Study Stopped
Administrative decision
CART-38 in Adult AML and MM Patients
Phase 1 Study of Lintivirally Transduced T Cells Engineered to Contain Anti-CD38 Linked to TCRζ and 4-1BB Signaling Domains in Subjects With Acute Myeloid Leukemia and Multiple Myeloma
1 other identifier
interventional
11
1 country
1
Brief Summary
This is an open-label Phase 1 study to estimate the safety and manufacturing feasibility of lentivirally transduced T cells expressing anti-CD38 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ /4-1BB) costimulatory domains in patients with Acute Myeloid Leukemia and Multiple Myeloma. This CAR T cell product will be referred to as "CART-38 cells".
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started May 2023
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 28, 2022
CompletedFirst Posted
Study publicly available on registry
July 5, 2022
CompletedStudy Start
First participant enrolled
May 30, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 9, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
February 9, 2025
CompletedJune 26, 2025
June 1, 2025
1.7 years
June 28, 2022
June 24, 2025
Conditions
Outcome Measures
Primary Outcomes (3)
Number of Subjects with treatment related adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE) V5.0
15 years
Number of subjects with dose-limiting toxicities
12 months
Determination of maximum tolerated dose assessed by collection of adverse events as graded by CTCAE.
12 months
Secondary Outcomes (9)
Proportion of subjects who enroll on the study who receive study treatment
12 months
Proportion of product release failures
12 months
Frequency of manufacturing failures as determined by production of study treatment that meets protocol defined targeted dose
12 months
Overall Response Rate (ORR)
12 months
Overall Survival (OS)
15 years
- +4 more secondary outcomes
Study Arms (8)
Cohort A Dose Level 1: Relapsed/Refractory Acute Myeloid Leukemia (AML)
EXPERIMENTALCohort A Dose Level 1: Adult patients ages ≥ 18 with acute myeloid leukemia (AML) who have not achieved remission after at least two lines of prior therapy will receive a single fixed dose of 3x10(6) CART 38 Cells via intravenous infusion on Day 0, following lymphodepleting chemotherapy with cyclophosphamide or fludarabine based on physician discretion.
Cohort A Dose Level -1 :Relapsed/Refractory Acute Myeloid Leukemia (AML)
EXPERIMENTALCohort A Dose Level -1: Adult patients ages ≥ 18 with acute myeloid leukemia (AML) will receive a single fixed dose of 7x10(5) CART 38 Cells via intravenous infusion on Day 0, following lymphodepleting chemotherapy with cyclophosphamide or fludarabine based on physician discretion.
Cohort A Dose Level 2 :Relapsed/Refractory Acute Myeloid Leukemia (AML)
EXPERIMENTALCohort A Dose Level 2: Adult patients ages ≥ 18 with acute myeloid leukemia (AML) will receive a single fixed dose of 7x10(6) CART 38 Cells via intravenous infusion on Day 0, following lymphodepleting chemotherapy with cyclophosphamide or fludarabine based on physician discretion.
Cohort A Dose Level 3 :Relapsed/Refractory Acute Myeloid Leukemia (AML)
EXPERIMENTALCohort A Dose Level 3: Adult patients ages ≥ 18 with acute myeloid leukemia (AML) will receive a single fixed dose of 3x10(7) CART 38 Cells via intravenous infusion on Day 0, following lymphodepleting chemotherapy with cyclophosphamide or fludarabine based on physician discretion.
Cohort B Dose Level 1: Multiple Myeloma (MM)
EXPERIMENTALCohort B Dose Level 1 - Adult patients ages ≥ 18 with Multiple Myeloma (MM) who have not achieved remission after at least two lines of prior therapy will receive a single fixed dose of 3x10(6) CART 38 Cells via intravenous infusion on Day 0, following lymphodepleting chemotherapy with cyclophosphamide or fludarabine based on physician discretion.
Cohort B Dose Level -1: Multiple Myeloma (MM)
EXPERIMENTALCohort B Dose Level -1 - Adult patients ages ≥ 18 with Multiple Myeloma (MM) who have not achieved remission after at least two lines of prior therapy will receive a single fixed dose of 7x10(5) CART 38 Cells via intravenous infusion on Day 0, following lymphodepleting chemotherapy with cyclophosphamide or fludarabine based on physician discretion.
Cohort B Dose Level 2: Multiple Myeloma (MM)
EXPERIMENTALCohort B Dose Level 2 - Adult patients ages ≥ 18 with Multiple Myeloma (MM) who have not achieved remission after at least two lines of prior therapy will receive a single fixed dose of 7x10(6) CART 38 Cells via intravenous infusion on Day 0, following lymphodepleting chemotherapy with cyclophosphamide or fludarabine based on physician discretion.
Cohort B Dose Level 3: Multiple Myeloma (MM)
EXPERIMENTALCohort B Dose Level 3 - Adult patients ages ≥ 18 with Multiple Myeloma (MM) who have not achieved remission after at least two lines of prior therapy will receive a single fixed dose of 3x10(7) CART 38 Cells via intravenous infusion on Day 0, following lymphodepleting chemotherapy with cyclophosphamide or fludarabine based on physician discretion.
