Clinical Study of Anti-FLT3 CAR-T Cells for the Treatment of Relapsed/Refractory AML
Phase 1 Study of Anti-FLT3 Chimeric Antigen Receptor-redirected T Cells in Subjects With Relapsed/Refractory Acute Myeloid Leukemia (AML)
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 12 Years and older
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
- Procedures mentioned: Infusions
Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.
Show the study's own words
- "Evaluable subjects are defined as those who have received an infusion of HG-CT-1."
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This phase 1 study tests the safety of HG-CT-1, an anti-FLT3 CAR-T cell treatment, at different doses. It is for adults and some children ages 12–17 with acute myeloid leukemia (AML), a blood cancer that came back or did not respond to treatment. The study will also check how well the treatment works.
This is a phase 1 dose escalation study to determine the safety of anti-FLT3 CAR-T in subjects with R/R AML. The primary objective is to assess safety. Up to 18 evaluable adult and 18 evaluable pediatric subjects will be enrolled. Evaluable subjects are defined as those who have received an infusion of HG-CT-1. Primary clinical objectives: i. Determine the safety of HG-CT-1 based on the proportion of subjects infused with HG-CT-1 who experience a dose limiting toxicity (DLT). Secondary clinical objectives: i. Estimate the efficacy of HG-CT-1 according to standard clinical response criteria for AML. ii. Estimate overall survival of evaluable subjects. iii. Estimate progression-free survival of evaluable subjects. iv. Estimate duration of response in evaluable subjects who achieve a response. Secondary scientific objectives: i. Describe the persistence and trafficking of HG-CT-1. ii. Describe HG-CT-1 bioactivity and its predictors.
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- Be age 18 or older. Children ages 12–17 who weigh at least 35 kg may join only after safety checks at the same dose in adults are complete.
- Have AML unlikely to be cured with current treatments. It must have resisted two rounds of specified treatment; returned after a donor stem cell transplant; returned within 12 months of initial treatment; returned later and resisted another treatment round; or returned at least twice.
- If AML resisted initial treatment and has certain gene changes, specific drugs must also have failed: an FLT3 inhibitor for FLT3 ITD, ivosidenib for IDH1, or enasidenib for IDH2.
- Tests must find the FLT3 protein on the leukemia cells. Have a suitable stem cell donor who is cleared to donate before study treatment.
- If AML returned after a donor transplant, be off medicines that suppress the immune system for at least one month. Have no graft-versus-host disease (donor cells attacking your body) that needs these medicines.
- Meet the study’s kidney, liver, heart, and lung test limits.
- Meet activity score limits: ECOG 0–1 for adults, meaning fully active or limited only in hard physical activity; Lansky/Karnofsky at least 50 for children.
- Give written consent, or have a parent or legal guardian give consent when needed. Children ages 12–17 also receive agreement forms. Use acceptable birth control if able to have children.
Who can't join
- Be pregnant or breastfeeding.
- Have another active cancer, with exceptions for certain early cervical cancers, slow-growing prostate cancer that has not spread, non-melanoma skin cancer, or other slow-growing, controlled cancers not needing urgent treatment.
- Have had a donor stem cell transplant less than 100 days ago, active graft-versus-host disease while taking immune-suppressing treatment, or a donor lymphocyte infusion (donor immune cells) within 30 days.
- Have active hepatitis B or C, any HIV infection, or another active or uncontrolled infection. Past hepatitis B, properly treated hepatitis C, and controlled infections on treatment may be allowed.
- Take steroids above the study’s dose limits or other medicines that suppress the immune system. Inhaled steroids are allowed.
- Have an uncontrolled illness, mental health condition, or social situation that makes study participation unsafe or hard to complete. Active leukemia in the brain or spinal cord also excludes you; previously treated disease may be allowed if tests show it has cleared.
- Have a known allergy to human serum albumin, DMSO, or Dextran 40, which are ingredients in the study treatment.
