search
Back to results

PLAT-08: A Study Of SC-DARIC33 CAR T Cells In Pediatric And Young Adults With Relapsed Or Refractory CD33+ AML

Primary Purpose

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

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
SC-DARIC33
Sponsored by
Seattle Children's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia

Eligibility Criteria

undefined - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion 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:

    a. Chemotherapy and biologic agents: All chemotherapy and biologic therapy not specifically mentioned below must be discontinued ≥ 7 days prior to enrollment, with the exception of intrathecal chemotherapy for which there is not a required washout period b. Must be ≥ 30 days from last gemtuzumab ozogamicin dose. c. Steroid use: All corticosteroid therapy (unless physiologic replacement dosing) must be discontinued ≥ 7 days prior to enrollment d. Tyrosine Kinase Inhibitor (TKI) use: All TKIs must be discontinued ≥ 3 days prior to enrollment e. Hydroxyurea: must be discontinued ≥ 1 day prior to enrollment. f. Gene Modified cellular therapy: i. must be at least 30 days from most recent gene modified cell therapy infusion and document no evidence of modified cells in the peripheral blood OR ii. must be at least 60 days from most recent gene modified cell therapy

  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:

    a. Subjects requiring apheresis: Absolute Lymphocyte Count (ALC) ≥ 100 cells/uL b. Virology Testing negative within 3 months prior to enrollment, to include: i. HIV antigen & antibody ii. Hepatitis B surface antigen iii. Hepatitis C antibody OR if positive, Hepatitis C PCR is negative

  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

Exclusion Criteria:

  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:

    i. positive blood culture within 48 hours of enrollment, OR ii. fever above 38.2° C, AND clinical signs of infection within 48 hours of enrollment

  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

Sites / Locations

  • Seattle Children's HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

DARIC-33

Arm Description

Outcomes

Primary Outcome Measures

Adverse events associated with SC-DARIC33 cell product infusions will be assessed
The type, frequency, severity, and duration of adverse events will be summarized
Ability to successfully manufacture SC-DARIC33
Measure of the number of successfully manufactured SC-DARIC33 products

Secondary Outcome Measures

Acute Myeloid Leukemia response to SC-DARIC in subjects with relapsed or refractory CD33+ myeloid leukemia will be assessed
The efficacy of the SC-DARIC33 assessed based on the bone marrow aspirate testing following SC-DARIC infusion

Full Information

First Posted
October 7, 2021
Last Updated
June 27, 2023
Sponsor
Seattle Children's Hospital
Collaborators
2seventy bio
search

1. Study Identification

Unique Protocol Identification Number
NCT05105152
Brief Title
PLAT-08: A Study Of SC-DARIC33 CAR T Cells In Pediatric And Young Adults With Relapsed Or Refractory CD33+ AML
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 29, 2021 (Actual)
Primary Completion Date
February 29, 2024 (Anticipated)
Study Completion Date
January 31, 2039 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Seattle Children's Hospital
Collaborators
2seventy bio

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Acute Myeloid Leukemia Refractory, Acute Myeloid Leukemia, in Relapse

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Phase I open-label, dose-finding study employing the Bayesian optimal interval (BOIN) design
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
DARIC-33
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
SC-DARIC33
Intervention Description
Infusion with SC-DARIC33 followed by intermittent oral rapamycin administration
Primary Outcome Measure Information:
Title
Adverse events associated with SC-DARIC33 cell product infusions will be assessed
Description
The type, frequency, severity, and duration of adverse events will be summarized
Time Frame
28 days post-infusion
Title
Ability to successfully manufacture SC-DARIC33
Description
Measure of the number of successfully manufactured SC-DARIC33 products
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Acute Myeloid Leukemia response to SC-DARIC in subjects with relapsed or refractory CD33+ myeloid leukemia will be assessed
Description
The efficacy of the SC-DARIC33 assessed based on the bone marrow aspirate testing following SC-DARIC infusion
Time Frame
28 days post-infusion

10. Eligibility

Sex
All
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subject age ≤ 30 years. The first three enrolled subjects must be ≥ 18 years of age. AML that expresses CD33 by flow cytometry and meets one of the below definitions: For subjects who have previously received an allogeneic HCT, any evidence of AML re-emergence post HCT detectable by flow cytometry First relapse of AML ≤ 6 months of initial diagnosis 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 Second or greater relapse AML Refractory AML, defined as >1% leukemic cells determined by flow cytometry after 2 cycles of induction chemotherapy Able to tolerate apheresis, or subject with sufficient existing apheresis product or T cells for manufacturing investigational product. Life expectancy ≥ 8 weeks Has an appropriate stem cell donor source identified 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 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: a. Chemotherapy and biologic agents: All chemotherapy and biologic therapy not specifically mentioned below must be discontinued ≥ 7 days prior to enrollment, with the exception of intrathecal chemotherapy for which there is not a required washout period b. Must be ≥ 30 days from last gemtuzumab ozogamicin dose. c. Steroid use: All corticosteroid therapy (unless physiologic replacement dosing) must be discontinued ≥ 7 days prior to enrollment d. Tyrosine Kinase Inhibitor (TKI) use: All TKIs must be discontinued ≥ 3 days prior to enrollment e. Hydroxyurea: must be discontinued ≥ 1 day prior to enrollment. f. Gene Modified cellular therapy: i. must be at least 30 days from most recent gene modified cell therapy infusion and document no evidence of modified cells in the peripheral blood OR ii. must be at least 60 days from most recent gene modified cell therapy Adequate organ function as indicated by: Renal: Serum creatinine ≤ 1.5 X the upper limit of normal (ULN) Hepatic: Total bilirubin ≤ 3 times ULN for age OR conjugated bilirubin ≤ 2 mg/dL AND ALT (SGPT) ≤ 5 times ULN Cardiac: Shortening fraction ≥ 28% OR ejection fraction ≥ 50% as measured by echocardiogram Respiratory: Oxygen saturation ≥ 92% on room air without supplemental oxygen or mechanical ventilation Laboratory values meet the following criteria: a. Subjects requiring apheresis: Absolute Lymphocyte Count (ALC) ≥ 100 cells/uL b. Virology Testing negative within 3 months prior to enrollment, to include: i. HIV antigen & antibody ii. Hepatitis B surface antigen iii. Hepatitis C antibody OR if positive, Hepatitis C PCR is negative 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. Subject and/or legally authorized representative has signed the Informed Consent Form for this study Exclusion Criteria: Active malignancy other than acute myeloid leukemia 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). 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 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 Presence of active severe infection, defined as: i. positive blood culture within 48 hours of enrollment, OR ii. fever above 38.2° C, AND clinical signs of infection within 48 hours of enrollment Primary immunodeficiency syndrome Subject has received prior virotherapy Pregnant or breastfeeding 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 Presence of any condition that, in the opinion of the investigator, would prohibit the subject from undergoing treatment under this protocol Considered by the investigator to be unable to tolerate a lymphodepleting regimen Subject has a contraindication to receiving rapamycin
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Adam Lamble, MD
Phone
206-986-2106
Email
CBDCIntake@seattlechildrens.org
Facility Information:
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Adam Lamble, MD
Email
CBDCIntake@seattlechildrens.org
First Name & Middle Initial & Last Name & Degree
Adam Lamble, MD

12. IPD Sharing Statement

Learn more about this trial

PLAT-08: A Study Of SC-DARIC33 CAR T Cells In Pediatric And Young Adults With Relapsed Or Refractory CD33+ AML

We'll reach out to this number within 24 hrs