Hematologic MalignanciesPhase 1NCT02342613
Adoptive Immunotherapy With Activated Marrow Infiltrating Lymphocytes and Cyclophosphamide Graft-Versus-Host Disease Prophylaxis in Patients With Relapse of Hematologic Malignancies After Allogeneic Hematopoietic Cell Transplantation
A Phase 1 study testing Activated PTCy-MILs in people with Hematologic Malignancies and Graft-Versus-Host Disease, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial summary
This Phase 1 clinical study is designed to examine the safety and feasibility of using anti-CD3/CD28 activated marrow infiltrating lymphocytes (MILs) as treatment of relapse after allogeneic hematopoietic cell transplantation (alloHCT) for patients with hematologic malignancies with bone marrow involvement of their… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematologic Malignancies, Graft-Versus-Host Disease
- What is being tested?
- Activated PTCy-MILs
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 28 May 2015to 31 Mar 2024
- Phase
- Phase 1
- 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
- Age ≥18 years old
- Bone marrow relapse of a hematologic malignancy ≥6 months after alloHCT using PTCy
- Donor CD3+ chimerism ≥ 30% measured in peripheral blood or bone marrow
- ECOG performance status ≤ 2 or Karnofsky performance scale ≥ 70%.
- Off all immunosuppressive drugs for 2 weeks prior to the PTCy-MILs collection.
- Expectation of ability to safely undergo salvage treatment appropriate for the patient's malignant disease type as determined by the treating hematologist/ oncologist.
Who cannot join
- Most recent alloHCT not utilizing PTCy.
- Active GVHD requiring treatment.
- Immunosuppression use within 28 days of PTCy-MIL infusion if prior grade II-IV acute GVHD.
- Creatinine ≥ 2.5, total bilirubin > 3 times the upper limit of normal (ULN), or AST/ALT > 3 times the ULN.
- HIV-1/2 or HTLV-1/2 positivity.
- Life expectancy ≤ 90 days even with aggressive treatment, as determined by the treating hematologist/oncologist, which would preclude assessment of toxicity of PTCy-MILs
Trial locations and contacts
1 site in 1 country.
United States1 site
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231
About this study
Official title: Adoptive Immunotherapy Utilizing Activated Marrow Infiltrating Lymphocytes Derived From Patients With Bone Marrow Relapse of Hematologic Malignancies After Allogeneic Hematopoietic Cell Transplantation Using Post-Transplantation Cyclophosphamide Graft-Versus-Host Disease Prophylaxis.
This Phase 1 clinical study is designed to examine the safety and feasibility of using anti-CD3/CD28 activated marrow infiltrating lymphocytes (MILs) as treatment of relapse after allogeneic hematopoietic cell transplantation (alloHCT) for patients with hematologic malignancies with bone marrow involvement of their relapsed disease. These MILs will be derived from the bone marrow of the relapsed patient who had previously received post-transplantation cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis (PTCy-MILs). A bone marrow aspiration will be performed on the patient to collect ~200ml of marrow for ex vivo expansion. During this expansion process, T cells will be activated and expanded by co-stimulation with anti-CD3/anti-CD28 monoclonal antibodies covalently attached to super-paramagnetic microbeads. Patients will be treated with salvage therapy while this ex vivo expansion is ongoing. After the simultaneous salvage therapy and ex vivo expansion, the activated PTCy-MILs will be reinfused. Patients will be monitored with the primary objective being the feasibility of expanding to targeted dose levels activated PTCy-MILs that do not cause grade III-IV acute GVHD within the first 90 days after PTCy-MIL infusion.
Read the detailed description
Primary Objectives:
- Feasibility of generating activated PTCy-MILs in patients with relapsed disease involving the bone marrow.
- Toxicity of PTCy-MILs, specifically the rate of grade III-IV acute GVHD within the first 90 days after PTCy-MIL infusion.
Secondary Objectives
- Determination of an optimal safe dose for PTCy-MILs.
- Immunologic characterization of the PTCy-MIL product before and after expansion.
- Immune reconstitution after treatment with PTCy-MILs.
- Incidence and severity of chronic GVHD.
- Clinical responses (complete remissions, partial remissions, stable disease) as measured by criteria specific for the particular disease type.
