Hematologic Malignancies
Conditions
Keywords
hematologic malignancies (excluding Chronic Myeloid Leukemia)
Brief summary
The purpose of the Phase IIA study are to: 1. define the safety profile 2. evaluate the efficacy of a sequential infusion of unmanipulated Donor Lymphocyte Infusions (DLI) and Cytokine Induced Killer (CIK) cells for the treatment of molecular, cytogenetic or hematologic relapse after hematopoietic stem cell transplantation and The progression free survival and the overall survival after the sequential infusion of Donor Lymphocyte Infusions (DLI) and Cytokine Induced Killer(CIK) cells.
Detailed description
This study is an open-label, multicenter, exploratory phase IIA study to evaluate the safety (dose-finding) and efficacy of a sequential administration of donor derived unmanipulated DLI and in vitro expanded Cytokine Induced Killer(CIK) cells. Two infusions of unmanipulated donor lymphocytes (1x106/Kg each) will be given with a minimum interval of 3 weeks. Three infusions of donor Cytokine Induced Killer (CIK) cells will be administered according to a dose escalating program, starting 3 weeks after second Donor Lymphocyte Infusions (DLI). In presence of grade 2 or more acute graft versus host disease(GVHD), the patient will not receive the next scheduled infusion. Only grade 4 acute graft versus host disease (aGVHD) is considered for the dose limiting toxicity (DLT). Once identified the maximally tolerated dose (MTD), this same combination of doses will be administered up to 24 patients in a two-stage minimax design. Primary Endpoints The primary endpoints of the Phase IIA study are: 1. the Maximally Tolerated Dose (MTD) - (safety end-point) 2. the cumulative incidence of molecular, karyotypic or haematologic responses at day +100 after the end of the cell therapy program - (efficacy end-point) Secondary Endpoints Progression Free Survival (PFS) Progression Free Survival (PFS) will be defined as any evidence of molecular, cytogenetic or haematologic disease progression. Cytogenetic and/or molecular relapse will be defined where available as any evidence of a pre-transplant defined abnormality using conventional cytogenetics or FISH techniques or molecular probes. Assessments will be performed at 1 year after the end of the cell therapy program Overall Survival (OS) The Overall Survival(OS) will be assessed by 1 year after the end of the cell therapy program. For assessment of the Overall Survival (OS), events will be deaths for any causes, patients being censored if alive.
Interventions
BIOLOGICALin vitro expanded Cytokine Induced Killer (CIK) cells
Three infusions of donor Cytokine Induced Killer (CIK) cells will be administered according to a dose escalating program, starting 3 weeks after second Donor Lymphocyte Infusions (DLI). Cytokine Induced Killer administrations will be separated by 3 weeks intervals
Sponsors
Regional Hospital of Bolzano
Azienda Ospedaliera San Gerardo di Monza
A.O. Ospedale Papa Giovanni XXIII
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients with haematologic malignancies (excluding chronic myeloid Leukemia- CML) with a molecular, cytogenetic or haematologic relapse after allogeneic transplantation. * Patients with an available donor willing to donate peripheral blood lymphocytes * Immunosuppression must be withdrawn at the beginning of the cell therapy program * Written informed consent prior to any study procedures being performed
Exclusion criteria
* Donors positive for HIV, HBV or HCV, or unfit to undergo leukapheresis * Patients with active acute or chronic Graft versus host disease (GvHD) * Patients with rapidly progressive disease or not controlled by palliative supportive treatments including chemotherapy and with a life expectancy less than 8 weeks * Patients with severe psychiatric illness or any disorder that compromises ability to give truly informed consent for participation in this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Measures | Clinical response was measured at 100 days after the completion of the cell therapy program. | The occurrence of a grade 4 acute graft versus host disease (GVHD), judged to be related to the study medication. Grading and staging will be performed using the Glucksberg scale |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy Measures | The clinical response will be registered at day +100 after the last Cytokine Induced Killer (CIK) cell infusion | The proportion of patients achieving a complete, a partial or a hematologic improvement in responses to the experimental infusion of cytokine induced killer (CIK)cells |
Countries
Italy
Participant flow
Recruitment details
A total of 74 patients were enrolled in the study from July 2009 to September 2016
Participants by arm
| Arm | Count |
|---|---|
| Cytokine Induced Killer Sequential Infusion of Unmanipulated Donor Lymphocytes and Cytokine Induced Killer (CIK)
in vitro expanded Cytokine Induced Killer (CIK) cells: Three infusions of donor Cytokine Induced Killer (CIK) cells will be administered according to a dose escalating program, starting 3 weeks after second Donor Lymphocyte Infusions (DLI). Cytokine Induced Killer administrations will be separated by 3 weeks intervals | 73 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 30 |
Baseline characteristics
| Characteristic | Cytokine Induced Killer |
|---|---|
| Age, Categorical <=18 years | 15 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 58 Participants |
| Region of Enrollment Italy | 73 participants |
| Sex: Female, Male Female | 34 Participants |
| Sex: Female, Male Male | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 31 / 73 |
| other Total, other adverse events | 16 / 73 |
| serious Total, serious adverse events | 8 / 73 |
Outcome results
Primary
Safety Measures
The occurrence of a grade 4 acute graft versus host disease (GVHD), judged to be related to the study medication. Grading and staging will be performed using the Glucksberg scale
Time frame: Clinical response was measured at 100 days after the completion of the cell therapy program.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cytokine Induced Killer | Safety Measures | 0 participants |
Secondary
Efficacy Measures
The proportion of patients achieving a complete, a partial or a hematologic improvement in responses to the experimental infusion of cytokine induced killer (CIK)cells
Time frame: The clinical response will be registered at day +100 after the last Cytokine Induced Killer (CIK) cell infusion