Study of Repeat Intranodal Injection of Memgen's Cancer Vaccine, Ad-ISF35, in Subjects With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

• Sponsor: Januario Castro, M.D. (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00849524
• Collaborator: FDA Office of Orphan Products Development (U.S. Fed), Memgen, LLC (Industry)
• Enrollment: 6
• Location: 1
• Arm: 1
• Duration (Months): 65.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a Phase II, open label, fixed dose, repeat injection, single institution study. Eligible subjects will receive up to six doses of Ad-ISF35 injected directly into a selected lymph node under ultrasound guidance. The primary goal is to determine and monitor clinical and biological responses in patients treated with repeat intranodal injections of Ad-ISF35.

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma	Biological: ISF35	Phase 2

Detailed Description

This is a phase II clinical trial in which study subjects will be treated with multiple doses of Ad-ISF35 given via intranodal injection using a fixed dose of 3.3 x 10^10 ISF35 viral particles. Intranodal injections will be administered every 2-4 weeks up to six total injections.

Because this is the first time that repeat administration of Ad-ISF35 will be performed via intranodal injection, and in order to allow sufficient time to evaluate the safety and toxicity of this procedure, we will treat subjects 1 thru 3 at one month intervals and with inpatient admission for 24 hours observation. After subject three receives their second ISF35 injection we will proceed with enrollment of cohorts of four patients per month at one week intervals until study enrollment has been completed. These subjects will be treated as outpatients and will be observed for 3 hours prior to discharge.

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Repeat Intranodal Injections of Adenovirus-CD 154 (Ad-ISF35) in Patients With Chronic Lymphocytic Leukemia/ Small Lymphocytic Lymphoma
• Study Start Date: Jan 1, 2009
• Actual Primary Completion Date: Jul 1, 2009
• Actual Study Completion Date: Jul 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ad-ISF35 Ad-ISF35, intranodal injection, 3.3 x 10^10 ISF35 viral particles, every 2-4 weeks up to six total injections.	Biological: ISF35; Subjects participating in this study will be treated with multiple doses of Ad-ISF35 given via intranodal injection using a fixed dose of 3.3 x 10^10 ISF35 viral particles. Intranodal injections will be administered every 2-4 weeks up to six total injections.

Outcome Measures

Primary Outcome Measures

1. Determine and Monitor Clinical and Biological Responses in Patients Treated With Repeat Intranodal Injections of Ad-ISF35. [2 years (evaluation will be approx. 4 months per patient)]

Secondary Outcome Measures

1. Determine the Safety of Repeat Administration of Ad-ISF35 Injected Directly Into Lymph Nodes of Patients With CLL/SLL. [2 years (evaluation will be approx. 1 year per patient)]

2. Determine Pharmacodynamic Parameters in Patients Treated With Repeat Intranodal Injections of Ad-ISF35. [2 years (evaluation will be approx. 4 months per patient)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. 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.

1. 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.

2. Intermediate or High risk, poor prognosis CLL/SLL

3. Indication for treatment as defined by the NCI Working Group Guidelines:

• Massive (> 6 cm below the left costal margin) or progressive splenomegaly OR

• Massive lymph nodes or nodal clusters (> 10 cm in longest diameter) OR *Progressive lymphadenopathy OR

• Grade 2 or 3 fatigue OR

• Fever ≥ 100.5 degrees 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.

1. Males and females 18 years of age and older

2. Laboratory parameters as specified below:

• Hematologic: Hemoglobin ≥ 10 g/dL (may be post-transfusion); platelet count ≥ 50x10^3/mm3

• Hepatic: Total Bilirubin < 2 x ULN, and ALT and AST < 2 x ULN

• Renal: Creatinine ≤ 2 x ULN

1. ECOG Performance Status ≤ 2

2. Anticipated survival of at least 3 months

3. For men and women of child-producing potential, use of effective barrier contraceptive methods during the study and for one month following treatment.

4. 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.

5. Negative test results for current/active infection with HIV-1, HIV-2, HTLV-1, HTLV-2, CMV, hepatitis A, B, C within 30 days of registration. (Antibody, antigen and nucleic acid tests acceptable, depending on institutional standards.).

6. Subjects must give written informed consent to participate in this trial.

7. Subjects must have received treatment for CLL with chemotherapy agents or antibodies OR if subjects are previously untreated they must state in the consent form that they are refusing to be treated with chemotherapy or antibodies.

Exclusion Criteria:

1. Pregnant or nursing women.

2. Treatment with chemotherapy or monoclonal antibody within 28 days prior to entering the study.

3. Treatment with chemotherapy or monoclonal antibody during the time of participation in this trial.

4. Grade 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification.

5. Severe or debilitating pulmonary disease (dyspnea at rest, significant shortness of breath, COPD).

6. 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)

7. History of malignancy other than CLL within five years of registration, except patients with adequately treated basal, squamous cell carcinoma or localized cervical cancer.

