Bone Marrow Transplant InfectionNCT04687982
Feasibility and Efficacy of Modified Donor Lymphocytes Infusion (CD45RA Negative Selected) After Haploidentical Transplantation With Post-transplantation Cyclophosphamide in Patients With Hematological Malignancies (ONC-2016-002).
A study testing modified donor lymphocytes infusion (mDLI) in people with Bone Marrow Transplant Infection and Bone Marrow Transplant Complications, run by Istituto Clinico Humanitas at 1 site in Italy.
Trial summary
Interventional non-randomized trial. The duration of study will be 47 months. After haploidentical transplantation, patients without complications, mainly a GVHD ≥ grade 2, will receive mDLI. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bone Marrow Transplant Infection, Bone Marrow Transplant Complications, Graft Vs Host Disease
- What is being tested?
- modified donor lymphocytes infusion (mDLI)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteItaly
- Study dates
- 13 Nov 2018to 8 Jan 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written, signed informed consent;
- Adult patients aged ≥18 years;
- Patients who underwent haploidentical transplantation with PT-Cy for haematological diseases since no more than 56 days;
- Patient who received myeloablative conditioning regimen, reduced intensity conditioning regimens, or non-myeloablative conditioning regimens;
- Availability of haploidentical donor (defined as those with ≥ 2 differences within one HLA haplotype) who agree to donate peripheral blood cells by leukapheresis and able to donate the day before the day planned for infusion (or up to - 7 days);
- GVHD/HVG prophylaxis consists in Cyclophosphamide: 50 mg/kg/day, day +3 and +4, Cyclosporine A: 3 mg/kg/day from day +5 to day +100, with tapering in 2 months Mycophenolate mofetil: 45 mg/kg/day, from day +5 to day +35.
Who cannot join
- Presence of grade 2-4 acute GVHD;
- Uncontrolled bacterial, viral or fungal infection;
- Aplasia defined as ANC less than 500/L;
- Evidence of disease progression after transplantation;
- Current participation in another clinical study.
Trial locations and contacts
1 site in 1 country.
About this study
Interventional non-randomized trial. The duration of study will be 47 months.
After haploidentical transplantation, patients without complications, mainly a GVHD ≥ grade 2, will receive mDLI. mDLI consists of donor lymphocytes infusion, harvested by apheresis the day before the day planned for infusion (or up to -7 days) as outpatient basis in the Day Hospital using a cell separator.
Read more
The mDLIs preparation will be performed using a CliniMACS® (Miltenyi). A CD45RA-depletion Product LineTM from Miltenyi, including disposable reagents and devices, will be used.
The planned number of mDLI is 3.
- Day +50 (+/- 7 days) from allogenic transplant, 1st mDLI 5x105CD3+/kg of recipient.
- 4-6 weeks after 1st DLI, 2nd mDLI 1x106CD3+/kg of recipient.
- 4-6 weeks after 2nd DLI, 3rd mDLI 5x106CD3+/kg of recipient. Day +50 was chosen as the starting time-point because at that time over two thirds of all acute GvHD episodes have already occurred in the absence of DLI (internal data, median +49 after bone marrow, +27 after peripheral stem cells); acute GvHD will thus be less likely a confounding factor. The choice of a maximum number of 3 mDLIs is based on the relatively narrow time interval where outcome improvement is expected, that is mainly in the first 6 months after haplo-HSCT. The planned doses are those mainly used in conventional DLIs during haplo-HSCT setting.
Stopping infusion rules:
If GvHD ≥ Grade 2 or relapse occurs, mDLIs will not be administered at any time and patient will be permanently discontinued from treatment.
If any severe adverse event (SAE) occurs after the first mDLI, the administration of mDLI will be interrupted for a maximum of 6 weeks until event resolution. If the SAE does not resolve after 6 weeks from last mDLI infusion, patient will be permanently discontinued. At any time, the experimental treatment may be stopped according to clinical judgement or patient's willing.
- Conditions
- Bone Marrow Transplant Infection, Bone Marrow Transplant Complications, Graft Vs Host Disease, Infection, Hematological Malignancy
- Being tested
- modified donor lymphocytes infusion (mDLI)
- Keywords
- DLI, CD45+, donor lymphocytes infusion, mDLI, haploidentical transplantation, hematological malignancies
- Medical subject headings
- Graft vs Host Disease, Infections, Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
modified donor lymphocytes infusion (mDLI)Biological
The planned number of mDLI is 3.
- Day +50 (+/- 7 days) from allogenic transplant, 1st mDLI 5x105CD3+/kg of recipient.
- 4-6 weeks after 1st DLI, 2nd mDLI 1x106CD3+/kg of recipient.
- 4-6 weeks after 2nd DLI, 3rd mDLI 5x106CD3+/kg of recipient.
| Study group | Role | What they receive |
|---|---|---|
| mDLI infusion | Experimental | The planned number of mDLI is 3.
1. Day +50 (+/- 7 days) from allogenic transplant, 1st mDLI 5x105CD3+/kg of recipient.
2. 4-6 weeks after 1st DLI, 2nd mDLI 1x106CD3+/kg of recipient.
3. 4-6 weeks after 2nd DLI, 3rd mDLI 5x106CD3+/kg of recipient. Receives: Biological: modified donor lymphocytes infusion (mDLI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
to evaluate the efficacy of CD45RA-depleted haplo-DLIs (mDLIs) in the setting of patients receiving haplo-HSCT and PT-Cy, in terms of incidence of viral infections in the post-transplant period
The primary endpoint is the rate of viral infections at day +100 after haplo-BMT.
Measured: 100 days
to evaluate the impact of the modified DLIs on the occurrence of GvHD
acute and chronic GvHD incidence
Measured: 1 year
to evaluate the impact of the modified DLIs on relapse (graft-versus-tumor effect)
relapse rate
Measured: 1 year
to evaluate the impact of the modified DLIs on other types of infections;
100-day cumulative incidence of other type of infections
Measured: 100 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2020
- Study start13 Nov 2018
- Primary completion8 Jan 2020
- Study completion8 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bone Marrow Transplant InfectionStudies of the same condition, open and under way.
- More trials run by Istituto Clinico HumanitasThe 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 N/A
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Istituto Clinico Humanitas
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04687982
- Sponsor's protocol ID
- ONC-2016-002
- Status last verified
- Dec 2020
- First submitted
- 10 Dec 2020
- Last updated
- 29 Dec 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
van Beek JJP, Puccio S, Di Vito C, De Paoli F, Zaghi E, Calvi M, Scarpa A, Peano C, Basso G, Cibella J, De Philippis C, Sarina B, Timofeeva I, Capizzuto R, Mannina D, Mineri R, Mariotti J, Crocchiolo R, Santoro A, Castagna L, Bramanti S, Mavilio D, Lugli E. Selected memory T cells infused post-haploidentical hematopoietic stem cell transplantation persist and hyperexpand. Blood Adv. 2023 Jul 25;7(14):3458-3468. doi: 10.1182/bloodadvances.2022007735.
PubMed 36469095
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Feasibility and Efficacy of Modified Donor Lymphocytes Infusion (CD45RA Negative Selected) After Haploidentical Transplantation With Post-transplantation Cyclophosphamide in Patients With Hematological Malignancies (ONC-2016-002).
- ClinicalTrials.gov ID
- NCT04687982
- Acronym / sponsor ID
- ONC-2016-002
- Conditions
- Bone Marrow Transplant Infection, Bone Marrow Transplant Complications, Graft Vs Host Disease, Infection, Hematological Malignancy
- Keywords
- DLI, CD45+, donor lymphocytes infusion, mDLI, haploidentical transplantation, hematological malignancies
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Istituto Clinico HumanitasUniversity, hospital or other
- Study start
- 13 Nov 2018 (actual)
- Primary completion
- 8 Jan 2020 (actual)
- Study completion
- 8 Jan 2020 (actual)
- First posted
- 29 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Interventional non-randomized trial. The duration of study will be 47 months.
After haploidentical transplantation, patients without complications, mainly a GVHD ≥ grade 2, will receive mDLI. mDLI consists of donor lymphocytes infusion, harvested by apheresis the day before the day planned for infusion (or up to -7 days) as outpatient basis in the Day Hospital using a cell separator.
The mDLIs preparation will be performed using a CliniMACS® (Miltenyi). A CD45RA-depletion Product LineTM from Miltenyi, including disposable reagents and devices, will be used.
The planned number of mDLI is 3.
- Day +50 (+/- 7 days) from allogenic transplant, 1st mDLI 5x105CD3+/kg of recipient.
- 4-6 weeks after 1st DLI, 2nd mDLI 1x106CD3+/kg of recipient.
