RECRUITING

PLAT-08: a Study of SC-DARIC33 CAR T Cells in Pediatric and Young Adults with Relapsed or Refractory CD33+ AML

Conditions

Acute Myeloid Leukemia Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia, in Relapse

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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

A phase 1, open-label, non-randomized study enrolling pediatric and young adult patients with relapsed or refractory CD33+ leukemia with and without prior history of allogeneic hematopoietic cell transplantation, to examine the safety and feasibility of administering an autologous T cell product that has been genetically modified to express a Dimerizing Agent Regulated Immunoreceptor Complex (DARIC).

Official Title

Pediatric and Young Adult Leukemia Adoptive Therapy (PLAT)-08: a Phase 1 Study of SC-DARIC33 in Pediatric and Young Adults with Relapsed or Refractory CD33+ AML

Quick Facts

Study Start:2021-11-29

Study Completion:2041-01-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05105152

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:Not specified to 30 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
1. Subject age ≤ 30 years. The first three enrolled subjects must be ≥ 18 years of age. 2. AML that expresses CD33 by flow cytometry and meets one of the below definitions: 1. For subjects who have previously received an allogeneic HCT, any evidence of AML re-emergence post HCT detectable by flow cytometry 2. First relapse of AML ≤ 6 months of initial diagnosis 3. First relapse of AML \> 6 months after initial diagnosis, with MRD of \>0.1% by flow cytometry (MPF) after at least one re-induction (single cycle) attempt 4. Second or greater relapse AML 5. Refractory AML, defined as \>1% leukemic cells determined by flow cytometry after 2 cycles of induction chemotherapy 3. Able to tolerate apheresis, or subject with sufficient existing apheresis product or T cells for manufacturing investigational product. 4. Life expectancy ≥ 8 weeks 5. Has an appropriate stem cell donor source identified 6. Lansky performance status score of ≥ 50 for subjects \<16 years of age or Karnofsky score ≥ 50 for subjects ≥ 16 years. Subjects who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for purposes of assessing performance status 7. If a subject does not have a previously obtained apheresis product that is acceptable and available for manufacturing of DARIC T cells, the subject must discontinue all anticancer agents and radiotherapy and, in the opinion of the investigator, have fully recovered from significant acute toxic effects of all prior chemotherapy, immunotherapy, and radiotherapy: 8. Adequate organ function as indicated by: 1. Renal: Serum creatinine ≤ 1.5 X the upper limit of normal (ULN) 2. Hepatic: Total bilirubin ≤ 3 times ULN for age OR conjugated bilirubin ≤ 2 mg/dL AND ALT (SGPT) ≤ 5 times ULN 3. Cardiac: Shortening fraction ≥ 28% OR ejection fraction ≥ 50% as measured by echocardiogram 4. Respiratory: Oxygen saturation ≥ 92% on room air without supplemental oxygen or mechanical ventilation 9. Laboratory values meet the following criteria: 10. If subject is of childbearing or child-fathering potential, must agree to use highly effective contraception from the time of initial consent through 12 months following the infusion of investigational product on this trial. 11. Subject and/or legally authorized representative has signed the Informed Consent Form for this study	1. Active malignancy other than acute myeloid leukemia 2. History of symptomatic non-AML CNS disease or ongoing symptomatic CNS disease requiring medical intervention, including paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injury, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination or movement disorder (subjects with non-febrile seizure disorder controlled on anti-epileptic medication and without seizure activity within 1 month are eligible). 3. CNS AML involvement that is symptomatic and in the opinion of the investigator, cannot be controlled during the interval between enrollment and DARIC T cell infusion 4. If history of allogeneic stem cell transplant: active GVHD, or receiving immunosuppressive therapy for treatment or prevention of GVHD within 4 weeks prior to enrollment 5. Presence of active severe infection, defined as: 6. Primary immunodeficiency syndrome 7. Subject has received prior virotherapy 8. Pregnant or breastfeeding 9. Subject and/or legally authorized representative unwilling to provide consent/assent for participation in the 15-year follow-up period, required if DARIC T cell therapy is administered 10. Presence of any condition that, in the opinion of the investigator, would prohibit the subject from undergoing treatment under this protocol 11. Considered by the investigator to be unable to tolerate a lymphodepleting regimen 12. Subject has a contraindication to receiving rapamycin

