The following laboratory examinations are performed: * Hematology: WBC (full and differential), RBC, platelets, Hb, Htc, MCV, MPV, serology CMV (PCR and antigenemia). * Blood chemistry: AST, ALT, γGT, total bilirubin, LDH. |
| Engraftment Rate | At day 15 after HCT, monthly for 6 months after HCT and then at month 9 and 12 | Defined as the persistent blood cells count above predefined level. |
| Cumulative Incidence of Grade 2, 3, or 4 Acute GvHD (aGvHD) | from the date of HCT until the date of the first occurrence of aGvHD, assessed up to 6 months | Diagnosed and graded according to standard criteria. Grade 1: Skin: Stage 1-2: Rash on \< 25% of skin or Rash on 25-50% of skin Liver: Stage 1-2: Bilirubin 2-3 mg/dl or Bilirubin 3-6 mg/dl Gastrointestinal: Stage 1-2: Diarrhoea \> 500 ml/day or persistent nausea or Diarrhoea \> 1000ml/day |
| Cumulative Incidence of Chronic GvHD (cGvHD) | From the date of HCT until the date of the first occurrence of cGvHD, assessed up to 12 months | Diagnosed and graded according to standard NIH consensus criteria |
| Duration of GvHD Episodes | From the date of start until the date of resolution and duration of immunosuppressive treatments administered for controlling GvHD assessed up to 12 months | Diagnosed and graded according to standard NIH consensus criteria |
| Overall Survival (OS) | From the date of randomization to the date of death, assessed up to 12 months | any death without previous occurrence of a documented relapse (or progression).Patients alive or without any follow up will be censored. |
| Incidence and Duration of Infectious Episodes and Infectious Disease Mortality | From randomization to the date of resolution, assessed up to 12 months | Diagnosis, monitoring and treatment of infectious relevant events |
| Evaluate the Acute and Long-term Toxicity Related to the HSV-Tk Infusions | From HSV-Tk infusions to the date of resolution, assessed up to 12 months | Toxicity profile of HSV-Tk infusions |
| Quality of Life (QoL) and Medical Care Utilization (MCU) in Both Arms | from randomization up to 12 months | Medical resource use data collected will be used in health economic analyses where it may be combined with other data from other sources such as cost data or other clinical parameters. |
| Non-relapse Mortality (NRM) | From the date of randomization to the date of death, assessed up to 12 months. | Defined for all patients as any death without previous occurrence of a documented relapse (or progression). Absence of relapse was determined by the Investigator based on the following disease examination: * Morphology (bone marrow or peripheral blood) * Confirmation of mixed or full chimerism (evaluation of the degree of chimerism between donor/host, according to institutional clinical practice, on bone marrow or peripheral blood) * Cytogenetic and/or molecular and/or other tests, according to institutional clinical practice (bone marrow or peripheral blood). Gray's test was used to compare the sub-distribution functions of the death without previous relapse (or progression) and relapse (or progression) events in the two treatment groups. |
| Cumulative Incidence of Relapse (CIR) | from the date of randomization to the date of the first occurrence of relapse, assessed up to 12 months | Defined on the basis of morphologic evidence of leukaemia in bone marrow or other sites. Gray's test was used to compare the sub-distribution functions of relapse (or progression) events in the two treatment groups. Patients alive without relapse (or regression) will be censored |
Countries
Belgium, France, Germany, Greece, Israel, Italy, Lithuania, Portugal, Spain, United States
Participant flow
Recruitment details
Study period: Date of First patient enrolled: 12.04.2010; Date of Last patient completed: 30.11.2019; Date of End of study: 30.11.2019.
