Anemia, Cancer Fatigue, Chronic Lymphocytic Leukemia, Fever, Infectious Disorder, Lymphadenopathy, Lymphocytosis, Night Sweats, Prolymphocytic Leukemia, Recurrent Chronic Lymphocytic Leukemia, Richter Syndrome, Secondary Malignant Neoplasm, Thrombocytopenia, Weight Loss
Conditions
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.
Interventions
BIOLOGICALEx Vivo-activated Autologous Lymph Node Lymphocytes
Given IV
OTHERLaboratory Biomarker Analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Immune Reconstitution | Up to 1 year | To study immune reconstitution following infusion of activated T-cells in patients with chronic lymphocytic leukemia |
| Overall Response Rates | Up 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. |
| Incidence of Infections | Up to 1 year | To study the incidence of infections for up to 1 year following activated T cell infusion |
Countries
United States
Participant flow
Pre-assignment details
Patients who qualify for lymphodepleting chemotherapy and who do not have 17p deletion are randomized to Arm A or Arm B. Those patients who do not qualify by those criteria are assigned to Arm C.
Participants by arm
| Arm | Count |
|---|---|
| Arm A Receive lymphodepletion chemotherapy followed by activated T-cell infusion | 0 |
| Arm B Receive lymphodepletion chemotherapy followed by activated T-cell infusion followed by low dose lenalidomide PO once ANC is\>1.5x109/L | 0 |
| Arm C Patients who cannot receive lymphodepleting chemotherapy (as determined by the treating physician) or those with 17p deletion | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Arm A | Arm B | Arm C | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 7 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Age, Continuous | — | — | 74.5 years | 74.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 7 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 7 Participants | 7 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 4 Participants | 4 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 4 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 | 0 / 8 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 8 / 8 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 8 |
Outcome results
Primary
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.
Time frame: Enrollment up to day 100 post T cell infusion for each arm.
Population: Patients with CLL.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm C | Treatment Success and Feasibility of Autologous Activated T-cells Infusion, Determined by Number of Participants That Achieved Target-Activated T-cell Dose Without DLT. | Sucessful Target T-cell Dose | 7 Participants |
| Arm C | Treatment Success and Feasibility of Autologous Activated T-cells Infusion, Determined by Number of Participants That Achieved Target-Activated T-cell Dose Without DLT. | Feasibility | 7 Participants |
Secondary
Immune Reconstitution
To study immune reconstitution following infusion of activated T-cells in patients with chronic lymphocytic leukemia
Time frame: Up to 1 year
Population: Data was not collected due to low accrual
Secondary
Incidence of Infections
To study the incidence of infections for up to 1 year following activated T cell infusion
Time frame: Up to 1 year
Population: Data was not collected due to low accrual
Secondary
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.
Time frame: Up to 1 year
Population: Data was not collected due to low accrual