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Chimeric Antigen Receptor T-cells for The Treatment of AML Expressing CLL-1 Antigen

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04219163
Recruitment Status : Recruiting
First Posted : January 6, 2020
Last Update Posted : September 1, 2020
Sponsor:
Collaborators:
The Methodist Hospital System
Center for Cell and Gene Therapy, Baylor College of Medicine
Information provided by (Responsible Party):
LaQuisa Hill, Baylor College of Medicine

Brief Summary:

Patients eligible for this study have a type of blood cancer Acute Myeloid Leukemia (AML) which has come back or has not gone away after treatment.

The body has different ways of fighting disease and infection, and this research study combines two different ways of fighting cancer with antibodies and T cells with the hope that they will work together. T cells (also called T lymphocytes) are special infection-fighting blood cells that can kill other cells including tumor cells. Antibodies are types of proteins that protect the body from bacterial and other infectious diseases. Both antibodies and T cells have been used to treat patients with cancers; they have shown promise, but have not been strong enough to cure most patients when used alone.

T lymphocytes can kill tumor cells but there normally are not enough of them to kill all the tumor cells. Some researchers have taken T cells from a person's blood, grown more of them in the laboratory and then given them back to the person. The antibody used in this study targets CLL-1. This antibody sticks to AML cells because of a substance (protein) on the outside of these cells called CLL-1. For this study, the antibody to CLL-1 has been changed so that instead of floating free in the blood, it is now joined to the T cells. When T-cells contain an antibody that is joined to them, they are called chimeric antigen receptor T-cells or CAR-T cells.

In the laboratory, the investigators have also found that T cells work better if proteins that stimulate T cells are also added, such as one called CD28. Adding the CD28 makes the cells grow better and last longer in the body, thus giving the cells a better chance of killing the leukemia or lymphoma cells. In this study we are going to attach the CLL-1 chimeric receptor that has CD28 added to it to the patient's T cells. We will then test how long the cells last.

These CLL-1 chimeric antigen receptor T cells with CD28 are investigational products not approved by the Food and Drug Administration.


Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Biological: CLL-1.CAR T cells Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Chimeric Antigen Receptor T-cells for The Treatment of Acute Myeloid Leukemia Expressing CLL-1 Antigen
Actual Study Start Date : July 9, 2020
Estimated Primary Completion Date : July 31, 2024
Estimated Study Completion Date : July 31, 2038


Arm Intervention/treatment
Experimental: CLL-1.CAR
Group A
Biological: CLL-1.CAR T cells

Dose escalation study with 3 dose levels:

DL1: 1x 10^7 cells/m^2, DL2: 3x10^7 cells/m^2, DL3: 1x 10^8 cells/m^2

If excessive dose limiting toxicity attributed to the product occurs at dose level one, we will request permission from FDA to treat at dose level -1: 5×106 cells/m2





Primary Outcome Measures :
  1. Dose limiting toxicity (DLT) rate [ Time Frame: 4 weeks post T cell infusion ]
    To assess dose limiting toxicities per protocol-defined CLL-1.CAR T related adverse events and CTCAE v5.0


Secondary Outcome Measures :
  1. Overall Response Rate [ Time Frame: 4 weeks post T cell infusion ]
    To measure the anti-tumor effects of CLL-1.CAR T-cells in patients with acute myeloid malignancies.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 74 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

PROCUREMENT

Inclusion Criteria:

  1. Diagnosis of primary refractory or relapsed Acute Myeloid Leukemia (AML) AND suitable for consideration of allogeneic Hematopoietic Stem Cell Transplant with confirmation of an identified eligible donor by a FACT accredited transplant center and with confirmation that the center plans to proceed with transplant if CLL-1.CAR treatment induces response they consider adequate to proceed to allogeneic HSCT
  2. CLL-1 positive tumor with at least 30% CLL-1 blasts by flow cytometry or immunohistochemistry (tissue) assessed by a CLIA certified Flow Cytometry/Pathology laboratory
  3. Age ≤75 years NOTE: The first six (6) patients treated on the study will be adults (≥18 yrs of age).
  4. Hgb ≥ 7.0 g/dL(can be transfused)
  5. Life expectancy greater than 12 wks
  6. If apheresis required to collect blood

    • PT and APTT <1.5x ULN
    • Serum Creatinine < 1.5 x ULN
    • AST < 1.5 x ULN
  7. Informed consent

Exclusion Criteria:

