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Chronic Lymphocytic LeukemiaPhase 1NCT00772486

A Phase Ib Study of ISF35 in Combination With Chemotherapy (FCR) in Subjects With Relapsed, Refractory, and/or 17p- CLL

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
Search all trials

Trial summary

The study is a Phase 1b open label, non-randomized, single institution clinical trial that is designed to evaluate the safety and tolerability of three repeat infusions of ISF35 followed by a standard regimen of three cycles of fludarabine, cyclophosphamide and rituximab (FCR) in subjects with refractory, resistant… 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
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
1 siteUnited States
Study dates
Sep 2008to Apr 2013
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 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
  • Measurable disease, and at least one of the IWCLL 2008 Guidelines "Indications for Treatment" as follows:
  • Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia.
  • Massive (i.e., >6 cm below the left costal margin) or progressive or asymptomatic splenomegaly.
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  • Massive nodes (i.e., >10 cm in longest diameter) or progressive or symptomatic lymphadenopathy.
  • Progressive lymphocytosis with an increase of >50% over a 2-month period, or lymphocyte doubling time (LDT) of less than 6 months. LDT can be obtained by linear regression extrapolation of absolute lymphocyte counts (ALC) obtained at intervals of two weeks over an observation period of 2-3 months; patients with initial blood lymphocyte counts of less than 30,000 per microliter may require a longer observation period to determine the LDT. Also, factors contributing to lymphocytosis or lymphadenopathy other than CLL (e.g, infections) should be excluded.
  • Autoimmune anemia and/or thrombocytopenia poorly responsive to corticosteroids or other standard therapy.
  • A minimum of any one of the following disease-related symptoms must be present:
  • Unintentional weight loss ≥10% within the previous 6 months.
  • Significant fatigue (i.e., ECOG PS 2 or worse; cannot work or unable to perform usual activities).
  • Fevers of greater than 100.5 degrees F or 38.0 degrees C for 2 or more weeks without other evidence of infection.
  • Night sweats for more than 1 month without evidence of infection. Hypogammaglobulinemia or monoclonal or oligoclonal paraproteinemia does not by itself constitute a basis to initiate treatment.
  • Subjects must have CLL that is documented to be resistant or refractory to standard chemotherapy regimens containing alkylating agents and/or purine analogues. Chemotherapy refractory or resistant is defined as the following:
  • CLL progression during treatment (2 cycles) with chemotherapy; OR
  • Failure to achieve a PR or CR after at least 2 cycles of chemotherapy; OR
  • No response to treatment or stable disease after at least 2 cycles of chemotherapy; OR
  • Disease progression within 6 months of treatment with chemotherapy; OR
  • CLL with cytogenetic changes documenting the loss of the short arm of chromosome 17 (17p-) associated with the loss of p53.
  • Subjects must be age 18 years or older
  • For men and women of child-bearing potential, use of effective barrier contraceptive methods during the study and for one month following treatment
  • Subjects must have ECOG performance scale of ≤ 2
  • Subjects must have adequate hematologic, renal, hepatic, and coagulation function defined as:
  • Adequate hematologic function:
  • Platelet count ≥ 50,000/µL; AND
  • Hemoglobin ≥ 10 g/dL (may be supported by erythropoietin or transfusion); AND
  • Adequate renal function:
  • Calculated creatinine clearance ≥ 30 mL/min/1.73 m^2; OR
  • Serum creatinine ≤ 2 times upper limit of normal; AND
  • 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) ≤ 1.5; AND
  • Partial thromboplastin time ≤ 1.5 times upper limit of normal
  • 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

Who cannot join

  • Presence of > 55% prolymphocytes or Richter's transformation
  • 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
  • Untreated autoimmune hemolytic anemia or immune thrombocytopenia
  • Active symptomatic fungal, bacterial and/or viral infection including active HIV or viral (A, B or C) hepatitis
  • Positive serologies for HIV1,2 or HTLV I,II
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  • CMV disease with positive DNA PCR
  • Syphilis with positive VDRL
  • Acute Hepatitis A and C with positive serologies, and Hepatitis B, acutely or chronically infected based on CDC criteria
  • Any illness or condition that in opinion of the investigator may affect safety of treatment or evaluation of any study's endpoints

