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Chronic Lymphocytic LeukemiaPhase 1NCT00779883

A Phase I Trial of Autologous CLL B Cells Transduced to Express Chimeric CD154 (ISF35)

A Phase 1 study testing ISF35 in people with Chronic Lymphocytic Leukemia, run by Memgen, LLC at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The study is a Phase I, dose-escalating, non-randomized, single institution clinical trial assessing the safety and efficacy of autologous Ad-ISF35-transduced CLL B cells administered as a single intravenous infusion in patients with chronic lymphocytic leukemia (CLL). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Lymphocytic Leukemia
What is being tested?
ISF35
How many people
9 participants
Where
1 siteUnited States
Study dates
Jun 2006to Mar 2008
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects must have a diagnosis of B cell CLL, measurable disease, and an
  • NCI-WG indication for treatment with one of the following:
  • Massive (>6 cm below left costal margin) or progressive splenomegaly;
  • Massive (>10 cm longest diameter) lymph nodes, nodal clusters, or progressive lymphadenopathy;
  • Progressive anemia;
  • Progressive thrombocytopenia;
Show all 27Show fewer
  • Weight loss > 10% body weight over the preceding 6 month period;
  • Fatigue attributable to CLL;
  • Fever or night sweats without evidence of infection;
  • Progressive lymphocytosis.
  • Subjects must be age 18 years or older.
  • Women of childbearing potential (not postmenopausal for at least one year or not surgically incapable of bearing children) must agree not to become pregnant for the duration of the study. Both men and women participants must agree to use contraception for the duration of the study.
  • Subjects must have Zubrod performance status of ≤ 2 (Appendix B).
  • Subjects must have adequate hematologic, renal, hepatic, and coagulation function:
  • Adequate hematologic function:
  • Platelet count ≥ 50,000/μl; AND
  • Hemoglobin ≥ 10 g/dl (may be supported by erythropoietin or transfusion).
  • Adequate renal function:
  • Serum creatinine ≤ 1.5 times upper limit of normal; OR
  • Measured creatinine clearance ≥ 40 mL/min/1.73 m^2.
  • Adequate hepatic function:
  • Total bilirubin ≤ 2.5 times upper limit of normal; AND
  • ALT ≤ 2.5 times upper limit of normal; AND
  • Adequate coagulation tests:
  • Prothrombin time international normalized ratio (INR) ≤ 2; AND
  • Partial thromboplastin time ≤ 1.66 times upper limit of normal
  • Subjects must be able to give written informed consent.

Who cannot join

  • Presence of more than 55% prolymphocytes.
  • Chemotherapy (e.g., purine analogues, alkylating agents, or corticosteroids), antibody therapy, immunotherapy, radiation therapy, or participation in any investigational drug treatment within 4 weeks of enrollment into protocol or at any time during the study.
  • Ongoing toxicity from prior anti-neoplastic therapy.
  • Prior gene therapy or allogeneic stem cell transplantation.
  • Untreated autoimmune hemolytic anemia or immune thrombocytopenia.
  • Active infection requiring parenteral antibiotics.
  • Known HIV/HBV/HCV seropositivity.
  • Uncompensated hypothyroidism (defined as TSH greater than 4x upper limit of normal not treated with replacement hormone).

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Texas M.D. Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

The study is a Phase I, dose-escalating, non-randomized, single institution clinical trial assessing the safety and efficacy of autologous Ad-ISF35-transduced CLL B cells administered as a single intravenous infusion in patients with chronic lymphocytic leukemia (CLL).

Read the detailed description

Memgen's first TNF family derived product, ISF35, is a gene that encodes a recombinant protein molecule that binds and activates human CD40+ B lymphocytes that are found on a vast majority of malignant leukemias and lymphomas.

In this clinical trial, ISF35 will be introduced into the patients' CLL cells ex vivo using a replication-defective adenovirus Ad5 encoding the ISF35 cDNA transgene. After this ex vivo manipulation, the modified leukemia cells will be extensively washed and the amount of remaining free virus is measured before the cells are reinfused into the patient. Following ex vivo transduction, the CLL cells expressing ISF35 activate a therapeutic immune response directed against the target leukemia cells.

This ascending-dose trial will be divided into three dosing cohorts to determine the existence of a maximum tolerated dose.

Patients will be followed for 12 months after ISF35 administration or until initiation of another treatment.

Being tested
ISF35
Keywords
Chronic lymphocytic leukemia, CLL, Leukemia, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, B-Cell, Immune System Diseases, ISF35, Ad-ISF35, Immunotherapy, Immune therapy, Active immune therapy
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Leukemia, B-Cell, Immune System Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ISF35Biological

    Also called Ad-ISF35, AdISF35

    Subjects participating in this study will receive a single dose of 1x10^8, 3x10^8, or 1x10^9 autologous Ad-ISF35-transduced CLL B cells.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Assess the toxicity, tolerability, and safety of 1x10^8, 3x10^8, and 1x10^9 autologous Ad-ISF35-transduced CLL B cells given as a single intravenous infusion in patients with CLL.

    Measured: Duration of the trial

Secondary outcomes (3)

  1. Assess the anti-leukemia activity of a single intravenous dose by evaluating reduction in leukemia count, reduction in adenopathy and splenomegaly, and improvement in bone function.

    Measured: Duration of the trial

  2. Assess the quality of life with ISF35 treatment.

    Measured: Two months

  3. Assess pharmacodynamic endpoints including induction of T cell anti-leukemia immune responses, antibody production against autologous CLL B cells, and changes in bystander leukemia cell phenotype.

