Donor Lymphocyte Infusion (DLI) of T-cells Genetically Modified With iCasp9 Suicide Gene
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|ClinicalTrials.gov Identifier: NCT01875237|
Recruitment Status : Terminated
First Posted : June 11, 2013
Results First Posted : July 16, 2019
Last Update Posted : July 16, 2019
The goal of this clinical research study is to learn if giving genetically changed immune cells, called T-cells, after chemotherapy will improve the response to a stem cell transplant. The safety of this treatment will also be studied.
The process of changing the DNA (the genetic material in cells) of these T-cells is called "gene transfer." Researchers want to learn if these genetically-changed T-cells are effective in attacking cancer cells in patients with leukemia, MDS, lymphoma, Hodgkin disease, or MM, after they have received an allogeneic stem cell transplant.
The chemotherapy you will be given on study is fludarabine, melphalan, and alemtuzumab. These drugs are designed to stop the growth of cancer cells, which may cause the cancer cells to die. This chemotherapy is also designed to block your body's ability to reject the donor's stem cells.
Researchers also want to learn if giving AP1903 will help the symptoms of graft-versus-host disease (GvHD) that may occur after the T-cell infusion. GvHD occurs when donor cells attack the cells of the person receiving the stem cell transplant.
|Condition or disease||Intervention/treatment||Phase|
|Leukemia Myeloma Myeloproliferative Diseases||Drug: Fludarabine Drug: Melphalan Drug: Alemtuzumab Procedure: Stem Cell infusion Drug: Tacrolimus Drug: Mini Methotrexate Drug: G-CSF Procedure: Donor Lymphocyte Infusion (DLI) Drug: AP1903 Drug: Methylprednisolone Behavioral: Questionnaire||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||3 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1/2 Trial Evaluating Treatment of Emergent Graft Versus Host Disease (GvHD) With AP1903 After Planned Donor Infusions (DLIs) of T-cells Genetically Modified With the iCasp9 Suicide Gene in Patients With Hematologic Malignancies|
|Actual Study Start Date :||December 27, 2013|
|Actual Primary Completion Date :||March 7, 2017|
|Actual Study Completion Date :||March 7, 2017|
Experimental: Stem Cell Transplant + Modified T-Cells + Chemotherapy
The first component is stem cell transplant. Goal is to administer more than 3 x 106 CD34+ cells/kg of peripheral blood progenitor cells (PBPC). The second component is the planned DLI infusion. iCasp9 (BPZ-1001)-Modified T-cells) of 3 X 10^6/kg in 100 ml infused over approximately a one hour period between Day + 56 to Day +64. The transplant day is referred to as day zero (D0), treatment plan activities prior or after D0 are denoted as day minus (D-) or day plus (D+). Patients receive standard reduced intensity regimen using fludarabine, melphalan, and alemtuzumab to achieve engraftment with a low risk of GVHD. At approximately 60 days post transplant patients who are alive and without GVHD, receive DLI to enhance graft-vs.-malignancy and immune reconstitution.
40 mg/m2 by vein on Days -6 to -3.
140 mg/m2 by vein on Day -2.
Other Name: Alkeran
50 mg by vein on Day -1.
Procedure: Stem Cell infusion
Stem cell infusion on Day 0. Goal is to administer more than 3 x 10^6 CD34+ cells/kg of peripheral blood progenitor cells (PBPC).
Starting dose of 0.015 mg/kg (ideal body weight) as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml) between Day +1 and Day +45. Tacrolimus is changed to oral dosing when tolerated. Tacrolimus tapering should start on approximately Day +35 with the intention for the patient to be completely off the drug by approximately Day +45.
Other Name: Prograf
Drug: Mini Methotrexate
5 mg/m2 by vein on Days +1, +3, +6.
5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until the absolute neutrophil count (ANC) is > 500 x 10/L for 3 consecutive days.
Procedure: Donor Lymphocyte Infusion (DLI)
iCasp9 (BPZ-1001)-Modified T-cells) of 3 X 10^6/kg in 100 ml infused over approximately a one hour period between Day + 56 to Day +64.
