A Phase 1/1b Safety Study of PRGN-3006 Adoptive Cellular Therapy in Patients With CD33-Positive Relapsed or Refractory Acute Myeloid Leukemia, Minimal Residual Disease Positive Acute Myeloid Leukemia, and Higher Risk Myelodysplastic Syndrome PRGN-3006 ADOPTIVE CELLULAR THERAPY

What's the purpose of this trial?

This is a first-in-human dose escalation/dose expansion study to evaluate the safety and identify the best dose of modified immune cells, PRGN-3006 (autologous chimeric antigen receptor (CAR) T cells), in adult patients with relapsed or refractory acute myeloid leukemia (AML), Minimal Residual Disease (MRD) positive acute myeloid leukemia or higher risk myelodysplastic syndrome (MDS). Autologous CAR T cells are modified immune cells that have been engineered in the laboratory to specifically target a protein found on tumor cells and kill them.



This trial is currently open and accepting patients.

What will happen during the trial?

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

Inclusion Criteria:

  • Participants must be diagnosed with either relapsed or refractory AML (including extramedullary disease ), MRD-positive AML, or higher risk MDS.
  • Absolute lymphocyte count ≥ 0.2 k/μL.
  • Karnofsky performance status score ≥60%.
  • Life expectancy ≥ 12 weeks 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).
  • Bilirubin ≤ 2.0 mg/dL or total bilirubin ≤ 3.0 x ULN 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 ULN.
  • 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. Note: Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for at least 1 year following study treatment (T cell infusion); should a woman participant or female partner of a male participant become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately.
  • Participant has a matched bone marrow donor and is otherwise able to receive a bone marrow transplant (dose escalation phase only and for participants with MRD-positive AML)
  • Participants who have undergone allo-SCT and/or donor lymphocyte infusion (DLI) are eligible if they are at least 3 months post SCT, prior to apheresis, atleast 30 days post last DLI prior to apheresis, have not received treatment or prophylaxis for GVHD 6 weeks before administration of CAR T cells, have no active GVHD.
  • All participants must have the ability to understand and willingness to sign a written informed consent.

Exclusion Criteria:

  • Diagnosis of acute promyelocytic leukemia (APL M3): t(15;17)(q22;q12); (promyelocytic leukemia [PML]/retinoic acid receptor [RAR] alpha [a]) and variants excluded.
  • Participants with peripheral blood blasts >35%
  • 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 ( i.e. no blasts in cerebrospinal fluid [CSF] by cytology and flow cytometry) will be eligible.
    Prior treatment with investigational CD33 targeting CAR T therapy for any disease.
  • Prior treatment with licensed or investigational CD33 targeting monoclonal antibody or antibody drug conjugate within 6 months of apheresis.
  • Participants enrolled in another investigational therapy protocol for their disease within 14 days or 5 half-lives of apheresis, 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 requirements.
  • 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 (e.g. cervix) may enroll irrespective of the time of diagnosis.
  • Pregnant and lactating women are excluded from this study
  • 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).
  • Participant, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.


Additional Trial Information

Phase 1

Enrollment: 88 patients (estimated)

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Published Results

Phase 1/1b Safety Study of Prgn-3006 Ultracar-T in Patients with Relapsed or Refractory CD33-Positive Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndromes

November 15, 2022

As of July 15, 2022 data cut-off, 24 pts have been treated in C1 (n=10) and C2 (n=14). The study enrolled 20 r/r AML, 1 CMML, and 3 MDS pts with a median age of 60.5 years (33-77). Pts were heavily pre-treated with a median of 3 prior regimens (range, 1-9) and 62.5% of pts (n=15) had prior allogeneic hematopoietic cell transplantation (alloHCT). Pts treated in C1 and C2 received 1.8 to 50 x 106 and 4.4 to 83 x 106 UltraCAR-T cells via intravenous (IV) infusion respectively.
PRGN-3006 infusion at up to 1x106 cells/kg was well tolerated with similar safety profile for pts treated in C1 and C2. There have been no deaths, dose-limiting toxicities (DLTs), or unexpected on-target/off-target toxicities related to PRGN-3006, and no use of the kill switch as of data cut-off. There have been no cases of bone marrow aplasia. Grade 1 cytokine release syndrome (CRS) occurred in 3/10 pts in C1 ((DL1 (n=1), and DL3 (n=2)), and 7/14 pts in C2 ((DL1 (n=1), DL2 (n=2) and DL3 (n=4)). Grade 2 CRS occurred in 3/10 pts in C1 ((DL1 (n=1), and DL3 (n=2)) and 3/14 pts in C2 (DL3 (n=3)). Only 1 pt (DL1, C1) had transient grade 3 CRS that resolved in < 24 hours with tocilizumab and dexamethasone. Plasma levels of IL-15 did not increase with treatment confirming mbIL15 is not shed.

A dose dependent expansion of PRGN-3006 was observed in peripheral blood and bone marrow in both C1 and C2 patients with durable in vivo persistence of UltraCAR-T in the blood for up to 7 months post infusion. Peak expansion in the blood was significantly higher (> 1 log10) in pts treated in C2 with lymphodepletion compared to C1 without lymphodepletion at the same dose level, with the highest peak expansion observed in subjects treated in Cohort 2 at DL3. UltraCAR-T cells expanded in the bone marrow of pts treated in C1 and C2 with the highest peak bone marrow expansion in pts treated in C2 at DL3.

Bone marrow blasts were reduced following treatment in 7/14 (50%) of lymphodepleted pts (C2), with 4 pts experiencing a decrease to ≤5%. AML pts in Cohort 2 (n=10) demonstrated a 30% objective response rate: 1 CRi was bridged to alloHCT and remains in a measurable residual disease negative CR 18 months post-transplant; 1 CRh with complete cytogenetic remission and NGS clearance; and 1 PR in a pt with isolated extramedullary leukemia. No objective responses were observed in CMML (n=1) or MDS (n=3) pts treated to date on the study. In non-lymphodepleted pts (C1), 1/10 pts had durable stable disease lasting > 7 months with persistence of UltraCAR-T cells.

Trial Locations

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Moffitt Cancer Center Magnolia Campus

Tampa, FL

Open and Accepting


Mayo Clinic (Rochester)

Rochester, MN

Open and Accepting
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