- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04855253
Study of E7777 Prior to Kymriah for R/R DLBCL
Phase I/II Trial Using E7777 to Enhance Regulatory T-Cell Depletion Prior to Tisagenlecleucel (Kymriah) Therapy for Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Cancer Center Clinical Trials Office
- Phone Number: 612-676-4200
- Email: ccinfo@umn.edu
Study Locations
-
-
Minnesota
-
Minneapolis, Minnesota, United States, 55455
- Recruiting
- University of Minnesota, Masonic Cancer Center
-
Principal Investigator:
- Veronika Bachanova, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
Diagnosis of a relapse or refractory (r/r) large B cell lymphoma, for which treatment with Kymriah is planned, including:
- diffuse large B-cell lymphoma (DLBCL) not otherwise specified,
- high grade B-cell lymphoma
- DLBCL arising from follicular lymphoma
Considered at high risk for progression after CAR-T therapy by meeting one or more of the following factors:
- refractory to last line of therapy
- myc over expression >40% in any prior biopsy
- ≥2 sites of extranodal disease
- Received two or more lines of systemic therapy
- Has secured insurance coverage for Kymriah administration either in the outpatient or inpatient setting.
- Age 18 years or older at the time of signing consent.
- ECOG performance status of 0, 1, or 2
Adequate bone marrow reserve defined as:
- Absolute neutrophil count (ANC) > 1,000/mm^3
- Platelets ≥ 50,000/mm^3 (transfusion support can be provided)
- Hemoglobin >8.0 mg/dl (transfusion support can be provided) Bone marrow involvement at disease assessment is an exclusion as these patients are at an increased risk of severe CRS and/or neurotoxicity
Adequate organ function at enrollment and within 14 days of planned E7777 treatment including:
- renal function: eGFR ≥ 50 mL/min/1.73 m^2
- liver function: ALT ≤ 3 times the upper limit of normal (ULN) for age, AST ≤ 3 times the ULN, total bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN (if liver is involved by lymphoma, the exception are allowed upon approval of PI)
- albumin ≥ 3.0 g/dl
- Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea (CTCAE v5) and pulse oxygenation SpO2 > 91% on room air. Pulmonary function tests within 28 days of enrollment: >50% corrected DLCO and FEV1
- Hemodynamically stable and LVEF ≥ 50% confirmed by echocardiogram or MUGA
- Life expectancy ≥12 weeks in the opinion of the enrolling investigator as documented in the medical record
- Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use birth control for at least 30 days after study treatment or at least at least 4 months after the final dose of CY, whichever is longer Female participants: Two forms of birth control, one of which must be a barrier method, for example: use of intrauterine device (IUD) or oral contraceptives, plus a barrier method such as a condom, diaphragm or cervical cap Male participants: If possible to father a child (unless a successful vasectomy with confirmed azoospermia) participant and female partner, must use adequate contraception
- Written voluntary consent prior to the performance of any research related tests or procedures
Exclusion Criteria:
- Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to study enrollment to rule out pregnancy. All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing)
- Known bone marrow involvement, if history of bone marrow involvement must have a BM biopsy to rule-out current involvement
- Prior allogeneic transplant
- Ocular disease or complaints visual acuity impairment, color or shape distortion, or blurred vision - potential participants are required to have an ophthalmological examine as part of screening
- Known CNS involvement by malignancy - if clinically suspicious, must be ruled-out by examination of cerebrospinal fluid (CSF) by flow cytometry
- Uncontrolled active hepatitis B or hepatitis C
- Active or inactive HIV infection
- Untreated active bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to enrollment)
- History of heart failure or pulmonary edema, evidence of pleural effusion or active lower extremity edema
- Uncontrolled unstable angina and/or myocardial infarction within 3 months of enrollment
- Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Dose level 1 : E7777 at 5 mcg/kg
Single dose of E7777 given on Day -7 two days prior to the start of lymphodepleting chemotherapy
|
E7777 is a recombinant fusion toxin consisting of full-length human IL-2 fused to the catalytic domains of diphtheria toxin.
E7777 is preferentially bound to and internalized by cells expressing the high affinity form (CD25+) of the IL-2 receptor.
|
Experimental: Dose level 1 : E7777 at 7 mcg/kg
Single dose of E7777 given on Day -7 two days prior to the start of lymphodepleting chemotherapy
|
E7777 is a recombinant fusion toxin consisting of full-length human IL-2 fused to the catalytic domains of diphtheria toxin.
E7777 is preferentially bound to and internalized by cells expressing the high affinity form (CD25+) of the IL-2 receptor.
|
Experimental: Dose level 1 : E7777 at 9 mcg/kg
Single dose of E7777 given on Day -7 two days prior to the start of lymphodepleting chemotherapy
|
E7777 is a recombinant fusion toxin consisting of full-length human IL-2 fused to the catalytic domains of diphtheria toxin.
E7777 is preferentially bound to and internalized by cells expressing the high affinity form (CD25+) of the IL-2 receptor.
|
Experimental: MTD from phase 1
Single dose of E7777 (Maximum tolerated dose level identified in phase 1) given on Day -7 two days prior to the start of lymphodepleting chemotherapy
|
E7777 is a recombinant fusion toxin consisting of full-length human IL-2 fused to the catalytic domains of diphtheria toxin.
E7777 is preferentially bound to and internalized by cells expressing the high affinity form (CD25+) of the IL-2 receptor.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of participants experiencing dose limiting toxicity events
Time Frame: 28 Days Post E7777 infusion
|
Dose Limiting Toxicity (DLT) is defined as any of the following events based on CTCAE v5 from the 1st infusion of E7777 through 21 days after the administration of tisagenlecleucel (~28 days after E7777).
|
28 Days Post E7777 infusion
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of participants experiencing adverse events
Time Frame: 100 days Post E7777 infusion
|
Number of participants experiencing adverse events related to E7777 to determine safety of the E7777
|
100 days Post E7777 infusion
|
Number of participants experiencing disease free survival (DFS)
Time Frame: 1 year Post E7777 infusion
|
Number of participants experiencing disease free survival (DFS) at 1 year
|
1 year Post E7777 infusion
|
Number of participants experiencing overall survival (OS)
Time Frame: 1 year Post E7777 infusion
|
Number of participants experiencing overall survival (DFS) at 1 year
|
1 year Post E7777 infusion
|
Number of non-relapse mortality incidents at day 100
Time Frame: 100 days Post E7777 infusion
|
Number of participants experiencing non-relapse mortality at day 100 post E7777 infusion
|
100 days Post E7777 infusion
|
Number of Grade 3 or 4 cytokine release syndrome (CRS) incidents
Time Frame: 28 Days Post E7777 infusion
|
Number of participants experiencing Grade 3 or 4 cytokine release syndrome (CRS) after tisagenlecleucel therapy.
|
28 Days Post E7777 infusion
|
Number of Grade 3 or 4 immune effector cell associated neurotoxicity (ICAN) syndrome incidents
Time Frame: 28 Days Post E7777 infusion
|
Number of participants experiencing Grade 3 or 4 immune effector cell associated neurotoxicity (ICAN) syndrome after tisagenlecleucel therapy.
|
28 Days Post E7777 infusion
|
Collaborators and Investigators
Investigators
- Principal Investigator: Veronika Bachanova, MD, Masonic Cancer Center, University of Minnesota
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2020LS100
- MT2020-27 (Other Identifier: University of Minnesota Masonic Cancer Center)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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