- Progression-free and overall survival.
- Being tested
- Activated PTCy-MILs
- 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.
Activated PTCy-MILsBiological
The activated PTCy-MILs will be infused through standard blood tubing containing a 170-260 micron filter without an additional leukoreduction filter into a central IV site. Each of the bags will be infused at a rate of approximately 10 ml per minute. The IV line will be flushed with normal saline immediately after completion of PTCy-MILs infusion to ensure that all product has been infused into the patient.
| Study group | Role | What they receive |
|---|---|---|
| MILs treatment | Experimental | Patients treated with the activated PTCy-MILs Receives: Biological: Activated PTCy-MILs |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility of generating activated marrow infiltrating lymphocytes (MILs) from participants previously treated with post-transplantation cyclophosphamide (PTCy) (PTCy-MILs) who have relapsed disease involving the bone marrow
Feasibility is measured as the number of participants who achieve: 1) The successful obtaining of PTCy-MILs; 2) The expansion of PTCy-MILs to at least 70% of the assigned dose level; 3) Successful infusion of PTCy-MILs; 4) The absence of grade III-IV acute graft-versus-host-disease (GVHD) for 90 days after PTCy-MILs infusion. Acute GVHD is defined by the Modified Keystone Criteria.
Measured: 90 days
Secondary outcomes (6)
Optimal safe dose for PTCy-MILs
Optimal safe dose is defined as the maximal MILs cell dose that can be expanded in at least 70% of patients at which upon administration does not exacerbate grade III/IV GVHD
Measured: 90 days
Immunologic characterization of the PTCy-MIL product before and after expansion
Amount of MILs with expression of CD3, CD4, Cd8, CXCR4, CD45RO, CD62L, CD107a, FasL, markers of exhaustion and T-cell inactivation as identified by multi-color flow cytometry and functional studies of alloMILs and T-cell response.
Measured: up to 3 years
Number of participants who experience chronic GVHD
Chronic GVHD is defined by National Institutes of Health (NIH) criteria.
Measured: up to 2 years post-transplant
Clinical Response
Number of participants with complete remission (CR), partial remission (PR) and stable disease (SD) as assessed by bone marrow examination, CBC with differential, serum chemistries, cytogenetics and disease-specific molecular studies
Measured: up to 3 years
Progression-Free Survival
Time from day of PTCy-MILs infustion to progression/relapse of disease or death from any cause, whichever occurs first
Measured: up to 3 years
Overall Survival
Time alive from the day of PTCy-MILs infusion to death from any cause
Measured: up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jan 2015 (estimated)
- Study start28 May 2015
- Primary completion29 Nov 2023
- Study completion31 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematologic MalignanciesStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Sponsor
- Investigators
- Philip Imus, MD, Principal investigator, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02342613
- Sponsor's protocol ID
- J1484
- Other IDs
- IRB00039074, P01CA153962
- Status last verified
- Jan 2025
- First submitted
- 15 Jan 2015
- Last updated
- 7 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adoptive Immunotherapy Utilizing Activated Marrow Infiltrating Lymphocytes Derived From Patients With Bone Marrow Relapse of Hematologic Malignancies After Allogeneic Hematopoietic Cell Transplantation Using Post-Transplantation Cyclophosphamide Graft-Versus-Host Disease Prophylaxis.
- ClinicalTrials.gov ID
- NCT02342613
- Acronym / sponsor ID
- J1484
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- 28 May 2015 (actual)
- Primary completion
- 29 Nov 2023 (actual)
- Study completion
- 31 Mar 2024 (actual)
- First posted
- 21 Jan 2015 (estimated)
- 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.