Pre-assignment details
Planned sample size n.170; Randomized patients n. 92. Discontinued n. 70; Early termination by the Sponsor n. 22;
Participants by arm
| Arm | Count |
|---|---|
| A - Experimental Arm patients received the infusion of CD34+ cells plus a dose of T cells (approximately 1 x 104/Kg), followed by the infusion of HSV-TK genetically modified CD3+ cells In absence of immune reconstitution and GvHD further infusions up to 4 will be administered on monthly basis. | 64 |
| B- Comparator Arm the physician chose whether the patient received the infusion of CD34+ cells plus a dose of T cells (approximately 1 x 104/Kg) or an unmanipulated haploidentical bone marrow or peripheral blood transplant followed by high-dose cyclophosphamide. | 28 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 35 | 17 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Medical decision | 4 | 0 |
| Overall Study | non-randomized | 1 | 0 |
| Overall Study | Patients who did not receive a single dose | 7 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Relapse | 1 | 2 |
| Overall Study | Study terminated by Sponsor | 14 | 8 |
Baseline characteristics
| Characteristic | A - Experimental Arm | B- Comparator Arm | Total |
|---|---|---|---|
| Age, Continuous | 45.89 years STANDARD_DEVIATION 15.29 | 51.43 years STANDARD_DEVIATION 12.41 | 47.58 years STANDARD_DEVIATION 14.63 |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 3 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Caucasian | 55 Participants | 24 Participants | 79 Participants |
| Race/Ethnicity, Customized Other | 5 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Female | 23 Participants | 9 Participants | 32 Participants |
| Sex: Female, Male Male | 41 Participants | 19 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 35 / 53 | 17 / 27 |
| other Total, other adverse events | 22 / 53 | 0 / 27 |
| serious Total, serious adverse events | 35 / 53 | 17 / 27 |
Outcome results
Primary
Disease-free Survival (DFS)
Defined as the measure from the date of randomization until the date of relapse (or progression), or death from any cause, whichever occurs first. Disease relapse or progression was determined by the Investigator based on the following disease examination: * Morphology (bone marrow or peripheral blood) * Confirmation of mixed or full chimerism (evaluation of the degree of chimerism between donor/host, according to institutional clinical practice, on bone marrow or peripheral blood) * Cytogenetic and/or molecular and/or other tests, according to institutional clinical practice (bone marrow or peripheral blood).
Time frame: From the date of randomization, assessed up to 12 months
Population: The analysis has been performed for all patients in the two treatment arms. The NRM analysis was performed on the Intention to Treat Population (ITT) and Per Protocol (PP) set populations.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| A-Experimental Arm | Disease-free Survival (DFS) | DFS on ITT | Patients with DFS event | 45 Participants |
| A-Experimental Arm | Disease-free Survival (DFS) | DFS on ITT | Censored patients | 19 Participants |
| A-Experimental Arm | Disease-free Survival (DFS) | DFS on PP Set | Patients with DFS event | 25 Participants |
| A-Experimental Arm | Disease-free Survival (DFS) | DFS on PP Set | Censored patients | 13 Participants |
| A-Experimental Arm | Disease-free Survival (DFS) | DFS on ITT - day 21 after transplant | Patients with DFS event | 38 Participants |
| A-Experimental Arm | Disease-free Survival (DFS) | DFS on ITT - day 21 after transplant | Censored patients | 17 Participants |
| A-Experimental Arm | Disease-free Survival (DFS) | DFS on PP Set day 21 after transplant | Patients with DFS event | 25 Participants |
| A-Experimental Arm | Disease-free Survival (DFS) | DFS on PP Set day 21 after transplant | Censored patients | 13 Participants |
| B - Control Arm | Disease-free Survival (DFS) | DFS on PP Set day 21 after transplant | Censored patients | 8 Participants |
| B - Control Arm | Disease-free Survival (DFS) | DFS on ITT | Patients with DFS event | 20 Participants |
| B - Control Arm | Disease-free Survival (DFS) | DFS on ITT - day 21 after transplant | Patients with DFS event | 20 Participants |
| B - Control Arm | Disease-free Survival (DFS) | DFS on ITT | Censored patients | 8 Participants |
| B - Control Arm | Disease-free Survival (DFS) | DFS on PP Set day 21 after transplant | Patients with DFS event | 18 Participants |
| B - Control Arm | Disease-free Survival (DFS) | DFS on PP Set | Patients with DFS event | 18 Participants |
| B - Control Arm | Disease-free Survival (DFS) | DFS on ITT - day 21 after transplant | Censored patients | 8 Participants |
| B - Control Arm | Disease-free Survival (DFS) | DFS on PP Set | Censored patients | 8 Participants |
p-value: 0.8974Log Rank
Comparison: DFS- Intention-To-Treat population- from baseline to day 21p-value: 0.7612Wilcoxon (Mann-Whitney)
p-value: 0.5995Log Rank
Comparison: DFS- Intention-To-Treat population - day 21 after transplantp-value: 0.4078Wilcoxon (Mann-Whitney)
Comparison: DFS- Per-Protocol Setp-value: 0.3351Log Rank
Comparison: DFS- Per-Protocol Setp-value: 0.1233Wilcoxon (Mann-Whitney)
Comparison: DFS- Per-Protocol Set DFS-day 21 after transplantp-value: 0.5995Log Rank
Comparison: DFS- Per-Protocol Set DFS-day 21 after transplantp-value: 0.4078Wilcoxon (Mann-Whitney)
Secondary
Cumulative Incidence of Chronic GvHD (cGvHD)
Diagnosed and graded according to standard NIH consensus criteria
Time frame: From the date of HCT until the date of the first occurrence of cGvHD, assessed up to 12 months
Population: Due to the early termination of the study, the analysis was not performed because data were not collected for this Outcome Measure
Secondary
Cumulative Incidence of Grade 2, 3, or 4 Acute GvHD (aGvHD)
Diagnosed and graded according to standard criteria. Grade 1: Skin: Stage 1-2: Rash on \< 25% of skin or Rash on 25-50% of skin Liver: Stage 1-2: Bilirubin 2-3 mg/dl or Bilirubin 3-6 mg/dl Gastrointestinal: Stage 1-2: Diarrhoea \> 500 ml/day or persistent nausea or Diarrhoea \> 1000ml/day
Time frame: from the date of HCT until the date of the first occurrence of aGvHD, assessed up to 6 months
Population: Due to the early termination of the study, the analysis was not performed because data were not collected for this Outcome Measure
Secondary
Cumulative Incidence of Relapse (CIR)
Defined on the basis of morphologic evidence of leukaemia in bone marrow or other sites. Gray's test was used to compare the sub-distribution functions of relapse (or progression) events in the two treatment groups. Patients alive without relapse (or regression) will be censored
Time frame: from the date of randomization to the date of the first occurrence of relapse, assessed up to 12 months
Population: The analysis has been performed for all patients in the two treatment arms. The NRM analysis was performed on the Intention to Treat Population (ITT) and Per Protocol (PP) set populations.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| A-Experimental Arm | Cumulative Incidence of Relapse (CIR) | CIR on PP Set | Patients with relapse or progression | 11 Participants |
| A-Experimental Arm | Cumulative Incidence of Relapse (CIR) | CIR on ITT population - CIR | Censored patients | 19 Participants |
| A-Experimental Arm | Cumulative Incidence of Relapse (CIR) | CIR on PP Set | Deaths without previous relapse or progression | 14 Participants |
| A-Experimental Arm | Cumulative Incidence of Relapse (CIR) | CIR on ITT population - CIR | Deaths without previous relapse or progression | 27 Participants |
| A-Experimental Arm | Cumulative Incidence of Relapse (CIR) | CIR on PP Set | Censored patients | 13 Participants |
| A-Experimental Arm | Cumulative Incidence of Relapse (CIR) | CIR on ITT population - CIR | Patients with relapse or progression | 18 Participants |
| B - Control Arm | Cumulative Incidence of Relapse (CIR) | CIR on PP Set | Censored patients | 8 Participants |
| B - Control Arm | Cumulative Incidence of Relapse (CIR) | CIR on ITT population - CIR | Patients with relapse or progression | 11 Participants |
| B - Control Arm | Cumulative Incidence of Relapse (CIR) | CIR on ITT population - CIR | Censored patients | 8 Participants |
| B - Control Arm | Cumulative Incidence of Relapse (CIR) | CIR on PP Set | Patients with relapse or progression | 11 Participants |
| B - Control Arm | Cumulative Incidence of Relapse (CIR) | CIR on PP Set | Deaths without previous relapse or progression | 7 Participants |
| B - Control Arm | Cumulative Incidence of Relapse (CIR) | CIR on ITT population - CIR | Deaths without previous relapse or progression | 9 Participants |
Comparison: This Statistical Analysis refers to ITT Patients with relapse or progression and was performed with Gray's Test for Equality of Cumulative Incidence Functionsp-value: 0.3526Chi-squared
Comparison: this Gray's Statistical Analysis refers to ITT Deaths patients without previous relapse or progression and was performed with Test for Equality of Cumulative Incidence Functionsp-value: 0.4035Chi-squared
Comparison: this Gray's Statistical Analysis refers to PPS patients with relapse or progression and was performed with Test for Equality of Cumulative Incidence Functionsp-value: 0.2607Chi-squared
Comparison: this Gray's Statistical Analysis refers to PPS Deaths patients without previous relapse or progression and was performed with Test for Equality of Cumulative Incidence Functionp-value: 0.5929Chi-squared
Secondary
Duration of GvHD Episodes
Diagnosed and graded according to standard NIH consensus criteria
Time frame: From the date of start until the date of resolution and duration of immunosuppressive treatments administered for controlling GvHD assessed up to 12 months
Population: Due to the early termination of the study, the analysis was not performed.because data were not collected for this Outcome Measure
Secondary
Engraftment Rate
Defined as the persistent blood cells count above predefined level.