- 4-6 weeks after 2nd DLI, 3rd mDLI 5x106CD3+/kg of recipient. Day +50 was chosen as the starting time-point because at that time over two thirds of all acute GvHD episodes have already occurred in the absence of DLI (internal data, median +49 after bone marrow, +27 after peripheral stem cells); acute GvHD will thus be less likely a confounding factor. The choice of a maximum number of 3 mDLIs is based on the relatively narrow time interval where outcome improvement is expected, that is mainly in the first 6 months after haplo-HSCT. The planned doses are those mainly used in conventional DLIs during haplo-HSCT setting.
Stopping infusion rules:
If GvHD ≥ Grade 2 or relapse occurs, mDLIs will not be administered at any time and patient will be permanently discontinued from treatment.
If any severe adverse event (SAE) occurs after the first mDLI, the administration of mDLI will be interrupted for a maximum of 6 weeks until event resolution. If the SAE does not resolve after 6 weeks from last mDLI infusion, patient will be permanently discontinued. At any time, the experimental treatment may be stopped according to clinical judgement or patient's willing.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| mDLI infusion | Experimental | Biological: modified donor lymphocytes infusion (mDLI)The planned number of mDLI is 3. 1. Day +50 (+/- 7 days) from allogenic transplant, 1st mDLI 5x105CD3+/kg of recipient. 2. 4-6 weeks after 1st DLI, 2nd mDLI 1x106CD3+/kg of recipient. 3. 4-6 weeks after 2nd DLI, 3rd mDLI 5x106CD3+/kg of recipient. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Written, signed informed consent;
- Adult patients aged ≥18 years;
- Patients who underwent haploidentical transplantation with PT-Cy for haematological diseases since no more than 56 days;
- Patient who received myeloablative conditioning regimen, reduced intensity conditioning regimens, or non-myeloablative conditioning regimens;
- Availability of haploidentical donor (defined as those with ≥ 2 differences within one HLA haplotype) who agree to donate peripheral blood cells by leukapheresis and able to donate the day before the day planned for infusion (or up to - 7 days);
Key exclusion criteria (5 listed)
- Presence of grade 2-4 acute GVHD;
- Uncontrolled bacterial, viral or fungal infection;
- Aplasia defined as ANC less than 500/L;
- Evidence of disease progression after transplantation;
- Current participation in another clinical study.
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 |
|---|---|---|
| modified donor lymphocytes infusion (mDLI)The planned number of mDLI is 3. 1. Day +50 (+/- 7 days) from allogenic transplant, 1st mDLI 5x105CD3+/kg of recipient. 2. 4-6 weeks after 1st DLI, 2nd mDLI 1x106CD3+/kg of recipient. 3. 4-6 weeks after 2nd DLI, 3rd mDLI 5x106CD3+/kg of recipient. | Biological | mDLI infusion |
Primary outcome
to evaluate the efficacy of CD45RA-depleted haplo-DLIs (mDLIs) in the setting of patients receiving haplo-HSCT and PT-Cy, in terms of incidence of viral infections in the post-transplant period
Time frame: 100 days
The primary endpoint is the rate of viral infections at day +100 after haplo-BMT.
to evaluate the impact of the modified DLIs on the occurrence of GvHD
Time frame: 1 year
acute and chronic GvHD incidence
to evaluate the impact of the modified DLIs on relapse (graft-versus-tumor effect)
Time frame: 1 year
relapse rate
to evaluate the impact of the modified DLIs on other types of infections;
Time frame: 100 days
100-day cumulative incidence of other type of infections
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2020.
- Derived from this study: PubMed 36469095van Beek JJP, Puccio S, Di Vito C, De Paoli F, Zaghi E, Calvi M, Scarpa A, Peano C, Basso G, Cibella J, De Philippis C, Sarina B, Timofeeva I, Capizzuto R, Mannina D, Mineri R, Mariotti J, Crocchiolo R, Santoro A, Castagna L, Bramanti S, Mavilio D, Lugli E. Selected memory T cells infused post-haploidentical hematopoietic stem cell transplantation persist and hyperexpand. Blood Adv. 2023 Jul 25;7(14):3458-3468. doi: 10.1182/bloodadvances.2022007735.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing modified donor lymphocytes infusion (mDLI) in people with Bone Marrow Transplant Infection and Bone Marrow Transplant Complications, run by Istituto Clinico Humanitas at 1 site in Italy.
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 6 inclusion and 5 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: finished, as of the sponsor's last update on 29 Dec 2020. 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 Italy. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
to evaluate the efficacy of CD45RA-depleted haplo-DLIs (mDLIs) in the setting of patients receiving haplo-HSCT and PT-Cy, in terms of incidence of viral infections in the post-transplant period (time frame: 100 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04687982, which also lists 1 linked publication.
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 29 Dec 2020.