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Ex Vivo-activated Autologous Lymph Node Lymphocytes in Treating Patients With Chronic Lymphocytic Leukemia

Phase 2
Completed
Conditions
Infectious Disorder
Recurrent Chronic Lymphocytic Leukemia
Cancer Fatigue
Chronic Lymphocytic Leukemia
Thrombocytopenia
Weight Loss
Anemia
Fever
Lymphadenopathy
Lymphocytosis
Interventions
Biological: Ex Vivo-activated Autologous Lymph Node Lymphocytes
Other: Laboratory Biomarker Analysis
Registration Number
NCT02530515
Lead Sponsor
M.D. Anderson Cancer Center
Brief Summary

This phase II trial studies the side effects of ex vivo-activated autologous lymph node lymphocytes infusion and to see how well they work in treating patients with chronic lymphocytic leukemia. Biological therapies, such as ex vivo-activated autologous lymph node lymphocytes, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop tumor cells from growing.

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the feasibility and safety of infusion of autologous activated T-cells (ex vivo-activated autologous lymph node lymphocytes) in patients with chronic lymphocytic leukemia.

SECONDARY OBJECTIVES:

I. To study immune reconstitution following infusion of activated T-cells in patients with chronic lymphocytic leukemia.

II. To study the incidence of infections for up to 1 year following activated T cell infusion.

III. To study the overall response rates.

OUTLINE:

Patients receive infusion of ex vivo-activated autologous lymph node lymphocytes intravenously (IV) over 10-30 minutes on day 0.

Patients who have been previously treated on study, and subsequently need additional infusions, may be retreated with previously cryopreserved expanded cells at the same or lower dose level 6-12 months after the first infusion.

After completion of study treatment, patients are followed up at 1.5 years and then every 6 months for up to 5 years.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
8
Inclusion Criteria
  • All patients must have a diagnosis of chronic lymphocytic leukemia (CLL) by immunophenotyping and flow cytometry analysis of blood or bone marrow

    • Patients must meet criteria for treatment based on the criteria proposed by National Cancer Institute (NCI)-sponsored CLL Working Group to include at least one of the following:

      • Weight loss of more than 10% over the preceding 6 months; or
      • Extreme fatigue attributable to progressive disease; or
      • Fever or night sweats without evidence of infection; or
      • Worsening anemia (Rai stage Ill) or thrombocytopenia (Rai stage IV); or
      • Massive lymphadenopathy (> 10 cm) or rapidly progressive lymphocytosis (lymphocyte doubling time < 6 months); or
      • Prolymphocytic or Richter's transformation; or
    • Patients with CLL who have received at least one prior line of therapy; or

    • Patients with CLL who have frequent infections and/or recurrent secondary cancers

  • No active central nervous system (CNS) disease

  • All patients must have a Karnofsky performance score > 60%

  • Calculated creatinine clearance (by Cockcroft-Gault) of > 50 ml/min

  • Patients must not have untreated or uncontrolled life-threatening infection

  • Patients must sign informed consent

Exclusion Criteria
  • Receipt of glucocorticoids (with the exception of inhaled glucocorticoid steroids for the use of allergic rhinitis or pulmonary disease) within 2 weeks of registration
  • Autoimmune disease related to CLL, e.g., idiopathic thrombocytopenic purpura (ITP) or autoimmune hemolytic anemia, is permitted if not requiring active treatment

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Treatment (ex vivo autologous lymph node lymphocytes)Laboratory Biomarker AnalysisPatients receive infusion of ex vivo-activated autologous lymph node lymphocytes IV over 10-30 minutes on day 0.
Treatment (ex vivo autologous lymph node lymphocytes)Ex Vivo-activated Autologous Lymph Node LymphocytesPatients receive infusion of ex vivo-activated autologous lymph node lymphocytes IV over 10-30 minutes on day 0.
Primary Outcome Measures
NameTimeMethod
Treatment Success and Feasibility of Autologous Activated T-cells Infusion, Determined by Number of Participants That Achieved Target-Activated T-cell Dose Without DLT.Enrollment up to day 100 post T cell infusion for each arm.

Success will be defined as achievement of a target activated T-cell dose of 1x108 +/-20% without DLT and the lack of dose limiting toxicity (DLT). DLT for this trial is defined as any Grade 4 or higher non-hematologic toxicity or grade 3 or 4 allergy/immunology toxicity, allergic reaction or urticaria grade 3 or higher by +90 days after T cell infusion, Grade 2 or greater autoimmune phenomena, or Grade 4 or higher hematologic toxicity (with the exception of any preexisting AE due to prior treatment or due to disease) deemed related to T cells and occurring by day +90 after T cell infusion. Feasibility is defined as achievement of the target T-cell dose (1x108 +/-20% ) without DLT in \>50% of patients enrolled.

Secondary Outcome Measures
NameTimeMethod
Incidence of InfectionsUp to 1 year

To study the incidence of infections for up to 1 year following activated T cell infusion

Immune ReconstitutionUp to 1 year

To study immune reconstitution following infusion of activated T-cells in patients with chronic lymphocytic leukemia

Overall Response RatesUp to 1 year

The overall response rates between the lenalidomide and non-lenalidomide arms. For response to treatment, it was measured by International Workshop on CLL (iwCLL), criteria 2008 guidelines.

Trial Locations

Locations (1)

M D Anderson Cancer Center

🇺🇸

Houston, Texas, United States

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