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| ID | Type | Description | Link |
|---|---|---|---|
| IRB00039074 | Other Identifier | JHM IRB | |
| P01CA153962 | Other Grant/Funding Number | NIH |
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
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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.
Primary Objectives:
Secondary Objectives
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MILs treatment | Experimental | Patients treated with the activated PTCy-MILs |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Activated PTCy-MILs | Biological | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 90 days |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 90 days |
| Immunologic characterization of the PTCy-MIL product before and after expansion |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Philip Imus, MD | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore | Maryland | 21231 | United States |
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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. |
| up to 3 years |
| Number of participants who experience chronic GVHD | Chronic GVHD is defined by National Institutes of Health (NIH) criteria. | 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 | 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 | up to 3 years |
| Overall Survival | Time alive from the day of PTCy-MILs infusion to death from any cause | up to 3 years |
| 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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