This study is to determine the safety and best dose of PRGN-3006 T Cells.
- Brief Title: PRGN-3006 Adoptive Cellular Therapy Relapsed or Refractory CD33-Positive AML or High Risk MDS
- Official Title: A Phase 1/1b Safety Study of PRGN-3006 Adoptive Cellular Therapy in Patients With Relapsed or Refractory CD33-Positive Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndrome
Clinical Trial IDs
- ORG STUDY ID:
- NCT ID:
- Myelodysplastic Syndromes
- Acute Myeloid Leukemia
|PRGN-3600 T Cells||Dose Escalation and Expansion of PRGN-3006|
Thi study is to determine the safety and best dose of PRGN-3006 T Cells.
This is a single center, nonrandomized, investigator-initiated Phase 1/1b safety and
tolerability study. The safety and tolerability of PRGN-3006 T cells will be assessed
following intravenous administration of escalating doses in patients with relapsed or
refractory CD33-positive acute myeloid leukemia (AML) or higher risk myelodysplastic
The study will enroll in two phases: an initial dose escalation phase followed by a dose
|Dose Escalation and Expansion of PRGN-3006||Experimental||Participants will be treated in dose escalation phase to identify the safety and maximum tolerated dose (MTD) of PRGN-3006. Doses of genetically modified T cells indicated as CAR-T cell dose/kg recipient weight Dose Level -1: >10^4 but </=3x10^4 cells/kg Dose Level 1: >3x10^4 but </=10^5 cells/kg Dose Level 2: >10^5 but </= 3x10^5 cells/kg Dose Level 3:>3x10^5 but </= 10^6 cells/kg|
- Participants must be diagnosed with either relapsed or refractory CD33+ AML or higher
- Absolute lymphocyte count ≥ 0.2 k/μL.
- Karnofsky performance status score ≥60%.
- Life expectancy 12 weeks or more from the time of enrollment.
- Pretreatment calculated or measured creatinine clearance (absolute value) of ≥ 40
mL/minute or Cr > 2x upper limit of normal (ULN).
- Serum bilirubin ≤ 2.0 mg/dL or total bilirubin ≤ 3.0 x IULN with direct bilirubin
within normal range in Participants with well documented Gilbert's syndrome or
hemolysis or who require regular blood transfusions
- Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) < 3.0 x IULN.
- Ejection fraction measured by echocardiogram (ECHO) or multi gated acquisition scan
(MUGA) > 45%.
- Participant does not require supplemental oxygen or mechanical ventilation AND has an
oxygen saturation by pulse oximetry of ≥ 92% or higher on room air.
- Negative serum pregnancy test.
- Participant has a matched bone marrow donor and is otherwise able to receive a bone
marrow transplant (dose escalation part only)
- Participants who have undergone allo-SCT are eligible if they are at least 3 months
post SCT, have relapsed AML/MDS as defined above, are not on treatment or prophylaxis
for GVHD for at least 6 weeks before administration of CAR T cells, and have no active
- All Participants must have the ability to understand and willingness to sign a written
- Diagnosis of acute promyelocytic leukemia
- Participants with extramedullary disease as their sole site of relapsed AML.
- Known central nervous system (CNS) leukemic involvement that is refractory to
intrathecal chemotherapy and/or cranio-spinal radiation; Participants with a history
of CNS disease that have been effectively treated to complete remission will be
- Prior treatment with investigational CAR-T therapy for any disease.
- Participants enrolled in another investigational therapy protocol for AML within 14
days or 5 half-lives of enrollment, whichever is shorter.
- Ongoing uncontrolled serious infection, symptomatic congestive heart failure, unstable
angina pectoris, uncontrolled cardiac arrhythmia, poorly controlled pulmonary disease
or psychiatric illness/social situations that would limit compliance with study
- Human immunodeficiency virus (HIV) seropositivity, or active hepatitis B or C
infection based on testing performed within 28 days of enrollment.
- Participants requiring agents other than hydroxyurea to control blast counts within 14
days of study enrollment.
- Participants with presence of other active malignancy within 1 year of study entry.
- Participants with adequately resected basal or squamous cell carcinoma of the skin, or
adequately resected carcinoma in situ may enroll irrespective of the time of
- Pregnant and breastfeeding women.
- History of allergic reactions attributed to compounds of similar chemical or
biological composition to cetuximab (anti-EGFR).
- Active autoimmune disease requiring systemic immunosuppressive therapy (i.e. > 10mg of
prednisone daily or equivalent).
- Participants who, in the opinion of the investigator, may not be able to comply with
the safety monitoring requirements of the study.
|Maximum Eligible Age:||N/A|
|Minimum Eligible Age:||18 Years|
Primary Outcome Measures
|Measure:||Number of Participants who Experience Dose Limiting Toxicities (DLTs)|
|Time Frame:||Up to Day 42|
|Description:||A dose limiting toxicity (DLT) is any of the following and is determined by the investigator to be related to study drug:
Aplastic bone marrow, defined by marrow cellularity <5% at Day 28 in the absence of residual disease and confirmed at Day 42.
Treatment-emergent CRS of Grade 4 that does not resolve to Grade ≤2 within 72 hours, despite optimal treatment
Treatment-emergent CRS of Grade 3 that does not resolve to Grade ≤2 within 2 weeks, despite optimal treatment;
Treatment-related Grade 4-5 allergic reactions
Treatment-related non-reversible Grade 3 (< 14 days), or any Grade 4-5 autoimmune reactions related to the study cell infusion.
Central neurologic toxicity Grade ≥3 lasting more than 14 days
Grade 5 Cytokine Release Syndrome (CRS)
Tumor Lysis Syndrome ≥ IV (Cairo and Bishop, 2004) that does not resolve within 7 days|
Secondary Outcome Measures
|Measure:||Disease Response in AML Participants|
|Time Frame:||up to 15 years|
|Description:||Proportion of AML Patients achieving Partial Response (PR), Complete Response (CR) and/or morphologic leukemia free state (MLFS) as indicated by ELN Response Criteria in AML. Complete Remission with Partial Hematological Recovery (CRh) will also be captured, defined as less than 5% of blasts in the bone marrow, no evidence of disease, and partial recovery of peripheral blood counts.|
|Measure:||Disease Response in MDS Patients|
|Time Frame:||Up to 15 years|
|Description:||Proportion of MDS Patients achieving Partial Response (PR), Complete Response (CR), or Marrow Complete Response as defined in International Working Group (IWG) 2006 Criteria|
|Measure:||Rate of Absolute Neutrophil Count Recovery|
|Time Frame:||Day 28|
|Description:||Rate of Absolute Neutrophil Count Recovery (>0.5 x 10^9/L)|
|Measure:||Absolute Lymphocyte Count (ALC)|
|Description:||ALC including CD4/CD8 subsets by flow cytometry at baseline (at apheresis) in patients who have successful versus failed PRGN-3006 production.|
|Measure:||Number of PRGN-3006 T Cells|
|Time Frame:||Up to 12 months post treatment|
|Description:||Number of PRGRN-3006 T Cells present in patients treated with PRGN-3006|
|Overall Status:||Not yet recruiting|
|Lead Sponsor:||H. Lee Moffitt Cancer Center and Research Institute|