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of California, San Diego Moores Cancer Center

    San Diego, California, 92093

Other trials in United States

About this study

Official title: A Phase 1b Study of Repeated Doses of Autologous CLL B Cells Transduced to Express Chimeric CD154 (ISF35) in Combination With Fludarabine, Cyclophosphamide and Rituximab (FCR) in Subjects With Chronic Lymphocytic Leukemia (CLL)

The study is a Phase 1b open label, non-randomized, single institution clinical trial that is designed to evaluate the safety and tolerability of three repeat infusions of ISF35 followed by a standard regimen of three cycles of fludarabine, cyclophosphamide and rituximab (FCR) in subjects with refractory, resistant, and/or 17p- CLL.

Read the detailed description

ISF35 has already been used in two 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.

The trials also showed that ISF35 stimulates the immune system to act against CLL cells and sensitize leukemic cells to subsequent treatment. Repeat infusions of ISF35 administered as a single agent to subjects with CLL resulted in durable reductions in circulating and lymph-node bound leukemic cells. Furthermore, CLL patients with 17p deletion responded to standard courses of FCR after receiving ISF35 and achieved durable remissions.

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.

Being tested
ISF35
Keywords
Chronic lymphocytic leukemia, Leukemia, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, B-Cell, Immune System Diseases, Rituximab, Fludarabine, Cyclophosphamide, ISF35, Ad-ISF35, Refractory, Resistant, 17p-, del 17p, 17p, Resistant CLL, Refractory CLL, 17p- CLL, CLL
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Leukemia, B-Cell, Immune System Diseases, Chromosome 17 deletion

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 course of three infusions of 3x10^8 ISF35-transduced cells at periods of not less than 14 days apart followed by a standard regimen of three cycles of fludarabine, cyclophosphamide and rituximab (FCR) at monthly intervals.

Study groups in NCT00772486
Study groupRoleWhat they receive
Experimental: ISF35 and FCRExperimentalISF35 and FCR
Receives: Biological: ISF35

What is being measured

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

  1. Assess toxicity, tolerability, and safety of repeat administration of three infusions of 3x10^8 ISF35 given intravenously in combination with a standard course of three treatments of fludarabine, rituximab and cyclophosphamide (FCR).

    Measured: Duration of the Trial

Secondary outcomes (2)

  1. Explore the anti-leukemia activity of the repeat administration of ISF35 and FCR by evaluating reduction in leukemia count, reduction in lymphadenopathy and splenomegaly, improvement in bone marrow function, and response duration.

    Measured: Duration of the Trial

  2. Assess induction of B and T cell anti-leukemia immune responses, antibody production against autologous CLL B cells, changes in bystander leukemia cell phenotype, and expression of genes and proteins related to apoptosis

    Measured: Duration of the Trial

Timeline

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

  1. First posted15 Oct 2008 (estimated)
  2. Study startSep 2008
  3. Primary completionApr 2011
  4. Study completionApr 2013

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00772486
Sponsor's protocol ID
CLL-35-104
Status last verified
Nov 2010
First submitted
14 Oct 2008
Last updated
22 Sep 2021
Results posted
No
Data monitoring committee
Yes

Publications

  • Keating MJ, O'Brien S, Albitar M, Lerner S, Plunkett W, Giles F, Andreeff M, Cortes J, Faderl S, Thomas D, Koller C, Wierda W, Detry MA, Lynn A, Kantarjian H. Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. J Clin Oncol. 2005 Jun 20;23(18):4079-88. doi: 10.1200/JCO.2005.12.051. Epub 2005 Mar 14.

