Using engineered T-cells to treat relapsed Acute Myeloid Leukemia

Chimeric Antigen Receptor T-cells for the Treatment of Acute Myeloid Leukemia Expressing CLL-1 Antigen

This study is testing if specially engineered T-cells can help people with relapsed Acute Myeloid Leukemia feel better after they receive a stem cell transplant.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: N/A to 75 Years
• Sex: All
• Sponsor: Baylor College of Medicine (other)
• Drugs / interventions: chemotherapy, prednisone, CAR-T, chimeric antigen receptor, cyclophosphamide, fludarabine
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT04219163 on ClinicalTrials.gov

What this trial studies

This clinical trial focuses on patients with relapsed or refractory Acute Myeloid Leukemia (AML) who are suitable for allogeneic Hematopoietic Stem Cell Transplant. The study involves collecting the patient's blood to create CLL-1 chimeric antigen receptor T-cells, which are then infused back into the patient after a chemotherapy regimen to reduce existing T-cell levels. The goal is to enhance the effectiveness of these engineered T-cells in targeting and killing AML cells. Patients will be monitored for long-term effects of this gene transfer for up to 15 years.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with relapsed or refractory AML expressing the CLL-1 antigen.

Not a fit: Patients with acute promyelocytic leukemia or active infections requiring treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a new treatment option for patients with difficult-to-treat AML.

How similar studies have performed: Other studies using CAR T-cell therapies have shown promise in treating various cancers, indicating potential for success with this approach.

Eligibility criteria

PROCUREMENT

Inclusion Criteria:

1. 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
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. Diagnosis of acute promyelocytic leukemia (APL)
2. Active infection (bacterial, fungal or viral) requiring ongoing treatment without improvement.
3. Active infection with HIV or HTLV (results may be pending)
4. 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
5. Ongoing treatment with immune suppression for prophylaxis or treatment of GVHD including high dose steroids (e.g. prednisone \> 0.25mg/kg)

TREATMENT

Inclusion Criteria:

1. 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.
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. 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
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. Diagnosis of acute promyelocytic leukemia (APL)
2. Currently receiving any investigational agents or having received any tumor vaccines within the previous 6 weeks.
3. History of hypersensitivity reactions to murine protein-containing products.
4. Pregnant or lactating.
5. Active infection with HIV or HTLV.
6. Clinically significant bacterial, viral or fungal infection requiring ongoing antifungal therapy without improvement,.
7. Fever of unknown origin without complete work-up including imaging (CT head, sinus, chest, abdomen/pelvis)
8. Cardiac criteria: Prolonged QTc with maximum interval as defined by age; Uncontrolled atrial fibrillation/flutter; Myocardial infarction; Cardiac echocardiography with LVSF\<30% or LVEF\<50% or clinically significant pericardial effusion; Cardiac dysfunction NYHA III or IV; Confirmation of absence of these conditions within 6 months of treatment.
9. CNS abnormalities: Presence of CNS disease defined as detectable cerebrospinal blast cells in a sample of CSF with ≥ 5 WBCs per mm\^3 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.
10. Use of serotherapy with Campath or Anti-Thymocyte Globulin (ATG) within the last 28 days
11. Use of Donor Lymphocyte Infusion (DLI) or other cellular therapy product within 30 days
12. Acute GVHD ≥ Grade 2 or moderate to severe (formerly extensive) chronic GVHD
13. Administration of high dose steroids \>1 mg/kg within the preceding 5 days or currently receiving \> 0.25 mg/kg of Prednisone equivalent
14. 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.

Where this trial is running

Houston, Texas

• Texas Children's Hospital — Houston, Texas, United States (RECRUITING)

Study contacts

• Principal investigator: LaQuisa Hill, MD — Cell and Gene Therapy, Baylor College of Medicine
• Study coordinator: LaQuisa Hill, MD

Conditions: Acute Myeloid Leukemia, AML