RECRUITING

Chimeric Antigen Receptor T Cell Redirected to Target CD4 Positive Relapsed Refractory Acute Myeloid Leukemia (AML ) As a Bridge to Allogeneic Stem Cell Transplant

Conditions

Acute Myeloid Leukemia T Cell Cell Therapy CAR T Chimeric Antigen Receptor Therapy

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This study is designed as a single arm open label traditional Phase I, 3+3, study of CD4-redirected chimeric antigen receptor engineered T-cells (CD4CAR) in patients with relapsed or refractory AML. The study will evaluate safety in this patient population and also the presence of efficacy signal described by elimination of residual disease to qualify patients for stem cell transplant.

Official Title

Chimeric Antigen Receptor T Cell Redirected to Target CD4 Positive Relapsed Refractory AML As a Bridge to Allogeneic Stem Cell Transplant

Quick Facts

Study Start:2024-03-19

Study Completion:2042-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06197672

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:12 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. ≥ 12 years old at the time of informed consent 2. Ability to provide written informed consent and HIPAA authorization. 3. Diagnosis of AML that is CD4+ and must have failed standard induction/ first line treatment such as intensive induction or less intensive hypomethylation and venetoclax first line. In the specific case of azacitidine and venetoclax (aza/ven), BM biopsy for response assessment on days 21-28 of first cycle. If disease progression by increasing number of blasts is documented, patient will be eligible. If no morphologic remission (persistent BM blasts above 5%) but evidence of efficacy exists, a second cycle without interruption will be given with the goal of achieving morphologic remission and repeat BM biopsy on days 21-28 of this cycle. If residual disease or disease progression is captured, then they will be considered refractory and will qualify for this trial. This is unless the patient now qualifies for a more intensive induction therapy that they did not qualify for when aza/ven was initially chosen as first-line treatment. Given the low response rate for aza/ven in the RR-AML, CR of only 13%, this combination would not be a prerequisite to qualify for the study. 4. If these patients who fail first line treatment have an FDA approved treatment options available (including targeted and non-targeted treatment) for a second line treatment, they do not qualify for the trial until they also are deemed nonresponsive to those. If an approved second line is not available, patients will be eligible after first line failure. 5. Creatinine clearance of \> 60ml/min (or otherwise non clinically significant, per study investigator) 6. alanine aminotransferase/ aspartate aminotransferase ALT/AST \< 3 x ULN 7. Bilirubin \< 2 x ULN (UPPER LIMIT OF NORMAL) 8. Pulmonary Function Test (PFT) with a DIFFUSE LUNG CAPACITY , DLCO, of ≥ 60% (if not completed within 6 months from Day 0) 9. Adequate echocardiogram with EJECTION FRACTION, EF, of ≥50% 10. Adequate venous access for apheresis and no other contraindications for leukapheresis 11. Confirmation of a bone marrow donor for post CD4CAR transplant to proceed to transplant if eligible post treatment.	1. CD4 negative AML 2. Pregnant or lactating women. The safety of this therapy on unborn children is not known. Female study participants of reproductive potential (see definition below) must have a negative serum or urine pregnancy test prior to initiation of conditioning chemotherapy, per research sites' clinical policy. 3. Uncontrolled active infection necessitating systemic therapy. 4. Active hepatitis B hb, or hepatitis C, HC, infection. Active hepatitis C is defined as the hepatitis C antibody is positive while quantitative HCV RNA results exceed the lower detection limit. * Subjects with a history of hepatitis B but have received antiviral therapy and have non-detectable viral DNA for 6 months prior to enrollment are eligible. * Subjects seropositive for HBS antibodies due to hepatitis B virus vaccine with no signs or active infection (Negative HBs Ag, HBc and HBe Ags) are eligible. * Subjects who had hepatitis C but have received antiviral therapy and show no detectable hepatitis C virus (HCV) viral RNA for 6 months are eligible. * If hepatitis C antibody test is positive, then patients must be tested for the presence of antigen by reverse transcription-polymerase chain reaction (RT-PCR) and be hepatitis C virus ribonucleic acid (HCV RNA) negative. 5. Concurrent use of systemic glucocorticoids in greater than replacement doses or steroid dependency defined in rheumatological and pulmonary diseases as uninterrupted corticosteroid intake for more than a year at a dosage of 0.3 mg/kg/day or greater, and where the underlying disease worsens on temporary stoppage of steroid therapy, with symptoms of steroids withdrawal (eg, lethargy, headache, weakness, pseudo rheumatism, emotional disturbances, etc) precipitated by the temporary stoppage unless tapering can occur safely without compromising the underlying disease, the withdrawal tolerance and can happen in a timeframe appropriate to enroll in this trial without safety concerns 1. Hydrocortisone 25mg/day or less 2. Prednisone 10mg/day or less 3. Dexamethasone 4mg or less Note: Recent or current use of inhaled glucocorticoids is not exclusionary, as this route pertains extremely minimal systemic penetration 6. Any previous treatment with any gene therapy products 7. Any uncontrolled active medical disorder that would preclude participation as outlined in the opinion of the treating investigator and/or Principal Investigator 8. HIV infection 9. Subjects who have received or will receive live vaccines within 30 days before the first experimental cell treatment. Inactivated seasonal flu vaccination is allowed. 10. Subjects with active autoimmune diseases who need systematic treatments (such as disease modifying agents, corticosteroids, and immunosuppressive drugs) during the last year. 11. Subjects with a history of mental disorders or drug abuse that may influence treatment compliance. 12. Active malignancy not related to AML that has required therapy in the last 3 years or is not in complete remission. Exceptions to this criterion include successfully treated non-metastatic basal cell or squamous cell skin carcinoma, or prostate cancer that does not require therapy. Other similar malignant conditions may be discussed with and permitted by the Principal Investigator 1. Specific organ function criteria for cardiac, renal, and liver function must be similar to initial inclusion values. 2. Review of co-morbidities to confirm no major changes in health status (examples of major changes include heart attack, stroke, and any major trauma) 1. Afebrile and not receiving antipyretics, and no evidence of active infection. If fever is attributed to underlying disease, it will not disqualify. 2. Specific organ function criteria for cardiac, renal, and liver function must be similar to initial inclusion values. The following tests do not need repeated: an echocardiogram if within 6 weeks of initial assessment, and the PFT if completed within 6 months from Day 0. 3. Negative pregnancy testing (if applicable) 4. If previous history of corticosteroid chemotherapy, subject must be off all but adrenal replacement doses 3 days before the CD4CAR infusion.

