Hematologic Malignancy
Conditions
Keywords
Graft vs. Host Disease, Hematologic Malignancy
Brief summary
This research study is studying the removal of a subset of white blood cells (called alpha/beta T cells) from the donor product using a cell separation device before the product is transplanted into the participant. The device used to remove the α/βT cells in this study is: -CliniMACS® TCR α/β Reagent System
Detailed description
Patients who receive an allogeneic (using another person as the donor) stem cell transplant (SCT) are at risk for developing graft-versus-host disease (GVHD). The word graft refers to the donor blood cells that you will receive during the transplant. The word host refers to the person receiving the cells. GVHD is a complication of transplantation where the donor graft attacks and damages some of the participant's tissues. GVHD may occur when the T cells (a type of white blood cell that helps protect the body from infection) from the donor react against normal tissues or organs in the body. There are two basic types of GVHD: * Acute GVHD often occurs early (generally first 3-6 months after SCT) may affect skin, gastrointestinal tract (stomach and intestines) and liver. * Chronic GVHD often occurs later (Usually after 3-6 months after SCT) and may affect many organs and significantly diminish quality of life. To confirm the diagnosis of acute or chronic GVHD, the participant may be asked to have a biopsy (a small sample of the participant's tissue to look at under the microscope) of the skin, gut, or, rarely, the liver. In this research study, the investigator are investigating a pre-transplant intervention aimed to prevent GVHD by processing the donor product with the Miltenyi CliniMACS TCR α/β Reagent System. The Reagent System will remove certain cells (called T-Cell Receptor (TCR) α/β positive T-cells) that are thought to cause GVHD from donor product before it is given to the participant. By selectively removing this specific type of T cells from the donor product, the investigators hope to reduce the risk for GVHD without reducing the efficacy of the transplant. This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. Investigational means that the intervention is being studied. The FDA (the U.S. Food and Drug Administration) has not approved CliniMACS α/β T cell depletion system for use in the US, but this system is approved by the European Medicines Agency (EMA) and used in Europe
Interventions
DEVICEClinicMACs
The Reagent System will remove certain cells (called T-Cell Receptor (TCR) α/β positive T-cells) that are thought to cause GVHD from donor product before it is given to participants
Sponsors
Dana-Farber Cancer Institute
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
* Diagnoses and stage at time of transplant admission: * Acute leukemia (AML or ALL or MPAL) in first or subsequent remission * Myelodysplastic syndromes (MDS) with \<10% marrow blasts * Myeloproliferative neoplasm (MPN) with \<10% marrow blasts * CMML with less than 10% marrow blast * CML accelerated phase or second or subsequent chronic phase * Non-Hodgkin's lymphoma in PR or CR2 or beyond * Hodgkin lymphoma in PR or CR2 or beyond * Age 18-65 years * Patient has a related or unrelated donor who is 8 or 9 out of 10 match at HLA A, B, C, DRB1 and DQB1, based on allele level typing. * Patient ECOG performance status 0-2 (Karnofsky ≥60%, see Appendix A) * Patient deemed to be appropriate candidate for myeloablative conditioning transplantation. * Ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
* Patient with active HIV infection * Chronic active hepatitis B infection (HepB surface Ag+ or detectable Hep B viral load) * Prior allogeneic hematopoietic stem cell transplantation * Impaired cardiac function- ejection fraction \< 40% * Impaired pulmonary function- pretransplant FEV1, DLCO \< 50% * Impaired renal function, based on --Serum creatinine \> 2.0 mg/dl * Impaired liver function unrelated to primary disease, based on --ALT or AST \> 3x ULN, or Total Bilirubin \> 2.0mg/dl (with exception for known or suspected Gilbert's disease) * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Women who are pregnant or breast feeding. Women of child bearing potential must have a negative serum pregnancy test at study entry. * Participants who are receiving any other investigational agents are eligible but such agent must be discontinued before admission for HSCT, and if resumption of investigation agent is planned after HSCT, this must be approved by the study PI. * Participants with known active CNS disease. CNS disease that has been treated is eligible
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Severe Acute GVHD-free Survival | 100 Days | Number of participants with severe acute GVHD-free survival will be assessed at 100 days post-SCT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Chronic GVHD | 2 years | Number of participants with chronic GVHD will be assessed at 2 years post-SCT. |
| Number of Participants With GVHD and Relapse Free Survival (GRFS) | 2 years | GRFS will be defined as alive without having experienced grade III-IV acute GVHD, moderate/severe chronic GVHD, or relapse of underlying malignancy. |
| Number of Participants With Immunosuppression-free Survival | 2 years | Number of participants with immunosuppression-free survival will be assessed at 2 years post-SCT. |
| Number of Participants With Hematologic Recovery | 2 years | Hematologic recovery will be assessed in participants at 2 years post-SCT. |
| Number of Participants With Immune Reconstitution | 2 years | Immune reconstitution will be assessed in participants at 2 years post-SCT. |
| Number of Participants With Grades II-IV Acute GVHD | 2 years | Grades II-IV acute GVHD will be assessed at 2 years post-SCT. Grade I GVHD is characterized as mild disease, grade II as moderate, grade III as severe, and grade IV as life-threatening. Higher grades of acute GVHD are associated with worse outcomes. Acute GVHD will be staged by assessment of clinical manifestations in the skin, gastrointestinal tract, and liver. |
| Number of Participants With Transplant-related Mortality | 2 years | Participant transplant-related mortality will be assessed at 2 years post-SCT. |
| Number of Participants With Organ Toxicity | 2 years | Participant organ toxicity will be assessed at 2 years post-SCT. |
| Rates of Infections | 2 years | Participant rate of infections will be assessed at 2 years post-SCT. |
| Number of Participants With Relapse-free and Overall Survival | 2 years | Number of participants with relapse-free and overall survival will be assessed at 2 years post-SCT. |
| Number of Participants With Disease Relapse | 2 years | Disease relapse will be assessed in participants at 2 years post-SCT. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TCR α/β Reagent System The stem cell apheresis product was depleted of TCRαβ T cells by negative selection using the automated CliniMACS® Plus device.
