A Phase I Study of Intranodal Injection of Ad-ISF35 in Subjects With CLL/SLL - Full Text View

Sponsors and Collaborators:	Memgen, LLC University of California, San Diego
Information provided by:	Memgen, LLC
ClinicalTrials.gov Identifier:	NCT00783874

Purpose

This is a phase I, open label, non-randomized, single institution based clinical trial. Eligible subjects will receive a single dose of Ad-ISF35 injected directly into a selected lymph node under ultrasound guidance. The primary goal of this trial is to determine the maximum tolerated dose (MTD) of intranodal injection of Ad-ISF35.

Condition	Intervention	Phase
Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma	Biological: ISF35	Phase I

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

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Phase I, Open Label, Dose Escalation, Pharmacodynamic Study of Intranodal Injection of Adenovirus-CD154 (Ad-ISF35) in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.

Further study details as provided by Memgen, LLC:

Primary Outcome Measures:

Determine the safety and maximum tolerated dose (MTD) of Adenovirus-CD154 (Ad-ISF35) when injected directly into lymph nodes of patients with CLL/SLL. [ Time Frame: Duration of Trial ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Determine and monitor clinical and biological responses in patients treated with intranodal injections of Ad-ISF35. [ Time Frame: Duration of Trial ] [ Designated as safety issue: No ]
Determine pharmacodynamic (PD) parameters in patients treated with intranodal injections of ISF35. [ Time Frame: Duration of Trial ] [ Designated as safety issue: No ]

Enrollment:	15
Study Start Date:	September 2007
Study Completion Date:	September 2008
Primary Completion Date:	July 2008 (Final data collection date for primary outcome measure)

Intervention Details:

Ad-ISF35, a recombinant type V adenovirus encoding a recombinant humanized CD154 homolog (ISF35).

Detailed Description:

We will use a 3+3 dose escalation scheme with the following doses of Ad-ISF35:

Cohort # 1 1 x 10^10 viral particles (vp)

Cohort # 2 3 x 10^10 vp

Cohort # 3 1 x 10^11 vp

Cohort # 4 3 x 10^11 vp

The concentration of the viral preparation will be 5 x 10^11 vp/ml. Based on plaque forming unit (pfu) assays we have observed that approximately 20 viral particles are equivalent to 1 pfu. Dose escalations will occur after the patient(s) assigned to the prior dose level has been observed for 21 days after injection of ISF35. The recommended Phase II dose is expected to be the highest dose below the maximally tolerated dose (MTD) at which ≤1/6 patients experience dose-limiting toxicity (DLT) during the first 21 days of treatment. However, the final determination will also take into account any cumulative or delayed toxicity.

ISF35 has already been used in Phase I clinical trials. The trials demonstrated that ISF35 treatment is well-tolerated and patients did not experience any significant or unexpected adverse events. Patients reported flu-like symptoms from ISF35, which disappeared within one to three days.

ISF35 is an abbreviation for Immune Stimulatory Factor 35, an offspring of technology discovered by Dr. Thomas J. Kipps, MD, PhD, Professor, Department of Medicine and Deputy Director for Research,UCSD Moores Cancer Center.

Eligibility

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

Criteria

Inclusion Criteria:

