Study of Adoptive Cellular Therapy Using Autologous T Cells Transduced With Lentivirus to Express a CD33 Specific Chimeric Antigen Receptor in Patients With Relapsed or Refractory CD33-Positive Acute Myeloid Leukemia
NCT ID: NCT03126864
Last Updated: 2019-11-04
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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TERMINATED
PHASE1
11 participants
INTERVENTIONAL
2017-08-04
2019-10-10
Brief Summary
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The goal of this clinical research study is to learn about the safety and tolerability of 3 different doses of CD33-CAR-T cells (referred to throughout the consent as "T-cells") in patients who have CD33-positive acute myeloid leukemia (AML) that is relapsed (has come back) or refractory (has not responded to treatment).
CD33-CAR-T is made by genetically modifying (changing) your T-cells (a type of white blood cell). T-cells are genetically changed to help target leukemia cells.
This is an investigational study. CD33-CAR-T is not FDA approved or commercially available. It is currently being used for research purposes only. The study doctor can explain how the study drug is designed to work.
Up to 39 participants will be enrolled in this study. All will take part at MD Anderson.
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Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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CD33-CAR-T cells - Adult Group
After enrollment, steady state leukapheresis performed to collect apheresis material.
Fludarabine administered by vein on Days -5 to -3.
Cyclophosphamide administered by vein on Day -3.
CD33-CAR-T cell infusion administered by vein on Day 0. First group of participants receive the lowest dose level. Each new group will receive a higher dose than the one before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of T-cells is found.
Leukapheresis
After enrollment, steady state leukapheresis performed to collect apheresis material. The goal is to achieve a target total nucleated cell (TNC) yield of at least 5 x 10\^9 (expected range 5 x 10\^8 - 5 x 10\^10), for up to two days.
Fludarabine
25 mg/m2 administered by vein on Days -5 to -3.
Cyclophosphamide
900 mg/m2 administered by vein on Day -3.
CD33-CAR-T Cell Infusion
CD33-CAR-T cell infusion administered by vein on Day 0. First group of participants receive the lowest dose level. Each new group will receive a higher dose than the one before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of T-cells is found. Starting dose level is \> 1.5 x 105/kg but ≤ 4.5 x 105/kg.
CD33-CAR-T cells - Pediatric Group
After enrollment, steady state leukapheresis performed to collect apheresis material.
Fludarabine administered by vein on Days -5 to -3.
Cyclophosphamide administered by vein on Day -3.
CD33-CAR-T cell infusion administered by vein on Day 0. First group of participants receive the lowest dose level. Each new group will receive a higher dose than the one before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of T-cells is found.
Leukapheresis
After enrollment, steady state leukapheresis performed to collect apheresis material. The goal is to achieve a target total nucleated cell (TNC) yield of at least 5 x 10\^9 (expected range 5 x 10\^8 - 5 x 10\^10), for up to two days.
Fludarabine
25 mg/m2 administered by vein on Days -5 to -3.
Cyclophosphamide
900 mg/m2 administered by vein on Day -3.
CD33-CAR-T Cell Infusion
CD33-CAR-T cell infusion administered by vein on Day 0. First group of participants receive the lowest dose level. Each new group will receive a higher dose than the one before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of T-cells is found. Starting dose level is \> 1.5 x 105/kg but ≤ 4.5 x 105/kg.
Interventions
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Leukapheresis
After enrollment, steady state leukapheresis performed to collect apheresis material. The goal is to achieve a target total nucleated cell (TNC) yield of at least 5 x 10\^9 (expected range 5 x 10\^8 - 5 x 10\^10), for up to two days.
Fludarabine
25 mg/m2 administered by vein on Days -5 to -3.
Cyclophosphamide
900 mg/m2 administered by vein on Day -3.
CD33-CAR-T Cell Infusion
CD33-CAR-T cell infusion administered by vein on Day 0. First group of participants receive the lowest dose level. Each new group will receive a higher dose than the one before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of T-cells is found. Starting dose level is \> 1.5 x 105/kg but ≤ 4.5 x 105/kg.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Patients with active (blood or bone marrow blasts \>5%) relapsed or refractory CD33+ acute myeloid leukemia (AML) de novo, or secondary. a. Relapsed AML is defined as patients that had a first complete remission (CR) before developing recurrent disease. b. Refractory AML defined as patients that have not achieved a CR after 2 cycles of induction chemotherapy.
3. Patients must have bone marrow and peripheral blood studies available for confirmation of diagnosis of AML; CD33 positivity must be confirmed by either flow cytometry or immunohistochemistry; cytogenetics, flow cytometry, and molecular studies (such as FMS-like tyrosine kinase-3 \[Flt-3\] status) will be obtained as per standard practice.
4. ECOG performance status score \</= 2.
5. Pretreatment calculated or measured creatinine clearance (absolute value) of \>= 60 mL/minute.
6. Serum bilirubin =\< 3.0 mg/dL.
7. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 5 times the institutional upper limits of normal.
8. Ejection fraction measured by echocardiogram (ECHO) or multi gated acquisition scan (MUGA) \>50%.
9. Subject does not require supplemental oxygen or mechanical ventilation, and oxygen saturation by pulse oximetry is 94% or higher on room air.
10. Negative serum pregnancy test.
11. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately.
12. Patients who have undergone allo-SCT are eligible if they are at least 3 months post SCT, have relapsed AML, are not on treatment or prophylaxis for GVHD, and have no active GVHD.
13. All patients or legally responsible parent or guardian must have the ability to understand and willingness to sign a written informed consent
Exclusion Criteria
2. Patients with extramedullary disease as their sole site of relapsed AML.
3. Acceptable allogeneic stem cell donor with imminent plans to proceed with allo-SCT.
4. Known central nervous system (CNS) leukemic involvement that is refractory to intrathecal chemotherapy and/or cranio-spinal radiation; patients with a history of CNS disease that have been effectively treated to complete remission (\< 5 white blood cell \[WBC\]/mm\^3 and no blasts in cerebrospinal fluid \[CSF\]) will be eligible.
5. Ongoing or active or uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, poorly controlled pulmonary disease or psychiatric illness/social situations that would limit compliance with study requirements.
6. Human immunodeficiency virus (HIV) seropositivity, or active hepatitis B or C infection based on testing performed within 4 weeks of enrollment.
7. Currently enrolled in another investigational therapy protocol for AML.
8. Participants with presence of other active malignancy within 2 years of study entry; participants with history of prior malignancy treated with curative intent and achieved CR within 2 years are eligible.
9. Pregnant and lactating women are excluded from this study
10. Failure of research participant or legally responsible parent or guardian to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I study.
11. History of allergic reactions attributed to compounds of similar chemical or biological composition to cetuximab (anti-EGFR).
12. History of allergic reactions to products containing mouse and bovine protein antibodies.
13. Receiving corticosteroids at \>20 mg (age \>17) or \>0.5mg/kg (age \<18) daily prednisone dose or equivalent.
14. Active autoimmune disease requiring systemic immunosuppressive therapy.
15. Patient, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
1 Year
80 Years
ALL
No
Sponsors
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Intrexon Corporation
INDUSTRY
M.D. Anderson Cancer Center
OTHER
Responsible Party
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Principal Investigators
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William G. Wierda, MD, PHD, BS
Role: PRINCIPAL_INVESTIGATOR
M.D. Anderson Cancer Center
Locations
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University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Countries
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Related Links
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University of Texas MD Anderson Cancer Center Website
Other Identifiers
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NCI-2018-01167
Identifier Type: REGISTRY
Identifier Source: secondary_id
2016-0341
Identifier Type: -
Identifier Source: org_study_id
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