Time frame: At day 15 after HCT, monthly for 6 months after HCT and then at month 9 and 12
Population: Due to the early termination of the study, the analysis was not performed because data were not collected for this Outcome Measure
Secondary
Evaluate the Acute and Long-term Toxicity Related to the HSV-Tk Infusions
Toxicity profile of HSV-Tk infusions
Time frame: From HSV-Tk infusions to the date of resolution, assessed up to 12 months
Population: Due to the early termination of the study, the analysis was not performed because data were not collected for this Outcome Measure
Secondary
Immune Reconstitution (IR)
Assess how many patients experience IR. For the assessment, competing risk analysis was performed considering death, relapse, and disease progression as competing events. Patients who were still alive and had no recovery (IR) nor relapse (or progression) were censored.IR is defined as achieving a level of circulating CD3+ ≥ 100/μL for two consecutive observations. The following laboratory examinations are performed: * Hematology: WBC (full and differential), RBC, platelets, Hb, Htc, MCV, MPV, serology CMV (PCR and antigenemia). * Blood chemistry: AST, ALT, γGT, total bilirubin, LDH.
Time frame: Weekly up to IR after engraftment of HCT, monthly for 6 months from date of IR and then at month 9 and 12
Population: The analysis has been performed for all patients in the two treatment arms. The NRM analysis was performed on the Intention to Treat Population (ITT) and Per Protocol (PP) set populations.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| A-Experimental Arm | Immune Reconstitution (IR) | IR on ITT | Patients with immune reconstitution without previous relapse or progression | 38 Participants |
| A-Experimental Arm | Immune Reconstitution (IR) | IR on ITT | Deaths without previous immune reconstitution, relapse or progression | 13 Participants |
| A-Experimental Arm | Immune Reconstitution (IR) | IR on ITT | Patients with relapse or progression without previous immune reconstitution | 6 Participants |
| A-Experimental Arm | Immune Reconstitution (IR) | IR on ITT | Censored patients | 1 Participants |
| A-Experimental Arm | Immune Reconstitution (IR) | IR on PP Set | Patients with immune reconstitution without previous relapse or progression | 29 Participants |
| A-Experimental Arm | Immune Reconstitution (IR) | IR on PP Set | Deaths without previous immune reconstitution, relapse or progression | 4 Participants |
| A-Experimental Arm | Immune Reconstitution (IR) | IR on PP Set | Patients with relapse or progression without previous immune reconstitution | 5 Participants |
| A-Experimental Arm | Immune Reconstitution (IR) | IR on PP Set | Censored patients | 0 Participants |
| B - Control Arm | Immune Reconstitution (IR) | IR on PP Set | Censored patients | 0 Participants |
| B - Control Arm | Immune Reconstitution (IR) | IR on ITT | Patients with immune reconstitution without previous relapse or progression | 22 Participants |
| B - Control Arm | Immune Reconstitution (IR) | IR on PP Set | Patients with immune reconstitution without previous relapse or progression | 22 Participants |
| B - Control Arm | Immune Reconstitution (IR) | IR on ITT | Deaths without previous immune reconstitution, relapse or progression | 5 Participants |
| B - Control Arm | Immune Reconstitution (IR) | IR on PP Set | Patients with relapse or progression without previous immune reconstitution | 1 Participants |
| B - Control Arm | Immune Reconstitution (IR) | IR on ITT | Patients with relapse or progression without previous immune reconstitution | 1 Participants |
| B - Control Arm | Immune Reconstitution (IR) | IR on PP Set | Deaths without previous immune reconstitution, relapse or progression | 3 Participants |
| B - Control Arm | Immune Reconstitution (IR) | IR on ITT | Censored patients | 0 Participants |
Comparison: This Statistical analysis refers to Immune reconstitution and was performed by Gray's Test for Equality of Cumulative Incidence Functions for intention-To-Treat populationp-value: 0.1735Chi-squared