- Have acute promyelocytic leukemia, more than 50,000 leukemia blast cells per microliter of blood, or disease worsening so fast that study treatment may not be completed.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
Inclusion Criteria: * 18 years of age or older at enrollment. Patients ≥12 and \<18 12 to 17 years of age weighing ≥ 35 kg at enrollment may be included once safety evaluation at the corresponding adult dose escalation protocol have been completed. * Subjects with AML unlikely to be cured with currently available therapies. Specifically, the following groups are eligible: 1. Refractory AML: i.e., newly diagnosed AML that after two cycles of intensive chemotherapy has not achieved a complete remission or morphologic leukemia free state by ELN criteria.1 Intensive chemotherapy must have included either the combination of cytarabine and an anthracycline (7+3 or similar) or combination of venetoclax with a hypomethylating agent. Patients with FLT3 ITD must also have failed treatment with a FLT3 inhibitor and patients with IDH1 or IDH2 mutations must have failed treatment containing ivosidenib or enasidenib respectively (i.e., progression on treatment, or failure to achieve CR after six months of treatment,) OR: 2. AML relapsed following allogeneic stem cell transplantation (including MDS evolved to AML post-allogeneic stem cell transplantation). Note: morphologic relapse is not required; persistent/recurrent disease-associated molecular, phenotypic, or cytogenetic abnormalities (measurable residual disease, MRD) at any time after allogeneic HSCT is eligible. OR: 3. AML that has relapsed within 12 months after initial induction and consolidation therapy OR: 4. AML that has relapsed more than 12 months after initial induction but that has failed to achieve CR or morphologic leukemia free state after one reinduction OR: 5. AML after second or subsequent relapse. * FLT3 expression must be detectable in AML blast by flow cytometric analysis. * Subjects must have a suitable stem cell transplant donor. Donor may be matched or mismatched and must be found to be suitable according to the institution's standard criteria. That donor shall be "cleared" for donation by institutional standards prior to administration of HG-CT-1. Adult donors can be either related or unrelated, HLA-matched or partially matched. Matched or partially matched umbilical cord blood donors are also eligible. * Subjects with relapsed disease after prior allogeneic transplant must be off systemic immunosuppression for at least 1 month at the time of enrollment without GvHD that requires systemic immunosuppression. * Satisfactory organ functions: 1. Creatinine ≤ 1.6 mg/dl and Creatinine clearance (CrCl) as calculated by the Cockcroft-Gault formula ≥ 60 mL/min. 2. ALT/AST must be ≤ 3 x upper limit of normal unless related to disease. 3. Direct bilirubin \< 2.0mg/dl unless subject has Gilbert's syndrome (in which case it should be ≤3.0 mg/dL). 4. Left ventricular ejection fraction ≥ 45% as confirmed by echocardiogram or MUGA. 5. DLCO \>45% predicted and O2 Saturation \> 90% on room air. * Patients ≥18 must have an ECOG Performance status 0-1. Patients \<18 must have a Lansky/Karnofsky score of ≥50. * Written informed consent is given in patients ≥ 18. In patients \<18 or not developmentally appropriate for consent, written consent will be provided to the parent or legal guardian. Patients ≥12 and \<18 years of age will be additionally provided with assent documentation. * Subjects of reproductive potential must agree to use acceptable birth control methods (as described in protocol Section 4.7). Exclusion Criteria: * Pregnant or lactating (nursing) women. * Active second malignancy will not be eligible with the following exceptions: 1. Carcinoma in situ of the cervix (which may be considered for enrollment), 2. Indolent, non-metastatic prostate cancer 3. Non melanoma skin cancer 4. Other indolent and controlled malignancies not requiring urgent treatment. * Subjects with a history of a prior allogeneic stem cell transplantation are excluded if: 1. Subjects are less than 100 days post-transplant OR 2. Subjects have evidence of ongoing active GvHD and are taking immunosuppressive agents (\>0.5mg/kg/methylprednisolone equivalents or other immunosuppression for GvHD treatment) OR 3. Subjects have received DLI within 30 days prior to enrollment. * Active hepatitis B (HBV) or active hepatitis C (HCV) or any HIV infection. Note: prior HCV that has been appropriately treated or evidence of past HBV infection do not constitute exclusions. * Concurrent use of systemic steroids at a prednisone dose of greater than 10 mg, hydrocortisone greater than 10-12.5 mg/m2/day, or equivalent. Recent, or current use of inhaled steroids is not exclusionary. * Concurrent use of immunosuppressant medications such as calcineurin inhibitors, methotrexate, or alemtuzumab. * Uncontrolled, symptomatic, intercurrent illness including but not limited to infection, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness, or social situations that would limit compliance with study requirements or in the opinion of the site Pl would pose an unacceptable risk to the subject. * Active or uncontrolled viral, bacterial, or fungal infection. May be receiving ongoing therapy for controlled infection. * Subjects with signs or symptoms indicative of active CNS involvement. A CNS evaluation shall be performed as clinically appropriate to rule out CNS involvement. Subjects with adequately treated CNS leukemia are eligible. History of CNS involvement is not exclusionary if CNS has been cleared with a documented negative lumbar puncture and negative imaging (imaging required only if previously showing evidence of CNS leukemia not otherwise documented by spinal fluid assessment). * Known history of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40). * Hyperleukocytosis (\>50,000 blasts/µL) or rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy. * Patients with Acute Promyelocytic Leukemia are not eligible.
Study sites (1)
TX
- MD Anderson · Houston, TX 77030Nicholas Short · Study contact · 1-877-632-6789 · nshort@mdanderson.orgMore trials in Houston