Acute Myeloid LeukemiaPhase 1NCT03927261
PRGN-3006 Adoptive Cellular Therapy for CD33-Positive Relapsed or Refractory AML, MRD Positive AML or Higher Risk MDS
A Phase 1 study testing PRGN-3006 T Cells in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by Precigen, Inc at 2 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Myelodysplastic Syndromes
- What is being tested?
- PRGN-3006 T Cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 88 participants
- Where
- 2 sitesUnited States
- Study dates
- 20 May 2019to 1 Aug 2025
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Mayo Clinic
Rochester, Minnesota, 55905
H Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
Official title: 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
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.
Read the detailed description
This is a multi-center, nonrandomized, 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 AML, MRD-positive AML, or higher risk MDS.
This study has completed the dose escalation phase and is further evaluating PRGN-3006 at the identified dose in the dose expansion phase.
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndromes
- Being tested
- PRGN-3006 T Cells
- Keywords
- AML, MDS
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PRGN-3006 T CellsDrug
Participants will receive up to 2 intravenous (IV) administrations of PRGN-3006 T Cells with or without lymphodepletion and will be monitored for safety, efficacy, and correlative endpoints for up to 12 months following infusion.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation and Dose Expansion of PRGN-3006 | Experimental | Participants will be treated in dose expansion phase to evaluate the safety and efficacy of the identified dose of PRGN-3006. Receives: Drug: PRGN-3006 T Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants who Experience Dose Limiting Toxicities (DLTs)
Incidence of dose limiting toxicity (DLT) as defined in the protocol
Measured: Up to Day 42
Number of Participants who Experience Treatment Emergent Adverse Events (TEAEs)
Systemic toxicity in general and hematologic toxicity in specific will be assessed through the capture of TEAEs at each study visit and through laboratory assessments throughout the study. The severity of the TEAEs will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 scale.
Measured: Up to 12 months post treatment
Secondary outcomes (5)
Disease Progression in AML Participants
Proportion of AML patients achieving partial response (PR), complete response (CR), CR with incomplete count recovery (CRi), and/or morphologic leukemia free state (MLFS) by ELN Response Criteria in AML. CRh will also be captured, defined as <5% of blasts in the bone marrow, no evidence of disease, and partial recovery of peripheral blood counts.
Measured: Up to 12 months post treatment
Disease Response in MDS Patients
Proportion of MDS patients achieving a response (CR, PR or Marrow CR) as defined in International Working Group (IWG) 2006 Criteria.
Measured: Up to 12 months post treatment
Rate of Absolute Neutrophil Count Recovery
Rate of Absolute Neutrophil count recovery (>0.5 x 10^9/L)
Measured: Day 28
Absolute Lymphocyte Count (ALC)
ALC including CD4/CD8 subsets by flow cytometry at baseline (at apheresis) in patients who have successful versus failed PRGN-3006 production.
Measured: Baseline
Number of PRGN-3006 T Cells
Number of PRGN-3006 T Cells present in patients treated with PRGN-3006
Measured: Up to 12 months post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2019
- Study start20 May 2019
- Primary completion1 Aug 2024
- Study completion1 Aug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 88 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Precigen, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Amy R. Lankford, PhD, Study director, Precigen, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03927261
- Sponsor's protocol ID
- PRGN3006-001
- Status last verified
- Nov 2024
- First submitted
- 23 Apr 2019
- Last updated
- 8 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Sallman DA, Elmariah H, Sweet K, Talati C, Mishra A, Cox CA, Semnani R, Shah RR, Sabzevari H, Chakaith M, Uthuppan J, Lankford A, Wang C, Padron E, Kuykendall AT, Komrokji RS, Lancet JE, Davila ML, Bejanyan N. 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. Blood. 2021; 138(Supplement 1):825.
Sallman DA, Elmariah H, Sweet K, Mishra A, Cox CA, Chakaith M, Semnani R, Shehzad S, Anderson A, Sabzevari H, Lankford A, Chan O, SanchezMolina L, Wang C, Padron E, Kuykendall A, Komrokji RS, Lancet JE, Davila ML, Bejanyan N. 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. Blood. 2022; 140(Supplement 1):10313-10315.
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03927261
- Acronym / sponsor ID
- PRGN3006-001
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndromes
- Keywords
- AML, MDS
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 88 participants (estimated)
- Lead sponsor
- Precigen, IncIndustry (pharma, biotech, devices)
- Study start
- 20 May 2019 (actual)
- Primary completion
- 1 Aug 2024 (actual)
- Study completion
- 1 Aug 2025 (estimated)
- First posted
- 25 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a multi-center, nonrandomized, 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 AML, MRD-positive AML, or higher risk MDS.
This study has completed the dose escalation phase and is further evaluating PRGN-3006 at the identified dose in the dose expansion phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation and Dose Expansion of PRGN-3006 | Experimental | Drug: PRGN-3006 T CellsParticipants will be treated in dose expansion phase to evaluate the safety and efficacy of the identified dose of PRGN-3006. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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).
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PRGN-3006 T CellsParticipants will receive up to 2 intravenous (IV) administrations of PRGN-3006 T Cells with or without lymphodepletion and will be monitored for safety, efficacy, and correlative endpoints for up to 12 months following infusion. | Drug | Dose Escalation and Dose Expansion of PRGN-3006 |
Primary outcome
Number of Participants who Experience Dose Limiting Toxicities (DLTs)
Time frame: Up to Day 42
Incidence of dose limiting toxicity (DLT) as defined in the protocol
Number of Participants who Experience Treatment Emergent Adverse Events (TEAEs)
Time frame: Up to 12 months post treatment
Systemic toxicity in general and hematologic toxicity in specific will be assessed through the capture of TEAEs at each study visit and through laboratory assessments throughout the study. The severity of the TEAEs will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 scale.
5 secondary outcomes
Disease Progression in AML Participants
Time frame: Up to 12 months post treatment
Disease Response in MDS Patients
Time frame: Up to 12 months post treatment
Rate of Absolute Neutrophil Count Recovery
Time frame: Day 28
Absolute Lymphocyte Count (ALC)
Time frame: Baseline
Number of PRGN-3006 T Cells
Time frame: Up to 12 months post treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2024.
- BackgroundSallman DA, Elmariah H, Sweet K, Talati C, Mishra A, Cox CA, Semnani R, Shah RR, Sabzevari H, Chakaith M, Uthuppan J, Lankford A, Wang C, Padron E, Kuykendall AT, Komrokji RS, Lancet JE, Davila ML, Bejanyan N. 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. Blood. 2021; 138(Supplement 1):825.
- BackgroundSallman DA, Elmariah H, Sweet K, Mishra A, Cox CA, Chakaith M, Semnani R, Shehzad S, Anderson A, Sabzevari H, Lankford A, Chan O, SanchezMolina L, Wang C, Padron E, Kuykendall A, Komrokji RS, Lancet JE, Davila ML, Bejanyan N. 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. Blood. 2022; 140(Supplement 1):10313-10315.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amy R. Lankford, PhD study director
Precigen, Inc
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PRGN-3006 T Cells in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by Precigen, Inc at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 8 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants who Experience Dose Limiting Toxicities (DLTs) (time frame: Up to Day 42). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03927261, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2024.