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The study was prematurely closed to enrollment due to feasibility issues, as the site has promising upcoming competing trials, and the study was already not enrolling at a rate sufficient to meet the accrual goal.
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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
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:
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TCR α/β Reagent System | Experimental |
|
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ClinicMACs | Device | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 100 Days |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Diagnoses and stage at time of transplant admission:
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
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| Name | Affiliation | Role |
|---|---|---|
| Vincent T Ho, MD | Dana-Farber Cancer Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dana Farber Cancer Institute | Boston | Massachusetts | 02215 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | ||||
|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 8, 2017 |
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| 2 years |
| Number of Participants With Chronic GVHD | Number of participants with chronic GVHD will be assessed at 2 years post-SCT. | 2 years |
| 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. | 2 years |
| Number of Participants With Immunosuppression-free Survival | Number of participants with immunosuppression-free survival will be assessed at 2 years post-SCT. | 2 years |
| Number of Participants With Hematologic Recovery | Hematologic recovery will be assessed in participants at 2 years post-SCT. | 2 years |
| Number of Participants With Immune Reconstitution | Immune reconstitution will be assessed in participants at 2 years post-SCT. | 2 years |
| Number of Participants With Disease Relapse | Disease relapse will be assessed in participants at 2 years post-SCT. | 2 years |
| Number of Participants With Transplant-related Mortality | Participant transplant-related mortality will be assessed at 2 years post-SCT. | 2 years |
| Number of Participants With Organ Toxicity | Participant organ toxicity will be assessed at 2 years post-SCT. | 2 years |
| Rates of Infections | Participant rate of infections will be assessed at 2 years post-SCT. | 2 years |
| 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. | 2 years |
|
| Receipt of Investigational Product/Study Treatment |
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| COMPLETED | Survival to day 100 for evaluation of primary endpoint (severe acute GVHD-free survival rate) |
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| NOT COMPLETED |
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Only evaluable participants, defined as participants who received investigational product, are included in the analysis population. Therefore, participants who never started protocol treatment have been excluded.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | Posted | Count of Participants | Participants | 100 Days |
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| |||||||||||||||||||||||||||
| 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. | 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. | Posted | 2 years |
|
| |||||||||||||||||||||||||||||
| Secondary | Number of Participants With Chronic GVHD | Number of participants with chronic GVHD will be assessed at 2 years post-SCT. | 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. | Posted | 2 years |
|
| |||||||||||||||||||||||||||||
| 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. | 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. | Posted | 2 years |
|
| |||||||||||||||||||||||||||||
| Secondary | Number of Participants With Immunosuppression-free Survival | Number of participants with immunosuppression-free survival will be assessed at 2 years post-SCT. | 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. | Posted | 2 years |
|
| |||||||||||||||||||||||||||||
| Secondary | Number of Participants With Hematologic Recovery | Hematologic recovery will be assessed in participants at 2 years post-SCT. | 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. | Posted | 2 years |
|
| |||||||||||||||||||||||||||||
| Secondary | Number of Participants With Immune Reconstitution | Immune reconstitution will be assessed in participants at 2 years post-SCT. | 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. | Posted | 2 years |
|
| |||||||||||||||||||||||||||||
| Secondary | Number of Participants With Disease Relapse | Disease relapse will be assessed in participants at 2 years post-SCT. | 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. | Posted | 2 years |
|
| |||||||||||||||||||||||||||||
| Secondary | Number of Participants With Transplant-related Mortality | Participant transplant-related mortality will be assessed at 2 years post-SCT. | 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. | Posted | 2 years |
|
| |||||||||||||||||||||||||||||
| Secondary | Number of Participants With Organ Toxicity | Participant organ toxicity will be assessed at 2 years post-SCT. | 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. | Posted | 2 years |
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| Secondary | Rates of Infections | Participant rate of infections will be assessed at 2 years post-SCT. | 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. | Posted | 2 years |
|
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| 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. | 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. | Posted | 2 years |
|
|
Adverse event data was collected for each participant up until 2 years post-transplant or until the participant's death, whichever came first. The only participant who received study treatment did not survive to the analysis timepoint of 2 years post-transplant, so all documented adverse events were collected from the date of their transplant up until their death approximately 9 months post-transplant.
Adverse events were collected through regular investigator assessment and laboratory testing.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 | 1 | 1 | 1 | 1 | 1 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hepatic Hemorrhage | Hepatobiliary disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Colonic Perforation | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Platelet Count Decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Respiratory Failure | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Acute Kidney Injury | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Stroke | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment | Adenovirus |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal Pain | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Alanine Aminotransferase Increased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Anorexia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
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| Aspartate Aminotransferase Increased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Bacteremia | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Creatinine Increased | Investigations | CTCAE (4.0) | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Dizziness | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Fatigue | General disorders | CTCAE (4.0) | Systematic Assessment |
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| Hematuria | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
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| Insomnia | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
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| Infections and Infestations - Other, specify | Infections and infestations | CTCAE (4.0) | Systematic Assessment | EBV+ |
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| Mucositis Oral | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Platelet Count Decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
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| Rash Maculo-papular | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
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| Vaginal Pain | Reproductive system and breast disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Weight Loss | Investigations | CTCAE (4.0) | Systematic Assessment |
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| White Blood Cell Decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
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Early termination after accrual of only one evaluable subject resulted in an insufficient sample size for analysis.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Vincent Ho | Dana-Farber Cancer Institute | 617-632-6256 | vincent_ho@dfci.harvard.edu |
| Feb 22, 2022 |
| Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D019337 | Hematologic Neoplasms |
| D006086 | Graft vs Host Disease |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007154 | Immune System Diseases |
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| Unknown or Not Reported |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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