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

NCT04219163 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: H-43516-CARMEN52988-C1
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Myeloid Leukemia

Keywords

AML

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity (DLT) rate

  To assess dose limiting toxicities per protocol-defined CLL-1.CAR T related adverse events and CTCAE v5.0

  4 weeks post T cell infusion

Secondary Outcomes (1)

• Overall Response Rate

  4 weeks post T cell infusion

Study Arms (1)

CLL-1.CAR

EXPERIMENTAL

Group A

Biological: CLL-1.CAR T cells

Interventions

CLL-1.CAR T cells BIOLOGICAL

Dose escalation study with 3 dose levels: DL1: 1x10\^7 cells/m2, DL2: 3x10\^7 cells/m2, DL3: 1x10\^8 cells/m2 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: 5×10\^6 cells/m2

CLL-1.CAR

Eligibility Criteria

• Age: Up to 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of primary refractory or relapsed Acute Myeloid Leukemia (AML) with the exception of acute promyelocytic leukemia (APL) AND suitable for consideration of allogeneic Hematopoietic Stem Cell Transplant with confirmation of an identified eligible donor by a FACT accredited transplant center
• 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
• Age ≤75 years NOTE: The first six (6) patients treated on the study will be adults (≥18 yrs of age).
• Hgb ≥ 7.0 g/dL(can be transfused)
• Life expectancy greater than 12 wks
• If apheresis required to collect blood
• PT and APTT \<1.5x ULN
• Serum Creatinine \< 1.5 x ULN
• AST \< 1.5 x ULN
• Informed consent

You may not qualify if:

• Diagnosis of acute promyelocytic leukemia (APL)
• Active infection (bacterial, fungal or viral) requiring ongoing treatment without improvement.
• Active infection with HIV or HTLV (results may be pending)
• 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
• Ongoing treatment with immune suppression for prophylaxis or treatment of GVHD including high dose steroids (e.g. prednisone \> 0.25mg/kg)
• TREATMENT
• Diagnosis of primary refractory or relapsed Acute Myeloid Leukemia (AML) with the exception of acute promyelocytic leukemia (APL). 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.
• 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
• Age ≤75 years NOTE: The first six (6) patients treated on the study will be adults (≥18 yrs of age).
• AST/ALT less than 5 times the upper limit of normal
• Bilirubin less than 3 times the upper limit of normal
• Estimated GFR ≥ 60ml/min
• Pulse oximetry of \> 92% on room air
• Karnofsky/Lansky ≥ 60
• No systemic chemotherapy at least 2 weeks prior to treatment on study and must be recovered from all acute toxic effects of prior chemotherapy at time of treatment

Sponsors & Collaborators

• Baylor College of Medicine: lead
• The Methodist Hospital Research Institute: collaborator
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator

Study Sites (1)

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• LaQuisa Hill, MD

  Cell and Gene Therapy, Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 3, 2020
• First Posted: January 6, 2020
• Study Start: July 9, 2020
• Primary Completion: March 24, 2025
• Study Completion (Estimated): July 31, 2038
• Last Updated: September 22, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)