RECRUITING

Chimeric Antigen Receptor T Cell Therapy Redirected to CD4 (CD4CAR)as a Second Line Treatment for Chronic Myelomonocytic Leukemia, CMML.

Conditions

Chronic Myelomonocytic Leukemia T Cell Cell Therapy CAR-T chimeric antigen

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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-directed chimeric antigen receptor engineered T-cells (CD4CAR) in patients with relapsed or refractory CMML. Specifically, the study will evaluate the safety and feasibility of CD4CAR T-cells.

Official Title

CD4CAR T Cell Therapy for CMML

Quick Facts

Study Start:2024-02-21

Study Completion:2043-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06071624

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:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. ≥ 18 years old at the time of informed consent 2. Ability to provide written informed consent and HIPAA authorization 3. Diagnosis of CMML that is CD4+ and is recurrent or refractory to first line standard of care treatment. 4. Creatinine clearance of ≥ 60 ml/min (or otherwise non clinically significant, per study investigator) 5. ALT/AST \< 3 x ULN 6. Bilirubin \< 2 x ULN 7. Pulmonary Function Test (PFT) with a DLCO of ≥ 60%. This will not have to be repeated if within 45 days of initial assessment. 8. Adequate echocardiogram with EF of ≥50% This will not have to be repeated if within 45 days of initial assessment. 9. Adequate venous access for apheresis and no other contraindications for leukapheresis	1. CD4 negative CMML 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 or hepatitis C 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 Note: Replacement therapy (thyroxine, insulin or physiological corticosteroid replacement therapy (up to10 mg of oral daily prednisone or equivalent in hydrocortisone and dexamethasone) to treat adrenal dysfunction or pituitary dysfunction) is not considered as systematic therapy. Subjects who need inhalation corticosteroid therapy can be included in this trial. Subjects with vitiligo or in long-term remission of pediatric asthma or allergic diseases can be included in this trial 11. Subjects with a history of mental disorders or drug abuse that may influence treatment compliance 12. Active malignancy not related to CMML 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. 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. Tests such as echocardiogram and PFTs need not be repeated if within 45 days of initial assessment 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 5. Planned infusion dose was successfully manufactured and met release criteria

Inclusion Criteria

Exclusion Criteria

1. ≥ 18 years old at the time of informed consent
2. Ability to provide written informed consent and HIPAA authorization
3. Diagnosis of CMML that is CD4+ and is recurrent or refractory to first line standard of care treatment.
4. Creatinine clearance of ≥ 60 ml/min (or otherwise non clinically significant, per study investigator)
5. ALT/AST \< 3 x ULN
6. Bilirubin \< 2 x ULN
7. Pulmonary Function Test (PFT) with a DLCO of ≥ 60%. This will not have to be repeated if within 45 days of initial assessment.
8. Adequate echocardiogram with EF of ≥50% This will not have to be repeated if within 45 days of initial assessment.
9. Adequate venous access for apheresis and no other contraindications for leukapheresis

1. CD4 negative CMML
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 or hepatitis C 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 Note: Replacement therapy (thyroxine, insulin or physiological corticosteroid replacement therapy (up to10 mg of oral daily prednisone or equivalent in hydrocortisone and dexamethasone) to treat adrenal dysfunction or pituitary dysfunction) is not considered as systematic therapy. Subjects who need inhalation corticosteroid therapy can be included in this trial. Subjects with vitiligo or in long-term remission of pediatric asthma or allergic diseases can be included in this trial
11. Subjects with a history of mental disorders or drug abuse that may influence treatment compliance
12. Active malignancy not related to CMML 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. 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. Tests such as echocardiogram and PFTs need not be repeated if within 45 days of initial assessment
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
5. Planned infusion dose was successfully manufactured and met release criteria

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 Date2024-02-21

Study Completion Date2043-12

Study Record Updates

Study Start Date2024-02-21

Study Completion Date2043-12

Terms related to this study

Keywords Provided by Researchers

Chronic Myelomonocytic Leukemia
T Cell
Cell Therapy
CAR-T
chimeric antigen

Additional Relevant MeSH Terms

Chronic Myelomonocytic Leukemia