    PubMed 15767648

  • Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Dohner H, Hillmen P, Keating MJ, Montserrat E, Rai KR, Kipps TJ; International Workshop on Chronic Lymphocytic Leukemia. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008 Jun 15;111(12):5446-56. doi: 10.1182/blood-2007-06-093906. Epub 2008 Jan 23.

    PubMed 18216293

  • Rai KR. Characteristics and Management of Chronic Lymphocytic Leukemia. Advances in Oncology. 1996;9 No.1:17-20.

  • Kalil N, Cheson BD. Chronic lymphocytic leukemia. Oncologist. 1999;4(5):352-69.

    PubMed 10551552

  • Kay NE, Hamblin TJ, Jelinek DF, Dewald GW, Byrd JC, Farag S, Lucas M, Lin T. Chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program. 2002:193-213. doi: 10.1182/asheducation-2002.1.193.

    PubMed 12446424

  • Bosch F, Montserrat E. Refining prognostic factors in chronic lymphocytic leukemia. Rev Clin Exp Hematol. 2002 Dec;6(4):335-49; discussion 449-50. doi: 10.1046/j.1468-0734.2002.00302.x. No abstract available.

    PubMed 12823776

  • Byrd JC, Waselenko JK, Keating M, Rai K, Grever MR. Novel therapies for chronic lymphocytic leukemia in the 21st century. Semin Oncol. 2000 Oct;27(5):587-97.

    PubMed 11049025

  • Nabhan C, Gartenhaus RB, Tallman MS. Purine nucleoside analogues and combination therapies in B-cell chronic lymphocytic leukemia: dawn of a new era. Leuk Res. 2004 May;28(5):429-42. doi: 10.1016/j.leukres.2003.08.017.

    PubMed 15068894

  • Nabhan C, Dyer MJ, Rosen ST. Current status of monoclonal antibody therapy for chronic lymphocytic leukemia. Oncology (Williston Park). 2003 Feb;17(2):253-62; discussion 264, 267, passim.

    PubMed 12632866

  • Byrd JC, Stilgenbauer S, Flinn IW. Chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program. 2004:163-83. doi: 10.1182/asheducation-2004.1.163.

    PubMed 15561682

  • Rozman C, Montserrat E. Chronic lymphocytic leukemia. N Engl J Med. 1995 Oct 19;333(16):1052-7. doi: 10.1056/NEJM199510193331606. No abstract available.

    PubMed 7675049

  • Ghia P, Caligaris-Cappio F. The origin of B-cell chronic lymphocytic leukemia. Semin Oncol. 2006 Apr;33(2):150-6. doi: 10.1053/j.seminoncol.2006.01.009.

    PubMed 16616061

  • Chiorazzi N, Rai KR, Ferrarini M. Chronic lymphocytic leukemia. N Engl J Med. 2005 Feb 24;352(8):804-15. doi: 10.1056/NEJMra041720. No abstract available.

    PubMed 15728813

  • Perz J, Topaly J, Fruehauf S, Hensel M, Ho AD. Level of CD 20-expression and efficacy of rituximab treatment in patients with resistant or relapsing B-cell prolymphocytic leukemia and B-cell chronic lymphocytic leukemia. Leuk Lymphoma. 2002 Jan;43(1):149-51. doi: 10.1080/10428190210178.

    PubMed 11908720

  • Cheson BD, Bennett JM, Rai KR, Grever MR, Kay NE, Schiffer CA, Oken MM, Keating MJ, Boldt DH, Kempin SJ, et al. Guidelines for clinical protocols for chronic lymphocytic leukemia: recommendations of the National Cancer Institute-sponsored working group. Am J Hematol. 1988 Nov;29(3):152-63. doi: 10.1002/ajh.2830290307.

    PubMed 3189311

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 37 inclusion and 10 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 22 Sep 2021. 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 toxicity, tolerability, and safety of repeat administration of three infusions of 3x10^8 ISF35 given intravenously in combination with a standard course of three treatments of fludarabine, rituximab and cyclophosphamide (FCR). (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 NCT00772486, which also lists 25 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 22 Sep 2021.

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