  1. Active infection (bacterial, fungal or viral) requiring ongoing treatment without improvement.
  2. Active infection with HIV or HTLV
  3. Active second cancer (except non-melanoma skin cancer or in situ breast cancer or cervix cancer)or other cancer treated ≤ 2 years prior to enrollment
  4. Ongoing treatment with immune suppression for prophylaxis or treatment of GVHD including high dose steroids (eg prednisone > 0.25mg/kg)

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TREATMENT

Inclusion Criteria:

  1. Diagnosis of primary refractory or relapsed Acute Myeloid Leukemia (AML). Patients with targetable mutations should have failed or be ineligible for targeted therapies (e.g. FLT3 inhibitors, IDH inhibitors, or anti-CD33 drug conjugate). AND patients should be suitable for consideration of allogeneic Hematopoietic Stem Cell Transplant with confirmation of an identified eligible donor by a FACT accredited transplant center and with confirmation that the center plans to proceed with transplant if CLL-1.CAR treatment induces a response they consider adequate to proceed to allogeneic HSCT.
  2. CLL-1 positive tumor with at least 30% CLL-1 blasts by flow cytometry or immunohistochemistry (tissue) assessed by a CLIA certified Flow Cytometry/Pathology laboratory
  3. Age ≤75 years NOTE: The first six (6) patients treated on the study will be adults (≥18 yrs of age).
  4. AST/ALT less than 5 times the upper limit of normal
  5. Bilirubin less than 3 times the upper limit of normal
  6. Estimated GFR ≥ 60ml/min
  7. Pulse oximetry of > 92% on room air
  8. Karnofsky/Lansky ≥ 60
  9. Recovered from all acute toxic effects of prior chemotherapy at least one week before study entry and off systemic chemotherapy at least 2 weeks prior to study entry
  10. Available autologous transduced activated peripheral blood T-cell product with ≥ 20% expression of CLL-1.CAR.28z by flow cytometry
  11. Life expectancy > 12 weeks
  12. Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after the study is concluded. The male partner should use a condom
  13. Informed consent explained to, understood by, and signed by patient/guardian. Patient/guardian given copy of informed consent.

Exclusion Criteria:

  1. Currently receiving any investigational agents or having received any tumor vaccines within the previous 6 weeks.
  2. History of hypersensitivity reactions to murine protein-containing products.
  3. Pregnant or lactating.
  4. Active infection with HIV or HTLV.
  5. Clinically significant bacterial, viral or fungal infection requiring ongoing antifungal therapy without improvement,.
  6. Cardiac criteria: Prolonged QTc with maximum interval as defined by age with ; Uncontrolled atrial fibrillation/flutter; Myocardial infarction within the last 6 months; Cardiac echocardiography with LVSF<30% or LVEF<50% or clinically significant pericardial effusion; Cardiac dysfunction NYHA III or IV; CNS abnormalities: Presence of CNS disease defined as detectable cerebrospinal blast cells in a sample of CSF with ≥ 5 WBCs per mm3 or chloroma on imaging, History or presence of an underlying CNS disorder such as a seizure disorder requiring current use of antiepileptic medications, cerebrovascular ischemia/hemorrhage within prior 6 months, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
  7. Use of serotherapy with Campath or Anti-Thymocyte Globulin (ATG) within the last 28 days
  8. Use of Donor Lymphocyte Infusion (DLI) or other cellular therapy product within 30 days
  9. Acute GVHD ≥ Grade 2 or moderate to severe (formerly extensive) chronic GVHD
  10. Aministration of high dose steroids >1 mg/kg within the preceding 5 days or currently receiving > 0.25 mg/kg of Prednisone equivalent
  11. Hyperleukocytosis (WBC ≥50K) or rapidly progressive disease that in the estimation of the investigator would compromise the ability of the patient to complete the study.

Information from the National Library of Medicine

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): NCT04219163


Contacts
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Contact: LaQuisa Hill, MD 713-441-1450 LaQuisa.Hill@bcm.edu

Locations
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United States, Texas
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: LaQuisa Hill, MD    713-441-1450    LaQuisa.Hill@bcm.edu   
Sponsors and Collaborators
Baylor College of Medicine
The Methodist Hospital System
Center for Cell and Gene Therapy, Baylor College of Medicine
Investigators
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Principal Investigator: LaQuisa Hill, MD Cell and Gene Therapy, Baylor College of Medicine
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Responsible Party: LaQuisa Hill, Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT04219163    
Other Study ID Numbers: H-43516-CARMEN
First Posted: January 6, 2020    Key Record Dates
Last Update Posted: September 1, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by LaQuisa Hill, Baylor College of Medicine:
AML
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms