Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT01685606
Other study ID # BrUOG 273
Secondary ID
Status Terminated
Phase Phase 2
First received
Last updated
Start date March 2013
Est. completion date June 2015

Study information

Verified date February 2022
Source Brown University
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The study of whether an infusion of blood cells called lymphocytes from a donor can stimulate the immune system to fight your leukemia/lymphoma.


Description:

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.


Recruitment information / eligibility

Status Terminated
Enrollment 6
Est. completion date June 2015
Est. primary completion date June 2015
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Histologic confirmation of hematological malignancy consisting of the following leukemias/lymphomas: - Mantle cell lymphoma with Ki-67>30% - Diffuse Large Cell Lymphoma - Burkitts Lymphoma - Systemic T Cell Lymphomas - Acute Myeloid Leukemia - Acute Lymphoblastic Leukemia - Recurrence or progression of hematological malignancy after at least 1 prior standard treatment with progression within 6 months from last treatment. - No curative treatment option is available. -> 4-weeks since prior chemotherapy or radiation to cellular therapy infusion. (Hydroxyurea may be utilized up to 48 hours prior to initiation of treatment on this protocol). - Age equal to or greater than 18 years. - Patients with a history of invasive second malignancy unless disease free for > 5 years. - Patients must have an expected life expectancy of at least 2 months at the time of initiation of treatment. - No active systemic infection. - Patients who have relapsed after standard autologous stem cell infusion are eligible as long as they meet all inclusion criteria and no exclusion criteria. These patients must be out more than 6 months from cell infusion to be eligible for enrollment. - DLCO > 40% with no symptomatic pulmonary disease. - LVEF > 40% by MUGA or echocardiogram. - Creatinine < 2.0 mg/dl. Total bilirubin less than 1.5x the upper limit of normal (ULN), AST < 3x ULN. - Non-pregnant and willing to use appropriate birth control during the duration of the study period. Exclusion Criteria: - Evidence of HIV infection. - Any uncontrolled severe, concurrent illness which in the opinion of the treating physician would make this protocol treatment unreasonably hazardous for the patient. - Oxygen dependent obstructive pulmonary disease. - Failure to demonstrate adequate compliance with medical therapy and follow-up. - Significant medical or psychiatric illness that would impair the ability to participate in protocol therapy. - For women of reproductive potential, refusal to use effective form of contraception. - Previous allogeneic stem cell transplant - Patients who have had previous purine analog (fludarabine, pentostatin, 2-CDA) -Patients with chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), multiple myeloma, and indolent lymphoma (follicular lymphoma, marginal zone lymphoma) - Patients with HLA antibodies to donor HLA type.

Study Design


Related Conditions & MeSH terms


Intervention

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.

Locations

Country Name City State
United States Rhode Island Hospital Providence Rhode Island
United States The Miriam Hospital Providence Rhode Island

Sponsors (1)

Lead Sponsor Collaborator
Brown University

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Overall Response Rate of Cellular Immune Therapy With HLA Haploidentical Peripheral Blood Pheresed Cells in Patients With Relapsed/Refractory Hematological Malignancies. Criteria for AML and ALL (adapted from Cheson et al.20)
Complete remission (CR) is defined as the presence of all of the following
Peripheral blood
o No leukemic blasts present.
No extramedullary findings of leukemia or disappearance of such (i.e. CNS or soft tissue involvement)
Bone marrow
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.
8 weeks after infusion then 6 months after and every 4 months for approximately 2 years
Secondary To Evaluate the Rate of Dose Limiting Toxicities of HLA Haploidentical Peripheral Blood Pheresed Cellular Infusions. 30 days and 16 weeks after infusion
See also
  Status Clinical Trial Phase
Enrolling by invitation NCT01804686 - A Long-term Extension Study of PCI-32765 (Ibrutinib) Phase 3
Recruiting NCT05976763 - Testing Continuous Versus Intermittent Treatment With the Study Drug Zanubrutinib for Older Patients With Previously Untreated Mantle Cell Lymphoma Phase 3
Recruiting NCT03676504 - Treatment of Patients With Relapsed or Refractory CD19+ Lymphoid Disease With T Cells Expressing a Third-generation CAR Phase 1/Phase 2
Recruiting NCT05365659 - IKS03 in Patients With Advanced B Cell Non-Hodgkin Lymphomas Phase 1
Recruiting NCT05471843 - Study of BGB-11417 Monotherapy in Participants With Relapsed or Refractory Mantle Cell Lymphoma Phase 1/Phase 2
Recruiting NCT05076097 - A Study of OLR in First-line Treatment of Mantle Cell Lymphoma Phase 2
Active, not recruiting NCT04082936 - A Study of Imvotamab Monotherapy and in Combination in Subjects With Relapsed/Refractory Non-Hodgkin Lymphoma Phase 1/Phase 2
Active, not recruiting NCT03891355 - Carfilzomib + Lenalidomide and Dexamethasone for BTK Inhibitors Relapsed-refractory or Intolerant MCL Phase 2
Recruiting NCT04883437 - Acalabrutinib and Obinutuzumab for the Treatment of Previously Untreated Follicular Lymphoma or Other Indolent Non-Hodgkin Lymphomas Phase 2
Terminated NCT03585725 - A Pilot Investigator-Initiated Study of Ribavirin in Indolent Follicular Lymphoma and Mantle Cell Lymphoma Early Phase 1
Recruiting NCT02892695 - PCAR-119 Bridge Immunotherapy Prior to Stem Cell Transplant in Treating Patients With CD19 Positive Leukemia and Lymphoma Phase 1/Phase 2
Terminated NCT02877082 - Tacrolimus, Bortezomib, & Thymoglobulin in Preventing Low Toxicity GVHD in Donor Blood Stem Cell Transplant Patients Phase 2
Completed NCT01665768 - Maintenance Rituximab With mTor Inhibition After High-dose Consolidative Therapy in Lymphoma Phase 2
Completed NCT01437709 - Ofatumumab With or Without Bendamustine for Patients With Mantle Cell Lymphoma Ineligible for Autologous Stem Cell Transplant Phase 2
Completed NCT00963534 - Lenalidomide, Bendamustine and Rituximab as First-line Therapy for Patients Over 65 Years With Mantle Cell Lymphoma. Phase 1/Phase 2
Completed NCT00921414 - Mantel Cell Lymphoma Efficacy of Rituximab Maintenance Phase 3
Withdrawn NCT00541424 - Combined CT Colonography and PET Imaging in Mantle Cell Lymphoma N/A
Completed NCT01456351 - Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab Phase 3
Completed NCT01851551 - Phase 1/2 Study of VSLI Plus Rituximab in Patients With Relapsed and/or Refractory NHL Phase 1/Phase 2
Completed NCT03295240 - The Study of Bendamustine, Rituximab, Ibrutinib, and Venetoclax in Relapsed, Refractory Mantle Cell Lymphoma Early Phase 1