Description:
This study is to determine the safety and best dose of PRGN-3006 T Cells
Title
- Brief Title: PRGN-3006 Adoptive Cellular Therapy Relapsed or Refractory 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 Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndrome
Clinical Trial IDs
- ORG STUDY ID:
MCC-19862
- NCT ID:
NCT03927261
Conditions
- Myelodysplastic Syndromes
- Acute Myeloid Leukemia
Interventions
Drug | Synonyms | Arms |
---|
PRGN-3006 T Cells | | Dose Escalation and Dose Expansion of PRGN-3006 |
Purpose
This study is to determine the safety and best dose of PRGN-3006 T Cells
Detailed Description
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 acute myeloid leukemia (AML) or higher risk myelodysplastic syndromes (MDS).
This study will enroll in two phases: an initial dose escalation phase followed by a dose
expansion phase.
Trial Arms
Name | Type | Description | Interventions |
---|
Dose Escalation and Dose 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. | |
Eligibility Criteria
Inclusion Criteria:
- Participants must be diagnosed with either relapsed or refractory 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).
- 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. 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 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
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.
- 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 CAR T therapy for any disease.
- Participants enrolled in another investigational therapy protocol for their disease
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
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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of Participants who Experience Dose Limiting Toxicities (DLTs) |
Time Frame: | Up to Day 42 |
Safety Issue: | |
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[2]) that does not resolve within 7 days |
Secondary Outcome Measures
Measure: | Disease Progression in AML Participants |
Time Frame: | Up to 15 years |
Safety Issue: | |
Description: | Proportion of AML patients achieving partial response (PR), complete response (CR), and/or morphologic leukemia free state (MLFS) by ELN Response Criteria in AML. CRh (complete PRGN-3006 T cells in patients with AML/MDS remission with partial hematological recovery) will also be captured, defined as <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 |
Safety Issue: | |
Description: | Proportion of MDS patients achieving a response (CR, PR or Marrow CR) as defined in International Working Group (IWG) 2006 Criteria. |
Measure: | Rate of Absolute Neutrophil Count Recovery |
Time Frame: | Day 28 |
Safety Issue: | |
Description: | Rate of Absolute Neutrophil count recovery (>0.5 x 10^9/L) |
Measure: | Absolute Lymphocyte Count (ALC) |
Time Frame: | Baseline |
Safety Issue: | |
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 |
Safety Issue: | |
Description: | Number of PRGN-3006 T Cells present in patients treated with PRGN-3006 |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | H. Lee Moffitt Cancer Center and Research Institute |
Trial Keywords
Last Updated
May 24, 2021