    Measured: Two months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Oct 2008 (estimated)
  2. Study startJun 2006
  3. Primary completionMar 2008
  4. Study completionMar 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00779883
Sponsor's protocol ID
CLL-35-101
Status last verified
Oct 2008
First submitted
23 Oct 2008
Last updated
24 Oct 2008
Results posted
No
Data monitoring committee
Yes

Publications

  • Aguilar-Santelises M, Rottenberg ME, Lewin N, Mellstedt H, Jondal M. Bcl-2, Bax and p53 expression in B-CLL in relation to in vitro survival and clinical progression. Int J Cancer. 1996 Apr 22;69(2):114-9. doi: 10.1002/(SICI)1097-0215(19960422)69:23.0.CO;2-3.

    PubMed 8608978

  • Armitage RJ, Fanslow WC, Strockbine L, Sato TA, Clifford KN, Macduff BM, Anderson DM, Gimpel SD, Davis-Smith T, Maliszewski CR, et al. Molecular and biological characterization of a murine ligand for CD40. Nature. 1992 May 7;357(6373):80-2. doi: 10.1038/357080a0.

    PubMed 1374165

  • Bacik J, Mazumdar M, Murphy BA, Fairclough DL, Eremenco S, Mariani T, Motzer RJ, Cella D. The functional assessment of cancer therapy-BRM (FACT-BRM): a new tool for the assessment of quality of life in patients treated with biologic response modifiers. Qual Life Res. 2004 Feb;13(1):137-54. doi: 10.1023/B:QURE.0000015297.91158.01.

    PubMed 15058795

  • Banchereau J, Bazan F, Blanchard D, Briere F, Galizzi JP, van Kooten C, Liu YJ, Rousset F, Saeland S. The CD40 antigen and its ligand. Annu Rev Immunol. 1994;12:881-922. doi: 10.1146/annurev.iy.12.040194.004313.

    PubMed 7516669

  • Bosch F, Ferrer A, Lopez-Guillermo A, Gine E, Bellosillo B, Villamor N, Colomer D, Cobo F, Perales M, Esteve J, Altes A, Besalduch J, Ribera JM, Montserrat E; GELCAB (Grup per l'Estudi dels Limfomes a Catalunya i Balears). Fludarabine, cyclophosphamide and mitoxantrone in the treatment of resistant or relapsed chronic lymphocytic leukaemia. Br J Haematol. 2002 Dec;119(4):976-84. doi: 10.1046/j.1365-2141.2002.03959.x.

    PubMed 12472576

  • Caligaris-Cappio F. B-chronic lymphocytic leukemia: a malignancy of anti-self B cells. Blood. 1996 Apr 1;87(7):2615-20. No abstract available.

    PubMed 8639876

  • Cantwell MJ, Sharma S, Friedmann T, Kipps TJ. Adenovirus vector infection of chronic lymphocytic leukemia B cells. Blood. 1996 Dec 15;88(12):4676-83.

    PubMed 8977261

  • Cantwell M, Hua T, Pappas J, Kipps TJ. Acquired CD40-ligand deficiency in chronic lymphocytic leukemia. Nat Med. 1997 Sep;3(9):984-9. doi: 10.1038/nm0997-984.

    PubMed 9288724

  • Castle BE, Kishimoto K, Stearns C, Brown ML, Kehry MR. Regulation of expression of the ligand for CD40 on T helper lymphocytes. J Immunol. 1993 Aug 15;151(4):1777-88.

    PubMed 8102152

  • Castro JE, Cantwell MJ, Prusak CE, Bole J, Wierda WG, Kipps TJ. long-term followup of chronic lymphocytic leukemia patients treated with CD40-ligand (CD154) gene therapy. Blood 2003; 102(11):491a (Abstract #1790).

  • Cheson BD, Bennett JM, Grever M, Kay N, Keating MJ, O'Brien S, Rai KR. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood. 1996 Jun 15;87(12):4990-7. No abstract available.

    PubMed 8652811

  • Chu P, Deforce D, Pedersen IM, Kim Y, Kitada S, Reed JC, Kipps TJ. Latent sensitivity to Fas-mediated apoptosis after CD40 ligation may explain activity of CD154 gene therapy in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3854-9. doi: 10.1073/pnas.022604399. Epub 2002 Mar 12.

    PubMed 11891278

  • Clark EA, Ledbetter JA. How B and T cells talk to each other. Nature. 1994 Feb 3;367(6462):425-8. doi: 10.1038/367425a0.

    PubMed 8107800

  • Clavio M, Miglino M, Spriano M, Pietrasanta D, Vallebella E, Celesti L, Canepa L, Pierri I, Cavaliere M, Ballerini F, Beltrami G, Rossi E, Vimercati R, Bruni R, Congiu M, Nati S, Damasio E, Santini G, Gobbi M. First line Fludarabine treatment of symptomatic chronic lymphoproliferative diseases: clinical results and molecular analysis of minimal residual disease. Eur J Haematol. 1998 Sep;61(3):197-203. doi: 10.1111/j.1600-0609.1998.tb01084.x.

    PubMed 9753416

  • Dicker F, Kater AP, Fukuda T, Kipps TJ. Fas-ligand (CD178) and TRAIL synergistically induce apoptosis of CD40-activated chronic lymphocytic leukemia B cells. Blood. 2005 Apr 15;105(8):3193-8. doi: 10.1182/blood-2003-10-3684. Epub 2004 Aug 31.

    PubMed 15339846

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ISF35 in people with Chronic Lymphocytic Leukemia, run by Memgen, LLC at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Oct 2008. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Assess the toxicity, tolerability, and safety of 1x10^8, 3x10^8, and 1x10^9 autologous Ad-ISF35-transduced CLL B cells given as a single intravenous infusion in patients with CLL. (time frame: Duration of the trial). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00779883, which also lists 53 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2008.

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