RECRUITING

Phase I/II Study of Engineered T Cell Receptor-Modified NK Cells Targeting PRAME in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapse/Refractory Myeloid Malignancies

Conditions

Lymphodepleting Chemotherapy Myeloid Malignancies

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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

To find a recommended dose of PRAME-TCR-NK cells that can be given to patients with AML or MDS.

Official Title

Phase I/II Study of Engineered T Cell Receptor-Modified NK Cells Targeting PRAME in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapse/Refractory Myeloid Malignancies

Quick Facts

Study Start:2024-06-26

Study Completion:2029-04-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06383572

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 to 75 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. 18-75 years of age. English and non-English speaking participants are eligible 2. Participants with one of the following hematological malignances: AML, MDS/CMML, Multiple myeloma 3. Participants must meet disease specific eligibility criteria (see below) 4. Participants at least 3 weeks from last cytotoxic chemotherapy at the time of starting lymphodepleting chemotherapy, except for Hydroxyurea which is allowed for peripheral blood count control in AML patients until the day prior to administration of lymphodepleting chemotherapy. Patients may continue tyrosine kinase inhibitors or other targeted therapies until up to three days prior to administration of lymphodepleting chemotherapy. 5. Localized radiotherapy to one or more disease sites is allowed prior the infusion provided that there are additional disease sites that are not irradiated to assess response 6. Karnofsky Performance Scale \> 50%. 7. Adequate organ function:as described in 7-10 8. Renal: Serum creatinine \</= 2.0 mg/dL and estimated Glomerular Filtration Rate (eGFR using the CKD-EPI equation).GFR = 141 x \[min(Scr/k), 1)a x max (Scr/k), 1) -1.209\] x Age-0.993 x 1.018 \[if female\] x \[ 1.157 if Black\] (a is 0.329 for females and 0.411 for males; min indicates minimum of Scr/k or 1, and max indicates maximum of Scr/k or 1) 9. Hepatic: ALT/AST \</= 2.5 x ULN or \</= 5 x ULN if documented liver metastases, Total bilirubin \</= 1.5 mg/dL, except in subjects with Gilbert's Syndrome in whom total bilirubin must be \</= 3.0 mg/dL. No history of liver cirrhosis. No ascites. 10. Cardiac: Cardiac ejection fraction \>/= 40%, no clinically significant pericardial effusion as determined by an ECHO, and no uncontrolled arrhythmias or symptomatic cardiac disease. 11. Pulmonary: No clinically significant pleural effusion (per PI discretion), baseline oxygen saturation \> 92% on room air and adequate pulmonary function with FEV1, FVC and DLCO (corrected for Hgb) \>50%. 12. Able to provide written informed consent. 13. All participants who are able to have children must practice effective birth control while on study and up to 3 months post completion of study therapy. Acceptable forms of birth control for female patients include: hormonal birth control, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence, for the length of the study. If the participant is a female and becomes pregnant or suspects pregnancy, she must immediately notify her doctor. If the participant becomes pregnant during this study, she will be taken off this study. 14. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of study agent administration. Men who are able to have children must use effective birth control while on the study. If the male participant fathers a child or suspects that he has fathered a child while on the study, he must immediately notify his doctor. 15. Signed consent to long-term follow-up protocol PA17-0483 to fulfill the institutional responsibilities to various regulatory agencies. 16. Life Expectancy \>=3 mo, by PI assessment 17. Participants are HLA-A\*02:01 positive on HLA typing 17. Participants must have one of the following diseases: 1. Greater than 1 cycle of induction therapy required to achieve morphologic remission (must still have MRD detectable) 2. Treatment-related AML 3. Primary induction failure 4. Have minimal residual disease by morphology, flow cytometry, FISH, detection of disease related mutations or cytogenetic abnormality after first course of induction chemotherapy 5. Have relapsed after prior allogeneic hematopoietic transplant	1. Positive beta HCG in female of child-bearing potential defined as not postmenopausal for 24 months or no previous surgical sterilization or lactating females. 2. Presence of clinically significant Grade 3 or greater toxicity from the previous treatment, as determined by PI. 3. Presence of uncontrolled fungal, bacterial, viral, or other infection not responding to appropriate therapy. 4. Known active hepatitis B or C. 5. Known HIV with detectable viral load 6. Presence of active neurological disorder(s). 7. Active autoimmune disease within 12 months of enrollment 8. Active cerebral or meningeal involvement by the malignancy 9. Active (defined as requiring therapy) acute or chronic GVHD 10. Any other malignancy known to be active, except for treated cervical intra-epithelial neoplasia and non-melanoma skin cancer. 11. Presence of any other serious medical condition that may endanger the patient at investigator discretion. 12. Major surgery \<4 weeks prior to first dose of the preparatory chemotherapy 13. Allogeneic SCT or DLI \<12 weeks prior to first dose of preparatory chemotherapy 14. Concomitant use of other investigational agents. 15. Concomitant use of other anti-cancer agents. 16. Participants receiving systemic steroid therapy at time of enrollment (physiological substitutive doses are allowed), or have received antithymocyte globulin or lymphocyte immune globulin within 14 days of enrollment or alemtuzumab within 28 days of enrollment. 17. Participants receiving immunosuppressive therapy

