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

Sponsored by:	Penn State University
Information provided by:	Penn State University
ClinicalTrials.gov Identifier:	NCT00860522

Purpose

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.

Condition	Intervention	Phase
Leukemia	Drug: JVRS-100	Phase I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Crossover Assignment, Safety/Efficacy Study
Official Title:	A Phase I Trial of the Immunostimulant JVRS-100 for the Treatment of Patients With Relapsed or Refractory Leukemia

Resource links provided by NLM:

MedlinePlus related topics: Leukemia, Adult Acute Leukemia, Adult Chronic

U.S. FDA Resources

Further study details as provided by Penn State University:

Primary Outcome Measures:

Evaluate the safety and tolerability of JVRS-100 for the treatment of patients with relapsed/refractory leukemia. [ Time Frame: Day 30 of cycle #1 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Define parameters of immune activation after JVRS-100 therapy. [ Time Frame: Day 30 of cycles #1 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	23
Study Start Date:	March 2009
Estimated Study Completion Date:	October 2012
Estimated Primary Completion Date:	October 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Phase I: Experimental 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.	Drug: JVRS-100 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
Phase II: Experimental 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.	Drug: JVRS-100 Change to Stage 2 with starting dose of 4.0 µg/Kg D1,8,15 if no toxicity level by Level 5.

Arms

Assigned Interventions

Phase I: Experimental

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.

Drug: JVRS-100

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

Phase II: Experimental

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.

Drug: JVRS-100

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

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00860522

Contacts

Contact: David F. Claxton, MD	717-531-8401	dclaxton@psu.edu
Contact: Tara Nisbet, RN	717-531-0003 ext 285453	tnisbet@psu.edu

Locations

United States, Pennsylvania
Penn State Milton S. Hershey Medical Center	Recruiting
Hershey, Pennsylvania, United States, 17033
Contact: David F Claxton, MD 717-531-8401 dclaxton@psu.edu
Contact: Tara Nisbet, RN 717-531-0003 ext 285453 tnisbet@psu.edu

Sponsors and Collaborators

Penn State University

Investigators

Principal Investigator:

David F Claxton, MD

Milton S. Hershey Medical Center

More Information

No publications provided

Responsible Party:	Penn State Milton S. Hershey Medical Center ( David Claxton, MD )
Study ID Numbers:	08-031
Study First Received:	March 11, 2009
Last Updated:	March 11, 2009
ClinicalTrials.gov Identifier:	NCT00860522 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Penn State University:

relapsed leukemia
refractory leukemia

Study placed in the following topic categories:

Leukemia

Additional relevant MeSH terms:

Leukemia
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on September 10, 2009