Hematologic MalignancyPhase 2NCT03717480
Ex Vivo TCR αβ T Cell Depletion for Graft-Versus-Host Disease Prophylaxis in Mismatched Donor Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies
A Phase 2 study testing ClinicMACs in people with Hematologic Malignancy, run by Dana-Farber Cancer Institute at 1 site in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hematologic Malignancy
- What is being tested?
- ClinicMACs
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Jan 2020to 26 Apr 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Show all 13Show fewer
- --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
Trial locations and contacts
1 site in 1 country.
United States1 site
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
About this study
Official title: A Phase 2 Study of Ex Vivo TCR αβ T Cell Depletion for Graft-Versus-Host Disease (GVHD) Prophylaxis in Mismatched Donor Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies
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
Read the 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
- Conditions
- Hematologic Malignancy
- Being tested
- ClinicMACs
- Keywords
- Graft vs. Host Disease, Hematologic Malignancy
- Medical subject headings
- Hematologic Neoplasms, Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClinicMACsDevice
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
| Study group | Role | What they receive |
|---|---|---|
| TCR α/β Reagent System | Experimental | * The stem cell apheresis product will be depleted of TCRαβ T cells by negative selection using the automated CliniMACS® Plus device.
* CD34+ stem cell counts will be obtained before and after processing with the Miltenyi ClinicMACs device Receives: Device: ClinicMACs |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 100 Days
Secondary outcomes (11)
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.
Measured: 2 years
Number of Participants With Chronic GVHD
Number of participants with chronic GVHD will be assessed at 2 years post-SCT.
Measured: 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.
Measured: 2 years
Number of Participants With Immunosuppression-free Survival
Number of participants with immunosuppression-free survival will be assessed at 2 years post-SCT.
Measured: 2 years
Number of Participants With Hematologic Recovery
Hematologic recovery will be assessed in participants at 2 years post-SCT.
Measured: 2 years
Number of Participants With Immune Reconstitution
Immune reconstitution will be assessed in participants at 2 years post-SCT.
Measured: 2 years
Number of Participants With Disease Relapse
Disease relapse will be assessed in participants at 2 years post-SCT.
Measured: 2 years
Number of Participants With Transplant-related Mortality
Participant transplant-related mortality will be assessed at 2 years post-SCT.
Measured: 2 years
Number of Participants With Organ Toxicity
Participant organ toxicity will be assessed at 2 years post-SCT.
Measured: 2 years
Rates of Infections
Participant rate of infections will be assessed at 2 years post-SCT.
Measured: 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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2018
- Study start21 Jan 2020
- Primary completion26 Apr 2021
- Study completion26 Apr 2021
Why it stopped: 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.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hematologic MalignancyStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Vincent T. Ho, MD, Dana-Farber Cancer Institute
- Investigators
- Vincent T Ho, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03717480
- Sponsor's protocol ID
- 18-270
- Status last verified
- Apr 2022
- First submitted
- 22 Oct 2018
- Last updated
- 10 May 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Ex Vivo TCR αβ T Cell Depletion for Graft-Versus-Host Disease (GVHD) Prophylaxis in Mismatched Donor Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT03717480
- Acronym / sponsor ID
- 18-270
- Conditions
- Hematologic Malignancy
- Keywords
- Graft vs. Host Disease, Hematologic Malignancy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: 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.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Study start
- 21 Jan 2020 (actual)
- Primary completion
- 26 Apr 2021 (actual)
- Study completion
- 26 Apr 2021 (actual)
- First posted
- 24 Oct 2018 (actual)
- Results
- Posted 10 May 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TCR α/β Reagent System | Experimental | Device: ClinicMACs* The stem cell apheresis product will be depleted of TCRαβ T cells by negative selection using the automated CliniMACS® Plus device. * CD34+ stem cell counts will be obtained before and after processing with the Miltenyi ClinicMACs device |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (13 listed)
- 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%
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ClinicMACsThe 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 | Device | TCR α/β Reagent System |
Primary outcome
Number of Participants With Severe Acute GVHD-free Survival
Time frame: 100 Days
Number of participants with severe acute GVHD-free survival will be assessed at 100 days post-SCT
11 secondary outcomes
Number of Participants With Grades II-IV Acute GVHD
Time frame: 2 years
Number of Participants With Chronic GVHD
Time frame: 2 years
Number of Participants With GVHD and Relapse Free Survival (GRFS)
Time frame: 2 years
Number of Participants With Immunosuppression-free Survival
Time frame: 2 years
Number of Participants With Hematologic Recovery
Time frame: 2 years
Number of Participants With Immune Reconstitution
Time frame: 2 years
Number of Participants With Disease Relapse
Time frame: 2 years
Number of Participants With Transplant-related Mortality
Time frame: 2 years
Number of Participants With Organ Toxicity
Time frame: 2 years
Rates of Infections
Time frame: 2 years
Number of Participants With Relapse-free and Overall Survival
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vincent T Ho, MD principal investigator
Dana-Farber Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ClinicMACs in people with Hematologic Malignancy, run by Dana-Farber Cancer Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Severe Acute GVHD-free Survival (time frame: 100 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2022.