Inclusion Criteria

Exclusion Criteria

1. 18-75 years of age. English and non-English speaking participants are eligible
2. Participants with one of the following hematological malignances: AML, MDS/CMML, Multiple myeloma
3. Participants must meet disease specific eligibility criteria (see below)
4. Participants at least 3 weeks from last cytotoxic chemotherapy at the time of starting lymphodepleting chemotherapy, except for Hydroxyurea which is allowed for peripheral blood count control in AML patients until the day prior to administration of lymphodepleting chemotherapy. Patients may continue tyrosine kinase inhibitors or other targeted therapies until up to three days prior to administration of lymphodepleting chemotherapy.
5. Localized radiotherapy to one or more disease sites is allowed prior the infusion provided that there are additional disease sites that are not irradiated to assess response
6. Karnofsky Performance Scale \> 50%.
7. Adequate organ function:as described in 7-10
8. Renal: Serum creatinine \</= 2.0 mg/dL and estimated Glomerular Filtration Rate (eGFR using the CKD-EPI equation).GFR = 141 x \[min(Scr/k), 1)a x max (Scr/k), 1) -1.209\] x Age-0.993 x 1.018 \[if female\] x \[ 1.157 if Black\] (a is 0.329 for females and 0.411 for males; min indicates minimum of Scr/k or 1, and max indicates maximum of Scr/k or 1)
9. Hepatic: ALT/AST \</= 2.5 x ULN or \</= 5 x ULN if documented liver metastases, Total bilirubin \</= 1.5 mg/dL, except in subjects with Gilbert's Syndrome in whom total bilirubin must be \</= 3.0 mg/dL. No history of liver cirrhosis. No ascites.
10. Cardiac: Cardiac ejection fraction \>/= 40%, no clinically significant pericardial effusion as determined by an ECHO, and no uncontrolled arrhythmias or symptomatic cardiac disease.
11. Pulmonary: No clinically significant pleural effusion (per PI discretion), baseline oxygen saturation \> 92% on room air and adequate pulmonary function with FEV1, FVC and DLCO (corrected for Hgb) \>50%.
12. Able to provide written informed consent.
13. All participants who are able to have children must practice effective birth control while on study and up to 3 months post completion of study therapy. Acceptable forms of birth control for female patients include: hormonal birth control, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence, for the length of the study. If the participant is a female and becomes pregnant or suspects pregnancy, she must immediately notify her doctor. If the participant becomes pregnant during this study, she will be taken off this study.
14. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of study agent administration. Men who are able to have children must use effective birth control while on the study. If the male participant fathers a child or suspects that he has fathered a child while on the study, he must immediately notify his doctor.
15. Signed consent to long-term follow-up protocol PA17-0483 to fulfill the institutional responsibilities to various regulatory agencies.
16. Life Expectancy \>=3 mo, by PI assessment
17. Participants are HLA-A\*02:01 positive on HLA typing
17. Participants must have one of the following diseases:
1. Greater than 1 cycle of induction therapy required to achieve morphologic remission (must still have MRD detectable)
2. Treatment-related AML
3. Primary induction failure
4. Have minimal residual disease by morphology, flow cytometry, FISH, detection of disease related mutations or cytogenetic abnormality after first course of induction chemotherapy
5. Have relapsed after prior allogeneic hematopoietic transplant

1. Positive beta HCG in female of child-bearing potential defined as not postmenopausal for 24 months or no previous surgical sterilization or lactating females.
2. Presence of clinically significant Grade 3 or greater toxicity from the previous treatment, as determined by PI.
3. Presence of uncontrolled fungal, bacterial, viral, or other infection not responding to appropriate therapy.
4. Known active hepatitis B or C.
5. Known HIV with detectable viral load
6. Presence of active neurological disorder(s).
7. Active autoimmune disease within 12 months of enrollment
8. Active cerebral or meningeal involvement by the malignancy
9. Active (defined as requiring therapy) acute or chronic GVHD
10. Any other malignancy known to be active, except for treated cervical intra-epithelial neoplasia and non-melanoma skin cancer.
11. Presence of any other serious medical condition that may endanger the patient at investigator discretion.
12. Major surgery \<4 weeks prior to first dose of the preparatory chemotherapy
13. Allogeneic SCT or DLI \<12 weeks prior to first dose of preparatory chemotherapy
14. Concomitant use of other investigational agents.
15. Concomitant use of other anti-cancer agents.
16. Participants receiving systemic steroid therapy at time of enrollment (physiological substitutive doses are allowed), or have received antithymocyte globulin or lymphocyte immune globulin within 14 days of enrollment or alemtuzumab within 28 days of enrollment.
17. Participants receiving immunosuppressive therapy

Contacts and Locations

Study Contact

Jeremy Ramdial, MD

CONTACT

(713) 745-0146

jlramdial@mdanderson.org

Principal Investigator

Jeremy Ramdial, MD

PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Study Locations (Sites)

MD Anderson Cancer Center

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: M.D. Anderson Cancer Center

Jeremy Ramdial, MD, PRINCIPAL_INVESTIGATOR, M.D. Anderson Cancer Center

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 Date2024-06-26

Study Completion Date2029-04-01

Study Record Updates

Study Start Date2024-06-26

Study Completion Date2029-04-01

Terms related to this study

Additional Relevant MeSH Terms

Lymphodepleting Chemotherapy
Myeloid Malignancies