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

Trial of Immune Reconstitution With Activated T-Cells in Patients With Chronic Lymphocytic Leukemia (CLL)

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.

Study Overview

• Status: Completed
• Conditions: Anemia; Weight Loss; Thrombocytopenia; Fever; Chronic Lymphocytic Leukemia; Lymphadenopathy; Prolymphocytic Leukemia; Richter Syndrome; Cancer Fatigue; Recurrent Chronic Lymphocytic Leukemia; Lymphocytosis; Infectious Disorder; Night Sweats; Secondary Malignant Neoplasm
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Biological: Ex Vivo-activated Autologous Lymph Node Lymphocytes

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment (ex vivo autologous lymph node lymphocytes); Patients receive infusion of ex vivo-activated autologous lymph node lymphocytes IV over 10-30 minutes on day 0.	Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Ex Vivo-activated Autologous Lymph Node Lymphocytes; Given IV; Other Names: X-ACT; X-ACT Autologous Lymph Node Lymphocytes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Success and Feasibility of Autologous Activated T-cells Infusion, Determined by Number of Participants That Achieved Target-Activated T-cell Dose Without DLT.	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.	Enrollment up to day 100 post T cell infusion for each arm.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune Reconstitution	To study immune reconstitution following infusion of activated T-cells in patients with chronic lymphocytic leukemia	Up to 1 year
Overall Response Rates	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.	Up to 1 year
Incidence of Infections	To study the incidence of infections for up to 1 year following activated T cell infusion	Up to 1 year

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

Helpful Links

• MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 18, 2015
• Primary Completion (ACTUAL): April 30, 2018
• Study Completion (ACTUAL): April 30, 2018

Study Registration Dates

• First Submitted: August 19, 2015
• First Submitted That Met QC Criteria: August 19, 2015
• First Posted (ESTIMATE): August 21, 2015

Study Record Updates

• Last Update Posted (ACTUAL): October 29, 2019
• Last Update Submitted That Met QC Criteria: October 7, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Hematologic Diseases; Body Weight; Body Weight Changes; Blood Platelet Disorders; Leukocyte Disorders; Leukemia, B-Cell; Leukocytosis; Infections; Communicable Diseases; Leukemia; Weight Loss; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Thrombocytopenia; Lymphadenopathy; Leukemia, Prolymphocytic; Lymphocytosis
• Other Study ID Numbers: 2014-0830 (OTHER: M D Anderson Cancer Center); P30CA016672 (U.S. NIH Grant/Contract); NCI-2015-01546 (REGISTRY: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No