PRGN-3006 Adoptive Cellular Therapy Relapsed or Refractory CD33-Positive AML or High Risk MDS

Acute Myeloid Leukemia Clinical Trial

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 Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03826082
• Other study ID #: MCC-19862
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: April 1, 2019
• Est. completion date: April 1, 2035

Study information

• Verified date: January 2019
• Source: H. Lee Moffitt Cancer Center and Research Institute
• Contact: Leighann Montoya
• Phone: 813-745-3762
• Email: Leighann.Montoya[@]moffitt.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is to determine the safety and best dose of PRGN-3006 T Cells.

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 CD33-positive acute myeloid leukemia (AML) or higher risk myelodysplastic syndromes (MDS).

The study will enroll in two phases: an initial dose escalation phase followed by a dose expansion phase.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 56
• Est. completion date: April 1, 2035
• Est. primary completion date: April 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participants must be diagnosed with either relapsed or refractory CD33+ AML or higher risk MDS

• 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 GVHD.

• All Participants must have the ability to understand and willingness to sign a written informed consent.

Exclusion Criteria:

• 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 eligible.

• 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 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 may enroll irrespective of the time of diagnosis.

• 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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• PRGN-3600 T Cells
All eligible participants enrolled into each phase will undergo leukapheresis for manufacture of PRGN-3006 T cells. Participants enrolled to Cohort 2 will undergo lymphodepletion five days prior to the scheduled date of PRGN-3006 infusion. Participants will receive a single intravenous (IV) administration of PRGN-3006 T cells, and will be monitored for safety in the clinic for at least 7 days following infusion, and for safety, efficacy and correlative endpoints for up to 12 months following infusion.

Locations

Country	Name	City	State
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
H. Lee Moffitt Cancer Center and Research Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants who Experience Dose Limiting Toxicities (DLTs)	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	Up to Day 42
Primary	Number of Participants who Experience Treatment Related Adverse Events (AEs)	Systemic toxicity in general and hematologic toxicity in specific will be assessed through the capture of AEs at each study visit and through laboratory assessments throughout the study. The severity of the AEs will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 scale.	Up to 12 months post treatment
Secondary	Disease Response in AML Participants	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.	up to 15 years
Secondary	Disease Response in MDS Patients	Proportion of MDS Patients achieving Partial Response (PR), Complete Response (CR), or Marrow Complete Response as defined in International Working Group (IWG) 2006 Criteria	Up to 15 years
Secondary	Rate of Absolute Neutrophil Count Recovery	Rate of Absolute Neutrophil Count Recovery (>0.5 x 10^9/L)	Day 28
Secondary	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.	Baseline
Secondary	Number of PRGN-3006 T Cells	Number of PRGRN-3006 T Cells present in patients treated with PRGN-3006	Up to 12 months post treatment

External Links

•   Moffitt Cancer Center Clinical Trials Website