8. Active symptomatic fungal, bacterial and/or viral infection including active HIV or viral (A, B or C) hepatitis.

9. 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

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Diego Moores Cancer Center	La Jolla	California	United States	92093

Sponsors and Collaborators

• Januario Castro, M.D.
• FDA Office of Orphan Products Development
• Memgen, LLC

Investigators

• Principal Investigator: Januario Castro, M.D., Associate Clinical Professor in the Blood and Marrow Transplantation Division
• Principal Investigator: Thomas J Kipps, M.D., Ph.D., Professor of Medicine, Evelyn and Edwin Tasch Chair in Cancer Research in the UCSD School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Januario Castro, M.D., Assistant Clinical Professor, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT00849524
• Other Study ID Numbers: UCSD-101357 - prev 080497; CLL-35-202
• First Posted: Feb 24, 2009
• Last Update Posted: Dec 30, 2015
• Last Verified: Nov 1, 2015

• Additional relevant MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell

Study Results

Participant Flow

Arm/Group Title	Ad-ISF35
Arm/Group Description	Ad-ISF35, intranodal injection, 3.3 x 10^10 ISF35 viral particles, every 2-4 weeks up to six total injections. ISF35: Subjects participating in this study will be treated with multiple doses of Ad-ISF35 given via intranodal injection using a fixed dose of 3.3 x 10^10 ISF35 viral particles. Intranodal injections will be administered every 2-4 weeks up to six total injections.
Period Title: Overall Study
STARTED	6
COMPLETED	3
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Ad-ISF35
Arm/Group Description	Ad-ISF35, intranodal injection, 3.3 x 10^10 ISF35 viral particles, every 2-4 weeks up to six total injections. ISF35: Subjects participating in this study will be treated with multiple doses of Ad-ISF35 given via intranodal injection using a fixed dose of 3.3 x 10^10 ISF35 viral particles. Intranodal injections will be administered every 2-4 weeks up to six total injections.
Overall Participants	6
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 33.3%
>=65 years	4 66.7%
Sex: Female, Male (Count of Participants)
Female	1 16.7%
Male	5 83.3%
Region of Enrollment (participants) [Number]
United States	6 100%

Outcome Measures

1. Primary Outcome

Title	Determine and Monitor Clinical and Biological Responses in Patients Treated With Repeat Intranodal Injections of Ad-ISF35.
Time Frame	2 years (evaluation will be approx. 4 months per patient)

Outcome Measure Data

Analysis Population Description

The study was not completed due to unavailability of the study drug, and therefore data were not collected for this Outcome Measure.

Arm/Group Title	Ad-ISF35
Arm/Group Description	Ad-ISF35, intranodal injection, 3.3 x 10^10 ISF35 viral particles, every 2-4 weeks up to six total injections. ISF35: Subjects participating in this study will be treated with multiple doses of Ad-ISF35 given via intranodal injection using a fixed dose of 3.3 x 10^10 ISF35 viral particles. Intranodal injections will be administered every 2-4 weeks up to six total injections.
Measure Participants	0

2. Secondary Outcome

Title	Determine the Safety of Repeat Administration of Ad-ISF35 Injected Directly Into Lymph Nodes of Patients With CLL/SLL.
Time Frame	2 years (evaluation will be approx. 1 year per patient)

Outcome Measure Data

Analysis Population Description

The study was not completed due to unavailability of the study drug, and therefore data were not collected for this Outcome Measure.

Arm/Group Title	Ad-ISF35
Arm/Group Description	Ad-ISF35, intranodal injection, 3.3 x 10^10 ISF35 viral particles, every 2-4 weeks up to six total injections. ISF35: Subjects participating in this study will be treated with multiple doses of Ad-ISF35 given via intranodal injection using a fixed dose of 3.3 x 10^10 ISF35 viral particles. Intranodal injections will be administered every 2-4 weeks up to six total injections.
Measure Participants	0

3. Secondary Outcome

Title	Determine Pharmacodynamic Parameters in Patients Treated With Repeat Intranodal Injections of Ad-ISF35.
Time Frame	2 years (evaluation will be approx. 4 months per patient)

Outcome Measure Data

Analysis Population Description

The study was not completed due to unavailability of the study drug, and therefore data were not collected for this Outcome Measure.

Arm/Group Title	Ad-ISF35
Arm/Group Description	Ad-ISF35, intranodal injection, 3.3 x 10^10 ISF35 viral particles, every 2-4 weeks up to six total injections. ISF35: Subjects participating in this study will be treated with multiple doses of Ad-ISF35 given via intranodal injection using a fixed dose of 3.3 x 10^10 ISF35 viral particles. Intranodal injections will be administered every 2-4 weeks up to six total injections.
Measure Participants	0

Adverse Events

Arm/Group Title	Ad-ISF35
Arm/Group Description	Ad-ISF35, intranodal injection, 3.3 x 10^10 ISF35 viral particles, every 2-4 weeks up to six total injections. ISF35: Subjects participating in this study will be treated with multiple doses of Ad-ISF35 given via intranodal injection using a fixed dose of 3.3 x 10^10 ISF35 viral particles. Intranodal injections will be administered every 2-4 weeks up to six total injections.
All Cause Mortality
	Ad-ISF35
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ad-ISF35
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Other (Not Including Serious) Adverse Events
	Ad-ISF35
	Affected / at Risk (%)	# Events
Total	6/6 (100%)
Gastrointestinal disorders
Vomiting	2/6 (33.3%)
Nausea	4/6 (66.7%)
Constipation	1/6 (16.7%)
General disorders
Hyponatremia	1/6 (16.7%)
Fever	6/6 (100%)
Sweating	6/6 (100%)
Fatigue	6/6 (100%)
Anorexia	3/6 (50%)
Immune system disorders
Flu like syndrome	6/6 (100%)
Injection site reaction	6/6 (100%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Arthritis (non-septic)	3/6 (50%)
Renal and urinary disorders
Urinary frequency	2/6 (33.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnea-Shortness of breath	2/6 (33.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.