Inclusion Criteria

Exclusion Criteria

1. ≥ 12 years old at the time of informed consent
2. Ability to provide written informed consent and HIPAA authorization.
3. Diagnosis of AML that is CD4+ and must have failed standard induction/ first line treatment such as intensive induction or less intensive hypomethylation and venetoclax first line. In the specific case of azacitidine and venetoclax (aza/ven), BM biopsy for response assessment on days 21-28 of first cycle. If disease progression by increasing number of blasts is documented, patient will be eligible. If no morphologic remission (persistent BM blasts above 5%) but evidence of efficacy exists, a second cycle without interruption will be given with the goal of achieving morphologic remission and repeat BM biopsy on days 21-28 of this cycle. If residual disease or disease progression is captured, then they will be considered refractory and will qualify for this trial. This is unless the patient now qualifies for a more intensive induction therapy that they did not qualify for when aza/ven was initially chosen as first-line treatment. Given the low response rate for aza/ven in the RR-AML, CR of only 13%, this combination would not be a prerequisite to qualify for the study.
4. If these patients who fail first line treatment have an FDA approved treatment options available (including targeted and non-targeted treatment) for a second line treatment, they do not qualify for the trial until they also are deemed nonresponsive to those. If an approved second line is not available, patients will be eligible after first line failure.
5. Creatinine clearance of \> 60ml/min (or otherwise non clinically significant, per study investigator)
6. alanine aminotransferase/ aspartate aminotransferase ALT/AST \< 3 x ULN
7. Bilirubin \< 2 x ULN (UPPER LIMIT OF NORMAL)
8. Pulmonary Function Test (PFT) with a DIFFUSE LUNG CAPACITY , DLCO, of ≥ 60% (if not completed within 6 months from Day 0)
9. Adequate echocardiogram with EJECTION FRACTION, EF, of ≥50%
10. Adequate venous access for apheresis and no other contraindications for leukapheresis
11. Confirmation of a bone marrow donor for post CD4CAR transplant to proceed to transplant if eligible post treatment.