Diagnosis of B-cell CLL/SLL including
- Lymphocytosis of monoclonal B-cells co-expressing ≥ one B-cell marker (CD19, CD20, or CD23) and CD5 in peripheral blood or lymph node AND
- Bone marrow with ≥ 30% mononuclear cells having the CLL/SLL phenotype.
Presence of at least ONE single accessible AND palpable lymph node in the supraclavicular, axillary, or inguinal regions. The size of the lymph nodes must be larger than 2x2 cm in the horizontal and perpendicular axes.
Intermediate or High risk, poor prognosis CLL/SLL
Indication for treatment as defined by the NCI Working Group Guidelines:
- Massive or progressive splenomegaly OR
- Massive lymph nodes, nodal clusters, or progressive lymphadenopathy OR
- Grade 2 or 3 fatigue OR
- Fever ≥ 100.5˚F or night sweats for greater than 2 weeks without documented infection OR
- Presence of weight loss ≥ 10% over the preceding 6 months OR
- Progressive lymphocytosis with an increase of ≥ 50% over a 2-month period or an anticipated doubling time of less than 12 months.
Males and females 18 years of age and older
Laboratory parameters as specified below:
- Hematologic: Hemoglobin ≥ 10 g/dL (may be post-transfusion); platelet count ≥ 50 x103/mm3
- Hepatic: Total Bilirubin < 2 X ULN, and ALT and AST < 2 x ULN
- Renal: Creatinine ≤ 2 X ULN
ECOG Performance Status ≤ 2
Anticipated survival of at least 3 months
For men and women of child-producing potential, use of effective barrier contraceptive methods during the study and for one month following treatment.
Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and return for the required assessments.
Negative test results for current/active infection with HIV-1, HIV-2, HTLV-1, HTLV-2, hepatitis A, B, C within 30 days of registration. (Antibody, antigen and nucleic acid tests acceptable, depending on institutional standards.).

Exclusion Criteria:

Pregnant or nursing women
Treatment with chemotherapy or monoclonal antibody within 28 days prior to entering the study.
Treatment with chemotherapy or monoclonal antibody during the time of participation in this trial.
Grade 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
Severe or debilitating pulmonary disease (dyspnea at rest, significant shortness of breath, COPD)
Participation in any investigational drug study within 28 days prior to ISF35 administration. (Patient must have recovered from all acute effects of previously administered investigational agents)
History of malignancy other than CLL within five years of registration, except adequately treated skin cancer.
Active symptomatic fungal, bacterial and/or viral infection including active HIV or viral (A, B or C) hepatitis.
Any illness or condition that in the opinion of the Investigator may affect safety of treatment or evaluation of any the study's endpoints.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00783874

Locations

United States, California
University of California, San Diego Moores Cancer Center
San Diego, California, United States

Sponsors and Collaborators

Memgen, LLC

University of California, San Diego

Investigators

Principal Investigator:	Januario Castro, MD	Assistant Clinical Professor in the Blood and Marrow Transplantation Division
Principal Investigator:	Thomas J Kipps, MD, PhD	Professor of Medicine, Evelyn and Edwin Tasch Chair in Cancer Research in the UCSD School of Medicine

More Information

Additional Information:

Memgen Clinical Trials This link exits the ClinicalTrials.gov site

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Responsible Party:	University of California, San Diego Moores Cancer Center ( Dr. Januario Castro, M.D./Assistant Clinical Professor in the Blood and Marrow Transplantation Division )
Study ID Numbers:	CLL-35-201
Study First Received:	October 31, 2008
Last Updated:	October 31, 2008
ClinicalTrials.gov Identifier:	NCT00783874 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Memgen, LLC:

Chronic lymphocytic leukemia
Small Lymphocytic Lymphoma
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, B-Cell
Immune System Diseases

ISF35
Ad-ISF35
CLL
SLL
non-Hodgkin's lymphoma
NHL

Study placed in the following topic categories:

Leukemia, Lymphoid
Immunoproliferative Disorders
Adenoviridae Infections
Lymphoma, Small Cleaved-cell, Diffuse
Leukemia
Lymphatic Diseases
Chronic Lymphocytic Leukemia

Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Non-Hodgkin
Leukemia, B-Cell
Lymphoproliferative Disorders
Leukemia, B-cell, Chronic
Lymphoma

Additional relevant MeSH terms:

Lymphatic Diseases
Leukemia
Neoplasms
Leukemia, Lymphoid
Immunoproliferative Disorders
Neoplasms by Histologic Type

Immune System Diseases
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoproliferative Disorders
Leukemia, B-Cell
Lymphoma

ClinicalTrials.gov processed this record on May 07, 2009