Comparison: This Statistical analysis refers to deaths without previous immune reconstitution, relapse or progression and was performed by Gray's Test for Equality of Cumulative Incidence Functions for intention-To-Treat populationp-value: 0.5958Chi-squared
Comparison: This Statistical Analysis refers to patients with relapse or progression without previous immune reconstitution and was performed Gray's Test for Equality of Cumulative Incidence Functionsp-value: 0.2889Chi-squared
Comparison: This Statistical analysis refers to Immune reconstitution and was performed by Gray's Test for Equality of Cumulative Incidence Functions for Per-Protocol Set.p-value: 0.1642Chi-squared
Comparison: This Statistical analysis refers to deaths without previous immune reconstitution, relapse or progression and was performed by Gray's Test for Equality of Cumulative Incidence Functions for intention-To-Treat populationp-value: 0.8739Log Rank
Comparison: This Statistical Analysis refers to patients with relapse or progression without previous immune reconstitution and was performed Gray's Test for Equality of Cumulative Incidence Functionsp-value: 0.2304Chi-squared
Secondary
Incidence and Duration of Infectious Episodes and Infectious Disease Mortality
Diagnosis, monitoring and treatment of infectious relevant events
Time frame: From randomization to the date of resolution, assessed up to 12 months
Population: Due to the early termination of the study, the analysis was not performed because data were not collected for this Outcome Measure
Secondary
Non-relapse Mortality (NRM)
Defined for all patients as any death without previous occurrence of a documented relapse (or progression). Absence of relapse was determined by the Investigator based on the following disease examination: * Morphology (bone marrow or peripheral blood) * Confirmation of mixed or full chimerism (evaluation of the degree of chimerism between donor/host, according to institutional clinical practice, on bone marrow or peripheral blood) * Cytogenetic and/or molecular and/or other tests, according to institutional clinical practice (bone marrow or peripheral blood). Gray's test was used to compare the sub-distribution functions of the death without previous relapse (or progression) and relapse (or progression) events in the two treatment groups.
Time frame: From the date of randomization to the date of death, assessed up to 12 months.
Population: The analysis has been performed for all patients in the two treatment arms. The NRM analysis was performed on the Intention to Treat Population (ITT) and Per Protocol (PP) set populations.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| A-Experimental Arm | Non-relapse Mortality (NRM) | NRM on ITT population | Deaths without previous relapse or progression | 27 Participants |
| A-Experimental Arm | Non-relapse Mortality (NRM) | NRM on ITT population | Patients with relapse or progression | 18 Participants |
| A-Experimental Arm | Non-relapse Mortality (NRM) | NRM on ITT population | Censored patients | 19 Participants |
| A-Experimental Arm | Non-relapse Mortality (NRM) | NRM on PP Set | Deaths without previous relapse or progression | 14 Participants |
| A-Experimental Arm | Non-relapse Mortality (NRM) | NRM on PP Set | Patients with relapse or progression | 11 Participants |
| A-Experimental Arm | Non-relapse Mortality (NRM) | NRM on PP Set | Censored patients | 13 Participants |
| B - Control Arm | Non-relapse Mortality (NRM) | NRM on PP Set | Patients with relapse or progression | 11 Participants |
| B - Control Arm | Non-relapse Mortality (NRM) | NRM on ITT population | Deaths without previous relapse or progression | 9 Participants |
| B - Control Arm | Non-relapse Mortality (NRM) | NRM on PP Set | Deaths without previous relapse or progression | 7 Participants |
| B - Control Arm | Non-relapse Mortality (NRM) | NRM on ITT population | Patients with relapse or progression | 11 Participants |