CD34+ stem cell counts were obtained before and after processing with the Miltenyi ClinicMACs device.
ClinicMACs: The Reagent System removed certain cells (called T-Cell Receptor (TCR) α/β positive T-cells) that are thought to cause GVHD from donor product before it was given to participants. | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Never received investigational product due to product viability limitations. | 1 |
Baseline characteristics
| Characteristic | TCR α/β Reagent System |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 1 |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 1 / 1 |
Outcome results
Primary
Number of Participants With Severe Acute GVHD-free Survival
Number of participants with severe acute GVHD-free survival will be assessed at 100 days post-SCT
Time frame: 100 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TCR α/β Reagent System | Number of Participants With Severe Acute GVHD-free Survival | 1 Participants |
Secondary
Number of Participants With Chronic GVHD
Number of participants with chronic GVHD will be assessed at 2 years post-SCT.
Time frame: 2 years
Population: No participants were analyzed for this secondary outcome measure, because the only participant who would have been evaluable for analysis did not survive to the analysis timepoint of 2 years post-transplant.
Secondary
Number of Participants With Disease Relapse
Disease relapse will be assessed in participants at 2 years post-SCT.
Time frame: 2 years
Population: No participants were analyzed for this secondary outcome measure, because the only participant who would have been evaluable for analysis did not survive to the analysis timepoint of 2 years post-transplant.
Secondary
Number of Participants With Grades II-IV Acute GVHD
Grades II-IV acute GVHD will be assessed at 2 years post-SCT. Grade I GVHD is characterized as mild disease, grade II as moderate, grade III as severe, and grade IV as life-threatening. Higher grades of acute GVHD are associated with worse outcomes. Acute GVHD will be staged by assessment of clinical manifestations in the skin, gastrointestinal tract, and liver.
Time frame: 2 years
Population: No participants were analyzed for this secondary outcome measure, because the only participant who would have been evaluable for analysis did not survive to the analysis timepoint of 2 years post-transplant.
Secondary
Number of Participants With GVHD and Relapse Free Survival (GRFS)
GRFS will be defined as alive without having experienced grade III-IV acute GVHD, moderate/severe chronic GVHD, or relapse of underlying malignancy.
Time frame: 2 years
Population: No participants were analyzed for this secondary outcome measure, because the only participant who would have been evaluable for analysis did not survive to the analysis timepoint of 2 years post-transplant.
Secondary
Number of Participants With Hematologic Recovery
Hematologic recovery will be assessed in participants at 2 years post-SCT.
Time frame: 2 years
Population: No participants were analyzed for this secondary outcome measure, because the only participant who would have been evaluable for analysis did not survive to the analysis timepoint of 2 years post-transplant.
Secondary
Number of Participants With Immune Reconstitution
Immune reconstitution will be assessed in participants at 2 years post-SCT.
Time frame: 2 years
Population: No participants were analyzed for this secondary outcome measure, because the only participant who would have been evaluable for analysis did not survive to the analysis timepoint of 2 years post-transplant.
Secondary
Number of Participants With Immunosuppression-free Survival
Number of participants with immunosuppression-free survival will be assessed at 2 years post-SCT.
Time frame: 2 years
Population: No participants were analyzed for this secondary outcome measure, because the only participant who would have been evaluable for analysis did not survive to the analysis timepoint of 2 years post-transplant.
Secondary
Number of Participants With Organ Toxicity
Participant organ toxicity will be assessed at 2 years post-SCT.
Time frame: 2 years
Population: No participants were analyzed for this secondary outcome measure, because the only participant who would have been evaluable for analysis did not survive to the analysis timepoint of 2 years post-transplant.
Secondary
Number of Participants With Relapse-free and Overall Survival
Number of participants with relapse-free and overall survival will be assessed at 2 years post-SCT.
Time frame: 2 years
Population: No participants were analyzed for this secondary outcome measure, because the only participant who would have been evaluable for analysis did not survive to the analysis timepoint of 2 years post-transplant.
Secondary
Number of Participants With Transplant-related Mortality
Participant transplant-related mortality will be assessed at 2 years post-SCT.
Time frame: 2 years
Population: No participants were analyzed for this secondary outcome measure, because the only participant who would have been evaluable for analysis did not survive to the analysis timepoint of 2 years post-transplant.
Secondary
Rates of Infections
Participant rate of infections will be assessed at 2 years post-SCT.
Time frame: 2 years
Population: No participants were analyzed for this secondary outcome measure, because the only participant who would have been evaluable for analysis did not survive to the analysis timepoint of 2 years post-transplant.