This Phase 1 clinical study is designed to examine the safety and feasibility of using anti-CD3/CD28 activated marrow infiltrating lymphocytes (MILs) as treatment of relapse after allogeneic hematopoietic cell transplantation (alloHCT) for patients with hematologic malignancies with bone marrow involvement of their relapsed disease. These MILs will be derived from the bone marrow of the relapsed patient who had previously received post-transplantation cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis (PTCy-MILs). A bone marrow aspiration will be performed on the patient to collect ~200ml of marrow for ex vivo expansion. During this expansion process, T cells will be activated and expanded by co-stimulation with anti-CD3/anti-CD28 monoclonal antibodies covalently attached to super-paramagnetic microbeads. Patients will be treated with salvage therapy while this ex vivo expansion is ongoing. After the simultaneous salvage therapy and ex vivo expansion, the activated PTCy-MILs will be reinfused. Patients will be monitored with the primary objective being the feasibility of expanding to targeted dose levels activated PTCy-MILs that do not cause grade III-IV acute GVHD within the first 90 days after PTCy-MIL infusion.
Detailed description
Primary Objectives:
- Feasibility of generating activated PTCy-MILs in patients with relapsed disease involving the bone marrow.
- Toxicity of PTCy-MILs, specifically the rate of grade III-IV acute GVHD within the first 90 days after PTCy-MIL infusion.
Secondary Objectives
- Determination of an optimal safe dose for PTCy-MILs.
- Immunologic characterization of the PTCy-MIL product before and after expansion.
- Immune reconstitution after treatment with PTCy-MILs.
- Incidence and severity of chronic GVHD.
- Clinical responses (complete remissions, partial remissions, stable disease) as measured by criteria specific for the particular disease type.
- Progression-free and overall survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MILs treatment | Experimental | Biological: Activated PTCy-MILsPatients treated with the activated PTCy-MILs |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age ≥18 years old
- Bone marrow relapse of a hematologic malignancy ≥6 months after alloHCT using PTCy
- Donor CD3+ chimerism ≥ 30% measured in peripheral blood or bone marrow
- ECOG performance status ≤ 2 or Karnofsky performance scale ≥ 70%.
- Off all immunosuppressive drugs for 2 weeks prior to the PTCy-MILs collection.
Key exclusion criteria (6 listed)
- Most recent alloHCT not utilizing PTCy.
- Active GVHD requiring treatment.
- Immunosuppression use within 28 days of PTCy-MIL infusion if prior grade II-IV acute GVHD.
- Creatinine ≥ 2.5, total bilirubin > 3 times the upper limit of normal (ULN), or AST/ALT > 3 times the ULN.
- HIV-1/2 or HTLV-1/2 positivity.
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 |
|---|---|---|
| Activated PTCy-MILsThe activated PTCy-MILs will be infused through standard blood tubing containing a 170-260 micron filter without an additional leukoreduction filter into a central IV site. Each of the bags will be infused at a rate of approximately 10 ml per minute. The IV line will be flushed with normal saline immediately after completion of PTCy-MILs infusion to ensure that all product has been infused into the patient. | Biological | MILs treatment |
Primary outcome
Feasibility of generating activated marrow infiltrating lymphocytes (MILs) from participants previously treated with post-transplantation cyclophosphamide (PTCy) (PTCy-MILs) who have relapsed disease involving the bone marrow
Time frame: 90 days
Feasibility is measured as the number of participants who achieve: 1) The successful obtaining of PTCy-MILs; 2) The expansion of PTCy-MILs to at least 70% of the assigned dose level; 3) Successful infusion of PTCy-MILs; 4) The absence of grade III-IV acute graft-versus-host-disease (GVHD) for 90 days after PTCy-MILs infusion. Acute GVHD is defined by the Modified Keystone Criteria.
6 secondary outcomes
Optimal safe dose for PTCy-MILs
Time frame: 90 days
Immunologic characterization of the PTCy-MIL product before and after expansion
Time frame: up to 3 years
Number of participants who experience chronic GVHD
Time frame: up to 2 years post-transplant
Clinical Response
Time frame: up to 3 years
Progression-Free Survival
Time frame: up to 3 years
Overall Survival
Time frame: up to 3 years
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 7 Jan 2025.
- 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.
Philip Imus, MD principal investigator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Activated PTCy-MILs in people with Hematologic Malignancies and Graft-Versus-Host Disease, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins 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 6 inclusion and 6 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 7 Jan 2025. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Feasibility of generating activated marrow infiltrating lymphocytes (MILs) from participants previously treated with post-transplantation cyclophosphamide (PTCy) (PTCy-MILs) who have relapsed disease involving the bone marrow (time frame: 90 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 7 Jan 2025.