A Phase I Trial of the Immunostimulant JVRS-100 for the Treatment of Patients With Relapsed or Refractory Leukemia

JVRS-100 for the Treatment of Patients With Relapsed or Refractory Leukemia

Sponsors

Lead sponsor: Milton S. Hershey Medical Center

Source Milton S. Hershey Medical Center
Brief Summary

This is a Phase 1, open-label, dose escalation study of JVRS-100. The study will proceed in 2 stages to minimize the number of patients treated at doses substantially below the recommended phase 2 dose. In stage 1, an accelerated titration schema will be followed with one patient at each dose level. Stage 2 will commence after a dose limiting toxicity is observed in stage 1 or after the maximum dose for stage 1 is reached. Stage 2 will follow a modified Fibonacci schema with 3-6 subjects at each dose level until a recommended phase 2 dose is determined. The cohort will then be expanded to a maximum of 12 patients to more fully evaluate the recommended phase 2 dose.

Detailed Description

This is a Phase 1, open-label, dose escalation study of JVRS-100. The study will proceed in 2 stages to minimize the number of patients treated at doses substantially below the recommended phase 2 dose. In stage 1, cohorts of three will be treated at each dose level however doses will be doubled from level to level. Stage 2 will commence after a dose limiting toxicity is observed in stage 1 or after the maximum dose for stage 1 is reached. Stage 2 will follow a modified Fibonacci schema with 3-6 subjects at each dose level until a recommended phase 2 dose is determined. The cohort will then be expanded to a maximum of 12 patients to more fully evaluate the recommended phase 2 dose. The Principal Investigator will assign dose level to be administered to all patients.

Overall Status Completed
Start Date March 1, 2009
Completion Date February 20, 2017
Primary Completion Date October 31, 2014
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Tolerability of JVRS-100 Day 30 of cycle #1
Secondary Outcome
Measure Time Frame
Define parameters of immune activation after JVRS-100 therapy. Day 30 of cycle #1
Enrollment 11
Condition
Intervention

Intervention type: Drug

Intervention name: JVRS-100

Description: Level 1: 0.5 µg/Kg D1,8,15; Level 2: 1.0 µg/Kg D1,8,15; Level 3:2.0 µg/Kg 1,15; Level 4: 2.0 µg/Kg D1,8,15; Level 5: 4.0 µg/Kg D1,15

Arm group label: Phase I

Intervention type: Drug

Intervention name: JVRS-100

Description: Change to Stage 2 with starting dose of 4.0 µg/Kg D1,8,15 if no toxicity level by Level 5.

Arm group label: Phase II

Eligibility

Criteria:

Inclusion Criteria:

- 18 years of age

- Histologically or cytologically documented relapsed or refractory acute leukemia

- Unlikely to benefit from standard therapy in the opinion of the investigator or refuse standard therapy

- ECOG performance status 0-2

- Adequate renal and hepatic function

- No hematologic criteria for WBC, Hbg or platelets

- Negative virology screen for HIV, hepatitis B surface antigen & hepatitis C

- Female patients of childbearing potential must have a negative serum pregnancy test

- Male & female patients must agree to use a medically acceptable barrier and/or chemical contraceptive method during the study and for a minimum of 3 months afte the last dose of study treatment.

- Patients post blood or marrow transplant should demonstrate a circulating CD8 count of at lest 200 cells/ul

Exclusion Criteria:

- Active CNS leukemia

- Current concomitant chemotherapy, radiation therapy or immunotherapy

- Receipt of any investigational agent within 28 days of first dose of JVRS-100

- Persistent clinically significant toxicity from prior anticancer therapy that is > Grade 2 (NCI CTCAE v3.0)

- Bone marrow or stem cell transplant within 3 months prior to first dose of JVRS-100

- Chronic administration of immunosuppressive agents within 14 days of first dose of JVRS-100. Use of inhaled steroids, nasal sprays, eye drops, and topical creams for small body areas is allowed.

- Pregnant or lactating

- History of prior malignancy other than leukemia within the past 5 years, excluding basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix

- Patients with a systemic fungal, bacterial, viral, or other infection not controlled

- Any condition which, in the opinion of the investigator, would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
David F Claxton, MD Principal Investigator Milton S. Hershey Medical Center
Location
facility Penn State Hershey Cancer Institute
Location Countries

United States

Verification Date

April 2019

Responsible Party

Responsible party type: Principal Investigator

Investigator affiliation: Milton S. Hershey Medical Center

Investigator full name: David F. Claxton, MD

Investigator title: Professor of Medicine

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Phase I

Arm group type: Experimental

Description: Three patients will be enrolled at dose Level 1. If the patient does not completed the three infusion of JVRS-100 during cycle 1 for reason other than toxicity, another patient will be accrued at the same dose level.

Arm group label: Phase II

Arm group type: Experimental

Description: 3 patients will be enrolled at a given dose level. If one of these patients experiences a dose limiting toxicity, an additional 3 patients will be enrolled at the given dose level. If the 1st 2 subjects enrolled and treated at a given dose experience dose limiting toxicities, no additional subjects will be enrolled at that dose. Dose escalation may proceed if < 2/6 patients at a given dose level experience a LDT. If ≥ 2/6 patients experience a DLT at a given dose level, the next lower dose level will be considered the RP2D. If a patient does not complete the 3 infusions of JVRS-100 during Cycle 1 for reasons other than toxicity, another patient will be accrued at the same dose level. Once the RP2D is established, the cohort will be expanded to a total of 12 patients.

Patient Data No
Study Design Info

Allocation: Non-Randomized

Intervention model: Crossover Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov