Pharmacodynamic (PD) Study of Intranodal Adenovirus-CD154 (Ad-ISF35) in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

NCT00850057 | Completed Phase 1 DMC

• 1 other identifier: UCSD-060201
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objectives

• To determine the safety and maximum tolerated dose (MTD) of Adenovirus-CD154 (Ad-ISF35) when it is injected directly into the lymph nodes of patients with CLL or SLL. Secondary Objectives
• To determine and monitor clinical and biological responses in patients treated with injections of Ad-ISF35.
• To determine how ISF35 works in CLL/SLL patients' cells.

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (1)

• Determine the safety and maximum tolerated dose (MTD) of Adenovirus-CD154 (Ad-ISF35) when injected directly into lymph nodes of patients with CLL/SLL.

  2 years

Secondary Outcomes (2)

• Determine and monitor clinical and biological responses in patients treated with intranodal injections of Ad-ISF35.

  2 years

• Determine pharmacodynamic (PD) parameters in patients treated with intranodal injections of ISF35.

  2 years

Interventions

Intranodal injection of Ad-ISF35 BIOLOGICAL

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 cervical, 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 (i.e. \> 6 cm below the left costal margin) or progressive splenomegaly OR
• Massive lymph nodes or nodal clusters (i.e. \> 10 cm in longest diameter), 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 6 months.
• Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and / or thrombocytopenia.
• Autoimmune anemia and / or thrombocytopenia poorly responsive to corticosteroid therapy.
• Males and females 18 years of age and older

You may not qualify if:

• 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 patients with adequately treated basal, squamous cell carcinoma or localized cervical 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.

Sponsors & Collaborators

• University of California, San Diego: lead
• Memgen, LLC: collaborator

Study Sites (1)

University of California, San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Januario Castro, M.D.

  Assistant Clinical Professor in the Blood and Marrow Transplantation Division

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2009
• First Posted: February 24, 2009
• Study Start: February 1, 2006
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: July 12, 2019

Record last verified: 2019-07

Locations

US (1)