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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

NCT03126864

Description:

Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential participant. 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.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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
  • Official Title: A Phase 1 Safety 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

Clinical Trial IDs

  • ORG STUDY ID: 2016-0341
  • SECONDARY ID: NCI-2018-01167
  • NCT ID: NCT03126864

Conditions

  • Hematopoietic/Lymphoid Cancer
  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
FludarabineFludarabine Phosphate, FludaraCD33-CAR-T cells - Adult Group
CyclophosphamideCytoxan, NeosarCD33-CAR-T cells - Adult Group
CD33-CAR-T Cell InfusionCD33-CAR-T cells - Adult Group

Purpose

Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential participant. 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.

Trial Arms

NameTypeDescriptionInterventions
CD33-CAR-T cells - Adult GroupExperimentalAfter 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.
  • Fludarabine
  • Cyclophosphamide
CD33-CAR-T cells - Pediatric GroupExperimentalAfter 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.
  • Fludarabine
  • Cyclophosphamide

Eligibility Criteria

        Inclusion Criteria:

          1. Age 1-80 years of age. The pediatric cohort is defined as age younger than 18 years.

          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:

          1. Diagnosis of acute promyelocytic leukemia (APL M3): t(15;17)(q22;q12); (promyelocytic
             leukemia [PML]/retinoic acid receptor [RAR] alpha [a]) and variants excluded.

          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.
      
Maximum Eligible Age:80 Years
Minimum Eligible Age:1 Year
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended Phase II Dose (RP2D) of CD33-CAR-T Cells
Time Frame:28 days after completion of the CD33-CAR-T infusion
Safety Issue:
Description:RP2D defined as the highest dose level in which 6 patients have been treated with at most 1 instance of dose limiting toxicity (DLT). DLT is defined as a clinically significant adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications and occurring during the first course on study that meets any of the following criteria: CTCAE grades non-reversible grade 3, or any grade 4-5 allergic reactions related to the study cell infusion. CTCAE grades non-reversible grade 3, or any grade 4-5 autoimmune reactions related to the study cell infusion. CTCAE grades non-reversible grade 3, or any grade 4-5 organ toxicity (cardiac, dermatologic, gastrointestinal, hepatic, pulmonary, renal/genitourinary, or neurologic) not pre-existing or due to the underlying malignancy and occurring within 28 days of study product infusion related to study cell infusion.

Secondary Outcome Measures

Measure:Disease Response to CD33-CAR-T Cells
Time Frame:On Day 7, at Weeks 2, 4, and 8, and at Months 3, 6, and 12 after CD33-CAR-T Cell infusion
Safety Issue:
Description:Response to treatment evaluated according to the World Health Organization (WHO) standardized response criteria for myelodysplastic syndromes. Disease response to CD33-CAR-T cells defined as Complete Remission (CR), Complete Remission without Platelet Recovery (CRp), Complete Remission without Neutrophil Recovery (CRn), Complete Remission with Incomplete Blood Count Recovery (CRi), Partial Remission (PR) or Non-responder (NR).

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Hematopoietic/Lymphoid Cancer
  • Acute Myeloid Leukemia
  • AML
  • Relapsed or Refractory CD33-Positive
  • CD33-CAR-T cells
  • Fludarabine
  • Fludarabine phosphate
  • Fludara
  • Cyclophosphamide
  • Cytoxan
  • Neosar

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