Malignant Diseases, Non-malignant Diseases
Conditions
Keywords
Haplocompatible, Stem cell transplant, Borderline organ function, Alternative donor stem cell transplant
Brief summary
The purpose of this protocol is to provide access to the CliniMACS® System to hematopoietic cell transplant (HSCT) patients who do not have a matched related donor. The CliniMACS system is currently approved for use in patients who have AML, and a genetically matched sibling donor. Through this protocol, the investigators will be able to offer potentially life-saving transplants to patients who have genetically mis-matched donor, who have no other options for treatment.
Interventions
DEVICECliniMACS CD34+ cell enrichment and T-cell depletion
Sponsors
Rajni Agarwal
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 35 Years
Healthy volunteers
No
Inclusion criteria
* Participant age is 0 (newborn) to 35 years-old. * Participant has a disorder affecting the hematopoietic system that are inherited, acquired, or a result from the myeloablative treatment that can benefit from alternative stem cell transplantation according to standard practice guidelines for including patients for transplant. * Participant's medical screening clears s/he for allogeneic transplantation as per current institutional SOP based on standards of foundation for accreditation of cellular therapy and stem cell transplantation (FACT); * Participant must lack a healthy, HLA-identical related or unrelated donor unless s/he has a borderline organ function that will preclude the recipient from receiving a curative therapy due to the need of post-HSCT immunosuppressive therapy. * Participant must have a matched or mismatched-related donor who is: * Able to receive granulocyte colony-stimulating factor (G-CSF) and undergo apheresis either through placement of catheters in antecubital veins or a temporary central venous catheter OR agrees on a bone marrow harvest; * Healthy as per donor selection screening (following current SOP based on standards of foundation for accreditation of cellular therapy and stem cell transplantation - FACT); * Willing to participate and sign consent. * Participant or Legal Authorized Representative is able to sign informed consent (and signed assent, if applicable) for transplant.
Exclusion criteria
* Participant does not qualify for an allogeneic transplant due to medical screening, underlying disease, or lack of alternative donors. * Any condition that compromises compliance with the procedures of this protocol, as judged by the principal investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Severe (Grade III/IV) Acute Graft vs Host Disease (GVHD) | Day +100 | GVHD is a condition that occurs when donor bone marrow or stem cells attack the recipient. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Graft Failure | Up to Day +42 after stem cell transplant | Failure of donor stem cells to make neutrophils |
| Length of Time to Engraftment | up to +1 year post-transplant | Absolute neutrophil count (ANC) \>500 for 3 consecutive days and \>80% donor cells in blood. |
| Chimerism of Donor Cells | Day +100 post-transplant | The percentage of donor cells for all evaluable (without disease progression) patients |
| Immune Recovery (CD4) | up to +1 year post-transplant | The time to CD4 count \>100 |
| Number of Participants With Immune Recovery (CD4 >200) by Year 1 | up to +1 year post-transplant | — |
| Immune Recovery Shown as Phytohemagglutin (PHA) | 6 months and 1 year post-transplant | Immune recovery defined as achieving normal levels of PHA (53,000-200,000 CPM) |
| Number of Patients With Post-transplant Lymphoproliferative Disease (PTLD) | up to +1 year post-transplant | Post-transplant lymphoproliferative disorder (PTLD) is a well-known, life-threatening complication of organ transplantation, predominantly occurring after solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT). |
| Number of Patients With Severe Toxicities | up to +1 year post-transplant | Incidence of transplant-related toxicities |
| Number of Participants Experiencing Post-transplant Infections | up to +1 year post-transplant | Post-transplant infections will be described by incidence and type. Participants may have had more than one type of infection. |
| Transplant-related Mortality (TRM) | at Day +100 and +1 year post-transplant | Death related to transplant |
Countries
United States
Participant flow
Recruitment details
Enrollment was open to participants with malignant or non-malignant disorders receiving mismatched related donor hematopoietic stem cell transplants who could benefit from augmented CD34+ cells and T cell-depleted products to prevent severe (grade III/IV) acute Graft vs Host Disease (GVHD). Participants were withdrawn from the study at the time of graft failure due to need for exclusionary concurrent treatment (per PI discretion)
Participants by arm
| Arm | Count |
|---|---|
| ARM A Malignant TBI Malignant diseases Conditioning including total body irradiation and chemotherapy
CliniMACS CD34+ cell enrichment and T-cell depletion | 0 |
| ARM B Malignant Non-TBI Malignant diseases chemotherapy based conditioning
CliniMACS CD34+ cell enrichment and T-cell depletion | 0 |
| ARM C Non-malignant Non-malignant diseases Chemotherapy based conditioning
CliniMACS CD34+ cell enrichment and T-cell depletion | 3 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lack of Efficacy | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | ARM A Malignant TBI | ARM B Malignant Non-TBI | ARM C Non-malignant | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 3 Participants | 3 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | — | — | 7.47 years | 7.47 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | — | — | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | — | — | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | — | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | — | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | — | — | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | — | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | — | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | — | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | — | — | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | — | — | 0 Participants | 0 Participants |
| Region of Enrollment United States | — | — | 3 Participants | 3 Participants |
| Sex: Female, Male Female | — | — | 1 Participants | 1 Participants |
| Sex: Female, Male Male | — | — | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 3 |
| other Total, other adverse events | 0 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
Number of Patients With Severe (Grade III/IV) Acute Graft vs Host Disease (GVHD)
GVHD is a condition that occurs when donor bone marrow or stem cells attack the recipient.