| B - Control Arm | Non-relapse Mortality (NRM) | NRM on PP Set | Censored patients | 8 Participants |
| B - Control Arm | Non-relapse Mortality (NRM) | NRM on ITT population | Censored patients | 8 Participants |
Comparison: This Statistical Analysis refers to ITT Deaths without previous relapse or progression and was performed with Gray's Test for Equality of Cumulative Incidence Functionsp-value: 0.4035Chi-squared
Comparison: This statistical test refers to Patients with relapse or progression and was performed to Gray's Test for Equality of Cumulative Incidence Functions.p-value: 0.3526Chi-squared
Comparison: This Statistical Analysis refers to PPS Deaths without previous relapse or progression and was performed with Gray's Test for Equality of Cumulative Incidence Functionsp-value: 0.5929Chi-squared
Comparison: This statistical test refers to Patients with relapse or progression and was performed to Gray's Test for Equality of Cumulative Incidence Functions.p-value: 0.2607Chi-squared
Secondary
Overall Survival (OS)
any death without previous occurrence of a documented relapse (or progression).Patients alive or without any follow up will be censored.
Time frame: From the date of randomization to the date of death, assessed up to 12 months
Population: TThe analysis has been performed for all patients in the two treatment arms. The NRM analysis was performed on the Intention to Treat Population (ITT) and Per Protocol (PP) set populations.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| A-Experimental Arm | Overall Survival (OS) | OS on ITT | Censored patients | 22 Participants |
| A-Experimental Arm | Overall Survival (OS) | OS on PP Set - day 21 after transplant | Deaths | 33 Participants |
| A-Experimental Arm | Overall Survival (OS) | OS on ITT | Deaths | 42 Participants |
| A-Experimental Arm | Overall Survival (OS) | OS on PP Set | Censored patients | 14 Participants |
| A-Experimental Arm | Overall Survival (OS) | OS on PP Set | Deaths | 24 Participants |
| A-Experimental Arm | Overall Survival (OS) | OS on ITT- day 21 after transplant | Censored patients | 20 Participants |
| A-Experimental Arm | Overall Survival (OS) | OS on ITT- day 21 after transplant | Deaths | 35 Participants |
| A-Experimental Arm | Overall Survival (OS) | OS on PP Set - day 21 after transplant | Censored patients | 18 Participants |
| B - Control Arm | Overall Survival (OS) | OS on PP Set - day 21 after transplant | Censored patients | 10 Participants |
| B - Control Arm | Overall Survival (OS) | OS on PP Set | Deaths | 16 Participants |
| B - Control Arm | Overall Survival (OS) | OS on PP Set - day 21 after transplant | Deaths | 18 Participants |
| B - Control Arm | Overall Survival (OS) | OS on ITT | Censored patients | 10 Participants |
| B - Control Arm | Overall Survival (OS) | OS on ITT- day 21 after transplant | Deaths | 18 Participants |
| B - Control Arm | Overall Survival (OS) | OS on ITT | Deaths | 18 Participants |
| B - Control Arm | Overall Survival (OS) | OS on ITT- day 21 after transplant | Censored patients | 10 Participants |
| B - Control Arm | Overall Survival (OS) | OS on PP Set | Censored patients | 10 Participants |
p-value: 0.766Log Rank
Comparison: Statistical analysis has been performed for Intention-To-Treat population.p-value: 0.6706Wilcoxon (Mann-Whitney)
Comparison: Statistical analysis has been performed for Per-Protocol Set)p-value: 0.7332Log Rank
Comparison: Statistical analysis has been performed for Per-Protocol Set)p-value: 0.6439Wilcoxon (Mann-Whitney)
Secondary
Quality of Life (QoL) and Medical Care Utilization (MCU) in Both Arms
Medical resource use data collected will be used in health economic analyses where it may be combined with other data from other sources such as cost data or other clinical parameters.
Time frame: from randomization up to 12 months
Population: Due to the early termination of the study, the analysis was not performed because data were not collected for this Outcome Measure