Study of Infusion of Blood Cells (Lymphocytes) to Stimulate the Immune System to Fight Leukemia/Lymphoma (273)
|ClinicalTrials.gov Identifier: NCT01685606|
Recruitment Status : Terminated (Lack of accrual and low efficacy)
First Posted : September 14, 2012
Results First Posted : June 26, 2015
Last Update Posted : August 11, 2015
|Condition or disease||Intervention/treatment||Phase|
|Mantle Cell Lymphoma Diffuse Large Cell Lymphoma Burkitts Lymphoma T Cell Lymphomas Acute Myeloid Leukemia/Acute Lymphoblastic Leukemia||Biological: cellular immunotherapy||Phase 2|
There have been important advances in the modulation of the immune system for the treatment of hematologic malignancies and solid tumors.
This protocol will build upon these previous observations as follows:
- Haploidentical peripheral blood pheresed cells will be used at 1-2x108 CD3 cells/kg.
Total body radiation will not be utilized.
- This modification may more effectively activate the recipient's immune system to attack their hematological malignancy by not damaging the recipient's immune cells prior to cellular infusion. Safety should be improved since the risk of graft versus host disease should be greatly reduced as the host's immune system will not be conditioned.
Granulocyte-colony stimulating factor (G-CSF) priming will not be used.
- In our first clinical trial, G-CSF priming was not used for matched transplants. Our second trial did employ G-CSF priming in the haplo-identical setting. Previous data has cited a role for G-CSF in stimulation of invariant Natural Killer(NK) cells with enhanced GVL effects11. However, our most recent laboratory data with unprimed PBMC has shown effective cell kill activity without the addition of G-CSF. As G-CSF would be administered to healthy volunteers, the unclear benefit of the addition of this cytokine is offset by the potential side effects such as headache, fever, and bone pain. G-CSF mobilization serves to shift the response from a TH1 to TH2 through the increased production of T regulatory cells. The end result would be a decrease in immune stimulation. Since the goal of this study is to NOT have engraftment, the manipulation of the donor cells to dampen the host versus tumor stimulation is not needed nor desired. Furthermore, since this protocol is not a stem cell transplant, stem cells do not need to be mobilized with G-CSF.
It is important to note that the proposed study is not a stem cell transplant study. In the situation of stem cell transplants, the goal of the procedure is to have engraftment, or sustainable donor chimerism in the marrow to provide hematopoietic reconstitution as well as immunologic reconstitution. In this study, we are evaluating the use of donor lymphocytes (not stem cells) to stimulate an immune response of the recipients' immune system.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||BrUOG 273:Cellular Immunotherapy For Refractory Hematological Malignancies:A Brown University Oncology Research Group Study|
|Study Start Date :||March 2013|
|Actual Primary Completion Date :||June 2015|
|Actual Study Completion Date :||June 2015|
Experimental: cellular immunotherapy
A minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg from a haploidentical donor will be infused, irrespective of the number of CD34+ cells.
Biological: cellular immunotherapy
A minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg from a haploidentical donor irrespective of the number of CD34+ cells will be infused.
- Overall Response Rate of Cellular Immune Therapy With HLA Haploidentical Peripheral Blood Pheresed Cells in Patients With Relapsed/Refractory Hematological Malignancies. [ Time Frame: 8 weeks after infusion then 6 months after and every 4 months for approximately 2 years ]
Criteria for AML and ALL (adapted from Cheson et al.20)
Complete remission (CR) is defined as the presence of all of the following
o No leukemic blasts present.
- No extramedullary findings of leukemia or disappearance of such (i.e. CNS or soft tissue involvement)
- Cellularity >20% with baseline maturation.
- No Auer rods
- Less than 5% blast cells.
- Complete blood counts and bone marrow normalization criteria must be met within one week of each other. Hematopoeitic recovery is an ANC > 1.0 x 109/L and platelet count > 100x109/L. No specific hemoglobin or hematocrit level is specified but the patient must be transfusion free.
Complete remission with incomplete recovery (CRi) is defined as the following:
- Meets criteria for CR except
- ANC < 1.0 x 109/L or platelet count < 100x109/L
Partial remission (PR).
• Must meet all criteria of a CR except that the bone marrow may contain 5-20% blasts.
- To Evaluate the Rate of Dose Limiting Toxicities of HLA Haploidentical Peripheral Blood Pheresed Cellular Infusions. [ Time Frame: 30 days and 16 weeks after infusion ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01685606
|United States, Rhode Island|
|Rhode Island Hospital|
|Providence, Rhode Island, United States, 02903|
|The Miriam Hospital|
|Providence, Rhode Island, United States, 02903|
|Principal Investigator:||Peter Quesenberry, MD||Brown University|