Time frame: Day +100
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ARM C Non-malignant | Number of Patients With Severe (Grade III/IV) Acute Graft vs Host Disease (GVHD) | 0 Participants |
Secondary
Chimerism of Donor Cells
The percentage of donor cells for all evaluable (without disease progression) patients
Time frame: Day +100 post-transplant
Population: Patients who had primary graft failure were withdrawn from the study are excluded from the analysis.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| ARM C Non-malignant | Chimerism of Donor Cells | Whole Blood | 95 Percentage of cells from donor |
| ARM C Non-malignant | Chimerism of Donor Cells | CD3 Cells | 70 Percentage of cells from donor |
| ARM C Non-malignant | Chimerism of Donor Cells | CD15 Cells | 100 Percentage of cells from donor |
| ARM C Non-malignant | Chimerism of Donor Cells | CD19 | 99 Percentage of cells from donor |
| ARM C Non-malignant | Chimerism of Donor Cells | CD34 | 98 Percentage of cells from donor |
| ARM C Non-malignant | Chimerism of Donor Cells | CD56 | 99 Percentage of cells from donor |
Secondary
Immune Recovery (CD4)
The time to CD4 count \>100
Time frame: up to +1 year post-transplant
Population: Patients who had primary graft failure and were withdrawn from the study are excluded from the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| ARM C Non-malignant | Immune Recovery (CD4) | 148 days |
Secondary
Immune Recovery Shown as Phytohemagglutin (PHA)
Immune recovery defined as achieving normal levels of PHA (53,000-200,000 CPM)
Time frame: 6 months and 1 year post-transplant
Population: Participants who had primary graft failure were withdrawn from the study and unable to be evaluated for this outcome measure.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| ARM C Non-malignant | Immune Recovery Shown as Phytohemagglutin (PHA) | 6 months | 33736 Net CPM |
| ARM C Non-malignant | Immune Recovery Shown as Phytohemagglutin (PHA) | 1 year | 110809 Net CPM |
Secondary
Length of Time to Engraftment
Absolute neutrophil count (ANC) \>500 for 3 consecutive days and \>80% donor cells in blood.
Time frame: up to +1 year post-transplant
Population: Patients who had primary graft failure were withdrawn from the study are excluded from the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| ARM C Non-malignant | Length of Time to Engraftment | 10 days |
Secondary
Number of Participants Experiencing Post-transplant Infections
Post-transplant infections will be described by incidence and type. Participants may have had more than one type of infection.
Time frame: up to +1 year post-transplant
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ARM C Non-malignant | Number of Participants Experiencing Post-transplant Infections | BK viremia | 1 Participants |
| ARM C Non-malignant | Number of Participants Experiencing Post-transplant Infections | BK viruria | 1 Participants |
| ARM C Non-malignant | Number of Participants Experiencing Post-transplant Infections | Norovirus | 1 Participants |
| ARM C Non-malignant | Number of Participants Experiencing Post-transplant Infections | HHV6 viremia | 2 Participants |
| ARM C Non-malignant | Number of Participants Experiencing Post-transplant Infections | EBV viremia | 1 Participants |
| ARM C Non-malignant | Number of Participants Experiencing Post-transplant Infections | Rhinovirus/Enterovirus | 1 Participants |
| ARM C Non-malignant | Number of Participants Experiencing Post-transplant Infections | Parainfluenza 3 upper respiratory infection | 1 Participants |
| ARM C Non-malignant | Number of Participants Experiencing Post-transplant Infections | Adenovirus (low level reactivation) | 1 Participants |
| ARM C Non-malignant | Number of Participants Experiencing Post-transplant Infections | Cytomegalovirus (low level reactivation) | 1 Participants |
Secondary
Number of Participants With Graft Failure
Failure of donor stem cells to make neutrophils
Time frame: Up to Day +42 after stem cell transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ARM C Non-malignant | Number of Participants With Graft Failure | 2 Participants |
Secondary
Number of Participants With Immune Recovery (CD4 >200) by Year 1
Time frame: up to +1 year post-transplant
Population: Patients who had primary graft failure and were withdrawn from the study are excluded from the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ARM C Non-malignant | Number of Participants With Immune Recovery (CD4 >200) by Year 1 | 0 Participants |
Secondary
Number of Patients With Post-transplant Lymphoproliferative Disease (PTLD)
Post-transplant lymphoproliferative disorder (PTLD) is a well-known, life-threatening complication of organ transplantation, predominantly occurring after solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT).
Time frame: up to +1 year post-transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ARM C Non-malignant | Number of Patients With Post-transplant Lymphoproliferative Disease (PTLD) | 0 Participants |
Secondary
Number of Patients With Severe Toxicities
Incidence of transplant-related toxicities
Time frame: up to +1 year post-transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ARM C Non-malignant | Number of Patients With Severe Toxicities | 2 Participants |
Secondary
Transplant-related Mortality (TRM)
Death related to transplant
Time frame: at Day +100 and +1 year post-transplant
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ARM C Non-malignant | Transplant-related Mortality (TRM) | Day 100 | 1 Participants |
| ARM C Non-malignant | Transplant-related Mortality (TRM) | Between Day 100 and 1 Year | 1 Participants |