0.4 mg/kg as a 2 hour infusion for patients that present with a clinical diagnosis of grade I GvHD. For patients with a clinical diagnosis of grade > 2 GvHD, a single dose of AP1903 0.4 mg/kg as a 2 hour infusion will be administered. Patients who fail to achieve a complete response within 72 hours of an initial dose of AP1903, or within 48 hours of a second dose of AP1903, will be maintained on this dose for no less than 7 days. Patients who experience a partial response within 72 hours may receive a second dose of AP1903. Patients whose GvHD is progressing after 7 days, have no response by 14 days, or are not in a complete response at day 28 can receive secondary therapy.
1.6 mg/kg per day by vein divided in 2 to 3 daily doses. Patients whose GvHD resolves as defined by a complete response within 72 hours, would have steroids stopped immediately. Patients who fail to achieve a complete response within 72 hours of an initial dose of AP1903, or within 48 hours of a second dose of AP1903, will be maintained on this dose for no less than 7 days. Steroids can then be tapered as tolerated to no less than 0.6 mg/kg per day at day 28.
Completion of a quality of life questionnaire that will take 10-15 minutes between Days + 28 and + 56, about twice a week until about 2 months after the T-cell infusion, and then 6 and 12 months after the stem cell transplant.
Other Name: Survey
- To Evaluate the Safety of Donor Lymphocyte Infusion Followed by Dimerizer Drug, AP1903 by Number of Participants With Adverse Events. [ Time Frame: up to 3.5 years ]To evaluate the safety of the infusion of inducible caspase 9 (BPZ-1001) modified T-cells followed by dimerizer drug, AP1903. Safety evaluated by number of participants with Adverse events.
- Number of Participants Assessed Post Donor Lymphocyte Infusion (DLI): Disease-free Survival & Non-relapse Mortality, Chimerism and GVHD. [ Time Frame: 6 months ]Participants to assess at 6 months post donor lymphocyte infusion (DLI): disease-free survival & non-relapse mortality, chimerism and GVHD
- To Assess the Incidence of Epstein-Barr Virus -PTLD or EBV Reactivation Requiring Therapy Post DLI. [ Time Frame: 1 year ]To assess the incidence of Epstein-Barr virus (EBV)-associated lymphoproliferative disorder or EBV reactivation requiring therapy post DLI.
- To Assess the Proportion of Patients Developing Grade I-IV Acute GvHD [ Time Frame: Day 28, 56, and 180 post DLI. ]To assess the proportion of patients developing grade I-IV acute GvHD by Day 28, 56, and 180 post DLI.
- To Assess the Proportions of GvHD Response Post-administration of AP1903. [ Time Frame: Day 3, 7, 14, 28, and 56 post-administration of AP1903 ]To assess the proportions of GvHD complete response (CR), partial response (PR), mixed response, no response, and progression among surviving patients at Day 3, 7, 14, 28, and 56 post-administration of AP1903.
- To Assess the Incidence of GvHD Treatment Failure Post-administration of AP1903. [ Time Frame: Day 3, 7, 14, 28, and 56 post-administration of AP1903. ]To assess the incidence of GvHD treatment failure, defined as no response, progression, administration of additional therapy for GvHD, or mortality post-administration of AP1903.
- To Assess the Incidence of Acute GvHD Flare After CR/PR Requiring Additional Agent for Systemic Therapy Before Day 56 Post-administration of AP1903. [ Time Frame: before Day 56 post AP1903 ]To assess participants with incidence of acute GvHD flare after CR/PR requiring additional agent (including 2.5 mg/kg/day of prednisone [or methylprednisolone equivalent of 2 mg/kg/day]) for systemic therapy before Day 56 post-administration of AP1903."
- To Assess Post Donor Lymphocyte Infusion (DLI) Chimerism [ Time Frame: 6 months ]To assess the number of Participants with 100% donor chimerism at 6 months post donor lymphocyte infusion (DLI)
- To Assess Presence of Gvhd Post Donor Lymphocyte Infusion (DLI) [ Time Frame: 6 months ]To assess at 6 months post donor lymphocyte infusion (DLI): GVHD grade & time to resolution
- To Determine the Change in Patient-reported Outcomes [ Time Frame: Day 56 post administration of AP1903 ]To determine the change in patient-reported outcomes from enrollment to day 56 post administration of AP1903, through the patient quality of life survey.
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): NCT01875237
|United States, Texas|
|University of Texas MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Richard E. Champlin, MD, BS||M.D. Anderson Cancer Center|