Interventions
3x10(6) CART-38 cells via intravenous infusion
7x10(5) CART-38 cells via intravenous infusion
7x10(6) CART-38 cells via intravenous infusion
3x10(7) CART-38 cells via intravenous infusion
Lymphodepleting chemotherapy administered at physician discretion
Lymphodepleting chemotherapy administered at physician discretion
Eligibility Criteria
You may qualify if:
- Male or female patients age ≥ 18 years.
- Patients must have one of the following diagnoses:
- a. Cohort A: Acute Myeloid Leukemia (AML) which meets one of the following criteria: i. Patients with second or greater relapse defined as flow cytometric confirmation of myeloid leukemia of at least 0.1% after second documented complete remission; OR ii. Patients with detectable disease post-allogeneic transplant with flow cytometric confirmation (MRD) of myeloid leukemia of at least 0.1%; OR iii. Patients with refractory disease defined as persistent bone marrow involvement with \>5% blasts after two courses of induction chemotherapy for patients at initial presentation or \>5% bone marrow blasts after one course of re-induction chemotherapy for patients who have relapsed after previously achieving a complete remission; OR iv. Patients with relapsed disease (defined as \>5% bone marrow blasts after one course of standard chemotherapy) after previously achieving a complete remission. Note: Two cycles of combination therapy with a hypomethylating agent and venetoclax is considered one course of standard AML chemotherapy for the purpose of this criteria.
- b. Cohort B: Relapsed/refractory multiple myeloma (MM) according to IMWG 2016 criteria which meets the following conditions: i. Relapsed/refractory disease after receiving ≥ 3 lines of therapy, to ensure the patient has been exposed to ≥ 1 IMiD®, ≥ 1 proteasome inhibitor, and daratumumab; where refractory MM is defined as the achievement of less than a partial response (\< PR after ≥ 2 cycles) and relapsed MM requires patients be ≤ 12 months from the last dose of their prior treatment regimen to confirmation of relapse) AND ii. Patients must also have measurable disease as defined by one of the following:
- \. Serum M-protein ≥ 0.5 g/dL; 2. Urine M-protein ≥ 200 mg/24 hours; 3. Serum free light chain (FLC) assay; involved FLC level ≥ 100 mg/L provided the serum FLC ratio is abnormal; 4. ≥ 30% clonal plasma cells in the bone marrow aspirate or biopsy sample; 5. Measurable plasmacytomas \> 2 cm in cross sectional diameter.
- \. AML only: Documentation of CD38 Expression on leukemic blasts by flow or by immunohistochemistry (IHC). Results must be confirmed after last documented relapse and after any CD38-directed therapy (if applicable).
- \. Confirmed availability of cells for a rescue transplant as a therapeutic back-up option as follows:
- Cohort A (AML): Patients must have a suitable stem cell donor available who may donate cells in the event the subject needs to undergo an allogeneic HSCT. Donor may be matched or mismatched and must be found to be suitable according to the institution's standard criteria; donors must be fully cleared to proceed as the donor.
- Cohort B (MM): Previously harvested autologous stem cells \> 2x106/kg CD34+ cells.
- \. Adequate organ function defined as:
- a. Creatinine ≤ 2.5 mg/dl or Creatinine Clearance \> 30ml/min b. ALT/AST ≤ 5x upper limit of normal range c. Direct bilirubin ≤ 2.0 mg/dl, unless the subject has Gilbert's syndrome (≤3.0 mg/dl) d. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen \> 92% on room air e. Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA
- \. ECOG Performance Status that is either 0 or 1. 7. Signed informed consent form 8. Subjects of reproductive potential must agree to use acceptable birth control methods.
You may not qualify if:
- Evidence of active hepatitis B or active hepatitis C. The following would not qualify as an active infection, thus would not exclude the subject from participating:
- Positive HBV serology with undetectable viral load and ongoing antiviral prophylaxis for potential HBV reactivation.
- Positive HCV serology with quantitative PCR for plasma HCV RNA below the lower limit of detection, with or without concurrent antiviral HCV treatment
- Any active, uncontrolled infection
- Severe, active co-morbidity that in the opinion of the physician-investigator would preclude participation in this study.
- Class III/IV cardiovascular disability according to the New York Heart Association Classification
- Patients with known somatic JAK2 V617F mutation by PCR or next generation sequencing.
- Patients \< 3 months from prior autologous transplant or \< 6 months from prior allo ASCT .
- Active acute or chronic GVHD requiring systemic therapy.
- Dependence on systemic steroids or immunosuppressant medications.
- Active CNS disease. patients with a history of CNS involvement that was successfully treated are eligible. Additional CNS testing such as a lumbar puncture and/or brain imaging is only required for eligibility if a subject is experiencing signs/symptoms of CNS involvement.
- Pregnant or nursing (lactating) women.
- Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, and unrelated to their cancer or previous cancer treatment.
- Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg daily equivalent of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.
- Known history of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 28, 2022
First Posted
July 5, 2022
Study Start
May 30, 2023
Primary Completion
February 9, 2025
Study Completion
February 9, 2025
Last Updated
June 26, 2025
Record last verified: 2025-06