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
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|ClinicalTrials.gov Identifier: NCT02342613|
Recruitment Status : Active, not recruiting
First Posted : January 21, 2015
Last Update Posted : May 3, 2019
|Condition or disease||Intervention/treatment||Phase|
|Hematologic Malignancies Graft-Versus-Host Disease||Biological: Activated PTCy-MILs||Phase 1|
- 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.
- 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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||27 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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.|
|Actual Study Start Date :||May 28, 2015|
|Estimated Primary Completion Date :||February 2020|
|Estimated Study Completion Date :||February 2020|
Experimental: MILs treatment
Patients treated with the activated PTCy-MILs
Biological: Activated PTCy-MILs
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.
- 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.
- Optimal safe dose for PTCy-MILs [ Time Frame: 90 days ]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
- Immunologic characterization of the PTCy-MIL product before and after expansion [ Time Frame: up to 3 years ]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.
- Number of participants who experience chronic GVHD [ Time Frame: up to 2 years post-transplant ]Chronic GVHD is defined by National Institutes of Health (NIH) criteria.
- Clinical Response [ Time Frame: up to 3 years ]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
- Progression-Free Survival [ Time Frame: up to 3 years ]Time from day of PTCy-MILs infustion to progression/relapse of disease or death from any cause, whichever occurs first
- Overall Survival [ Time Frame: up to 3 years ]Time alive from the day of PTCy-MILs infusion to death from any cause
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02342613
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21231|
|Principal Investigator:||Leo Luznik, MD||Sidney Kimmel Cancer Center at Johns Hopkins|