Inclusion Criteria

Exclusion Criteria

1. Subject age ≤ 30 years. The first three enrolled subjects must be ≥ 18 years of age.
2. AML that expresses CD33 by flow cytometry and meets one of the below definitions:
1. For subjects who have previously received an allogeneic HCT, any evidence of AML re-emergence post HCT detectable by flow cytometry
2. First relapse of AML ≤ 6 months of initial diagnosis
3. First relapse of AML \> 6 months after initial diagnosis, with MRD of \>0.1% by flow cytometry (MPF) after at least one re-induction (single cycle) attempt
4. Second or greater relapse AML
5. Refractory AML, defined as \>1% leukemic cells determined by flow cytometry after 2 cycles of induction chemotherapy
3. Able to tolerate apheresis, or subject with sufficient existing apheresis product or T cells for manufacturing investigational product.
4. Life expectancy ≥ 8 weeks
5. Has an appropriate stem cell donor source identified
6. Lansky performance status score of ≥ 50 for subjects \<16 years of age or Karnofsky score ≥ 50 for subjects ≥ 16 years. Subjects who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for purposes of assessing performance status
7. If a subject does not have a previously obtained apheresis product that is acceptable and available for manufacturing of DARIC T cells, the subject must discontinue all anticancer agents and radiotherapy and, in the opinion of the investigator, have fully recovered from significant acute toxic effects of all prior chemotherapy, immunotherapy, and radiotherapy:
8. Adequate organ function as indicated by:
1. Renal: Serum creatinine ≤ 1.5 X the upper limit of normal (ULN)
2. Hepatic: Total bilirubin ≤ 3 times ULN for age OR conjugated bilirubin ≤ 2 mg/dL AND ALT (SGPT) ≤ 5 times ULN
3. Cardiac: Shortening fraction ≥ 28% OR ejection fraction ≥ 50% as measured by echocardiogram
4. Respiratory: Oxygen saturation ≥ 92% on room air without supplemental oxygen or mechanical ventilation
9. Laboratory values meet the following criteria:
10. If subject is of childbearing or child-fathering potential, must agree to use highly effective contraception from the time of initial consent through 12 months following the infusion of investigational product on this trial.
11. Subject and/or legally authorized representative has signed the Informed Consent Form for this study

1. Active malignancy other than acute myeloid leukemia
2. History of symptomatic non-AML CNS disease or ongoing symptomatic CNS disease requiring medical intervention, including paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injury, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination or movement disorder (subjects with non-febrile seizure disorder controlled on anti-epileptic medication and without seizure activity within 1 month are eligible).
3. CNS AML involvement that is symptomatic and in the opinion of the investigator, cannot be controlled during the interval between enrollment and DARIC T cell infusion
4. If history of allogeneic stem cell transplant: active GVHD, or receiving immunosuppressive therapy for treatment or prevention of GVHD within 4 weeks prior to enrollment
5. Presence of active severe infection, defined as:
6. Primary immunodeficiency syndrome
7. Subject has received prior virotherapy
8. Pregnant or breastfeeding
9. Subject and/or legally authorized representative unwilling to provide consent/assent for participation in the 15-year follow-up period, required if DARIC T cell therapy is administered
10. Presence of any condition that, in the opinion of the investigator, would prohibit the subject from undergoing treatment under this protocol
11. Considered by the investigator to be unable to tolerate a lymphodepleting regimen
12. Subject has a contraindication to receiving rapamycin

Contacts and Locations

Study Contact

Adam Lamble, MD

CONTACT

206-986-2106

CBDCIntake@seattlechildrens.org

Study Locations (Sites)

Seattle Children's Hospital

Seattle, Washington, 98105

United States

Collaborators and Investigators

Sponsor: Seattle Children's Hospital

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 Date2021-11-29

Study Completion Date2041-01-31

Study Record Updates

Study Start Date2021-11-29

Study Completion Date2041-01-31

Terms related to this study

Additional Relevant MeSH Terms

Acute Myeloid Leukemia
Acute Myeloid Leukemia Refractory
Acute Myeloid Leukemia, in Relapse