1. CD4 negative AML
2. Pregnant or lactating women. The safety of this therapy on unborn children is not known. Female study participants of reproductive potential (see definition below) must have a negative serum or urine pregnancy test prior to initiation of conditioning chemotherapy, per research sites' clinical policy.
3. Uncontrolled active infection necessitating systemic therapy.
4. Active hepatitis B hb, or hepatitis C, HC, infection. Active hepatitis C is defined as the hepatitis C antibody is positive while quantitative HCV RNA results exceed the lower detection limit.
* Subjects with a history of hepatitis B but have received antiviral therapy and have non-detectable viral DNA for 6 months prior to enrollment are eligible.
* Subjects seropositive for HBS antibodies due to hepatitis B virus vaccine with no signs or active infection (Negative HBs Ag, HBc and HBe Ags) are eligible.
* Subjects who had hepatitis C but have received antiviral therapy and show no detectable hepatitis C virus (HCV) viral RNA for 6 months are eligible.
* If hepatitis C antibody test is positive, then patients must be tested for the presence of antigen by reverse transcription-polymerase chain reaction (RT-PCR) and be hepatitis C virus ribonucleic acid (HCV RNA) negative.
5. Concurrent use of systemic glucocorticoids in greater than replacement doses or steroid dependency defined in rheumatological and pulmonary diseases as uninterrupted corticosteroid intake for more than a year at a dosage of 0.3 mg/kg/day or greater, and where the underlying disease worsens on temporary stoppage of steroid therapy, with symptoms of steroids withdrawal (eg, lethargy, headache, weakness, pseudo rheumatism, emotional disturbances, etc) precipitated by the temporary stoppage unless tapering can occur safely without compromising the underlying disease, the withdrawal tolerance and can happen in a timeframe appropriate to enroll in this trial without safety concerns
1. Hydrocortisone 25mg/day or less
2. Prednisone 10mg/day or less
3. Dexamethasone 4mg or less Note: Recent or current use of inhaled glucocorticoids is not exclusionary, as this route pertains extremely minimal systemic penetration
6. Any previous treatment with any gene therapy products
7. Any uncontrolled active medical disorder that would preclude participation as outlined in the opinion of the treating investigator and/or Principal Investigator
8. HIV infection
9. Subjects who have received or will receive live vaccines within 30 days before the first experimental cell treatment. Inactivated seasonal flu vaccination is allowed.
10. Subjects with active autoimmune diseases who need systematic treatments (such as disease modifying agents, corticosteroids, and immunosuppressive drugs) during the last year.
11. Subjects with a history of mental disorders or drug abuse that may influence treatment compliance.
12. Active malignancy not related to AML that has required therapy in the last 3 years or is not in complete remission. Exceptions to this criterion include successfully treated non-metastatic basal cell or squamous cell skin carcinoma, or prostate cancer that does not require therapy. Other similar malignant conditions may be discussed with and permitted by the Principal Investigator
1. Specific organ function criteria for cardiac, renal, and liver function must be similar to initial inclusion values.
2. Review of co-morbidities to confirm no major changes in health status (examples of major changes include heart attack, stroke, and any major trauma)
1. Afebrile and not receiving antipyretics, and no evidence of active infection. If fever is attributed to underlying disease, it will not disqualify.
2. Specific organ function criteria for cardiac, renal, and liver function must be similar to initial inclusion values. The following tests do not need repeated: an echocardiogram if within 6 weeks of initial assessment, and the PFT if completed within 6 months from Day 0.
3. Negative pregnancy testing (if applicable)
4. If previous history of corticosteroid chemotherapy, subject must be off all but adrenal replacement doses 3 days before the CD4CAR infusion.

Contacts and Locations

Study Contact

Tara Haney, RN

CONTACT

317-278-4184

tnhaney@iu.edu

Huda Salman, MD, PhD

CONTACT

317-278-9504

hsalman@iu.edu

Principal Investigator

Huda Salman, MD, PhD

PRINCIPAL_INVESTIGATOR

Indiana University

Study Locations (Sites)

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, 46202

United States

Collaborators and Investigators

Sponsor: Huda Salman

Huda Salman, MD, PhD, PRINCIPAL_INVESTIGATOR, Indiana University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-03-19

Study Completion Date2042-12-31

Study Record Updates

Study Start Date2024-03-19

Study Completion Date2042-12-31

Terms related to this study

Keywords Provided by Researchers

Acute Myeloid Leukemia
T Cell
Cell Therapy
CAR T
Chimeric Antigen Receptor Therapy

Additional Relevant MeSH Terms

Acute Myeloid Leukemia