Administration of TAA-Specific CTLs; Hodgkin or Non-Hodgkin Lymphoma; TACTAL (TACTAL)
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|ClinicalTrials.gov Identifier: NCT01333046|
Recruitment Status : Active, not recruiting
First Posted : April 11, 2011
Last Update Posted : April 11, 2022
Patients have a type of lymph gland disease called Hodgkin or non-Hodgkin lymphoma which has come back, or may come back, or has not gone away after treatment, including the standard treatment known for these diseases. This a research study using special immune system cells called tumor associated antigen (TAA)-specific cytotoxic T lymphocytes, a new experimental therapy.
This sort of therapy has been used previously to treat Hodgkin or non-Hodgkin lymphomas that show proof of infection with Epstein-Barr virus (EBV), the virus that causes infectious mononucleosis ("mono" or the "kissing disease"). EBV is found in cancer cells of up to half of all patients with Hodgkin's and non-Hodgkin lymphoma. This suggests that it may play a role in causing lymphoma. The cancer cells infected by EBV are able to hide from the body's immune system and escape being killed. Investigators tested whether special white blood cells, called T cells, that were trained to kill EBV-infected cells could affect these tumors, and in many patients it was found that giving these trained T cells caused a complete or partial response.
However, many patients do not have EBV in their lymphoma cells; therefore investigators now want to test whether it is possible to direct these special T cells against other types of proteins on the tumor cell surface with similar promising results. The proteins that will be targeted in this study are called tumor associated antigens (TAAs) - these are cell proteins that are specific to the cancer cell, so they either do not show or show up in low quantities on normal human cells.
In this study, we will target five TAAs which commonly show on lymphoma, called: NY-ESO-1, MAGEA4, PRAME, Survivin and SSX. This will be done by using special types of T cells called cytotoxic T lymphocytes (CTLs) generated in the lab.
In addition, some adult patients will receive a drug called azacytidine before giving the T cells. We hope that the combination helps the T cells work better.
|Condition or disease||Intervention/treatment||Phase|
|Hodgkin Lymphoma Non-Hodgkin Lymphoma Hodgkin Disease||Biological: Antigen-Escalation Stage Biological: Dose-Escalation Stage Biological: azacytidine and multiTAA T cells Stage Biological: Pediatric multiTAA T cells Stage||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||36 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Administration of Tumor-Associated Antigen (TAA)-Specific Cytotoxic T-Lymphocytes to Patients With Active or Relapsed Hodgkin or Non-Hodgkin Lymphoma|
|Study Start Date :||January 2012|
|Actual Primary Completion Date :||September 27, 2021|
|Estimated Study Completion Date :||September 27, 2027|
Experimental: Antigen-Escalation Stage
The first stage will be an "antigen-escalation" stage using a fixed total dose of cells (5 x 10^6 cells/m^2 x 2) to evaluate the safety of the T cells primed against PRAME pepmix, and then SSX pepmix, and then MAGE A4 pepmix, and then NY-ESO pepmix, and then SURVIVIN pepmix.
Biological: Antigen-Escalation Stage
Each patient will receive 2 injections at the same dose (5 x 10^6 cells/m2), 28 days apart, according to the following schedules:
Experimental: Dose-Escalation Study Stage
In the dose escalation stage, three dose levels will be studied. Patients in the dose escalation portion of the study will be entered and stratified separately to the following two groups:
Group A: Patients receiving CTLs as therapy for Hodgkin's or non-Hodgkin's lymphoma.
Group B: Patients receiving CTLs as adjunctive therapy following autologous or syngeneic transplant.
Biological: Dose-Escalation Stage
Three different dosing schedules will be evaluated. Each patient will receive 2 injections at the same dose, 14 days apart, according to the following dosing schedules:
DL1: Day 0 and Day 14: 5 x 10^6 cells/m^2
DL2: Day 0 and Day 14: 1 x 10^7 cells/m^2
DL3: Day 0 and Day 14: 2 x 10^7 cells/m^2
Other Name: TAA-CTL infusion
Experimental: azacytidine and multiTAA T cells Stage
This phase will administer aza intravenously at a dose of 75 mg/m2 after premedication with an anti-emetic such as ondansetron po or IV (up to a maximum dose of 16 mg ondansetron or equivalent). This phase will determine whether infusion of TAA-specific T cells (at dose level 2 - 1x10^7) targeting multiple tumor antigens in combination with azacytidine is safe, and whether CTL infusions (with or without azacytidine) increase the spectrum of epitopes/antigens targeted by endogenous T cells (epitope spreading).
Biological: azacytidine and multiTAA T cells Stage
Up to 15 patients will be treated with 3 cycles of aza at a dose of 75 mg/m2 I.V. administered for 5 days/cycle followed, within 28 days of the last aza dose, by two infusions (on Day 0 and Day 14) of multi-TAA specific CTLs at a fixed dose of 1x10^7 cells/m2. If drug-related myelosuppression occurs aza dosing will be modified, according to the following:
Adjustment: Discontinue drug, can proceed with CTL infusion if eligible within 28 days of last aza infusion
Experimental: Pediatric multiTAA T cells Stage
This phase will give patients < 18 years old two infusions (on Day 0 and Day 14) of multi-TAA specific T cells at a fixed dose of 1x10^7 cells/m2. This phase will test the safety and efficacy of multiTAA-specific T cells in pediatric patients with active HL/NHL.
Biological: Pediatric multiTAA T cells Stage
Patients < 18 years old will receive two infusions (on Day 0 and Day 14) of multi-TAA specific T cells at a fixed dose of 1x10^7 cells/m2. We will enroll and infuse at least 5 adolescents on the pediatric arm before opening to all patients.
- Assessment of patients with adverse events [ Time Frame: 8 weeks ]To determine the safety of 2 intravenous injections of autologous TAA-specific cytotoxic T lymphocytes (CTLs) in patients with Hodgkin or non-Hodgkin lymphoma.
- Number of Patients with treatment related Serious Adverse Events [ Time Frame: 8 weeks ]To determine whether infusion of TAA-specific T cells targeting multiple tumor antigens in combination with azacytidine is safe
- Obtain information on the expansion, persistence and anti-tumor effects of the adoptively-transferred TAA-specific CTLs [ Time Frame: 1 year ]Information on the expansion, persistence and anti-tumor effects of the adoptively transferred tumor-specific CTLs will be analyzed for the immunological parameters based on multimer analysis, intracellular cytokine staining and ELIspot assays to assess the frequency of cells secreting γ-IFN using the descriptive statistics such as mean, median, standard deviation at each timepoint.
- Assessment of increasing the spectrum of epitopes/antigens [ Time Frame: 1 year ]To determine whether CTL infusions increase the spectrum of epitopes/antigens targeted by endogenous T cells (epitope spreading).
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): NCT01333046
|United States, Texas|
|Houston Methodist Hospital|
|Houston, Texas, United States, 77030|
|Texas Children's Hospital|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Geoge Carrum, MD||Baylor College of Medicine|