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

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02530515
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 8
• Location: 1
• Arm: 1
• Actual Duration (Months): 28.4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Biological: Ex Vivo-activated Autologous Lymph Node Lymphocytes; Other: Laboratory Biomarker Analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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:

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

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

3. 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 Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Trial of Immune Reconstitution With Activated T-Cells in Patients With Chronic Lymphocytic Leukemia (CLL)
• Actual Study Start Date: Dec 18, 2015
• Actual Primary Completion Date: Apr 30, 2018
• Actual Study Completion Date: Apr 30, 2018

Arms and Interventions

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.	Biological: Ex Vivo-activated Autologous Lymph Node Lymphocytes; Given IV; Other Names: X-ACT X-ACT Autologous Lymph Node Lymphocytes ; Other: Laboratory Biomarker Analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. 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

1. Immune Reconstitution [Up to 1 year]

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

2. 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.

3. Incidence of Infections [Up to 1 year]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	M D Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Chitra Hosing, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 17, 2017

More Information

Additional Information:

• MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT02530515
• Other Study ID Numbers: 2014-0830; NCI-2015-01546; 2014-0830; P30CA016672
• First Posted: Aug 21, 2015
• Last Update Posted: Oct 29, 2019
• Last Verified: Oct 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Communicable Diseases; Infections; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic; Thrombocytopenia; Lymphadenopathy; Lymphocytosis; Weight Loss

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Arm A	Arm B	Arm C
Arm/Group Description	Receive lymphodepletion chemotherapy followed by activated T-cell infusion	Receive lymphodepletion chemotherapy followed by activated T-cell infusion followed by low dose lenalidomide PO once ANC is>1.5x109/L	Patients who cannot receive lymphodepleting chemotherapy (as determined by the treating physician) or those with 17p deletion
Period Title: Overall Study
STARTED	0	0	8
COMPLETED	0	0	8
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Arm A	Arm B	Arm C	Total
Arm/Group Description	Receive lymphodepletion chemotherapy followed by activated T-cell infusion	Receive lymphodepletion chemotherapy followed by activated T-cell infusion followed by low dose lenalidomide PO once ANC is>1.5x109/L	Patients who cannot receive lymphodepleting chemotherapy (as determined by the treating physician) or those with 17p deletion	Total of all reporting groups
Overall Participants	0	0	8	8
Age (Count of Participants)
<=18 years	0 NaN	0 NaN	0 0%	0 0%
Between 18 and 65 years	0 NaN	0 NaN	1 12.5%	1 12.5%
>=65 years	0 NaN	0 NaN	7 87.5%	7 87.5%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	74.5	74.5
Sex: Female, Male (Count of Participants)
Female	0 NaN	0 NaN	4 50%	4 50%
Male	0 NaN	0 NaN	4 50%	4 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 NaN	0 NaN	0 0%	0 0%
Not Hispanic or Latino	0 NaN	0 NaN	7 87.5%	7 87.5%
Unknown or Not Reported	0 NaN	0 NaN	1 12.5%	1 12.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 NaN	0 NaN	0 0%	0 0%
Asian	0 NaN	0 NaN	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 NaN	0 NaN	0 0%	0 0%
Black or African American	0 NaN	0 NaN	0 0%	0 0%
White	0 NaN	0 NaN	7 87.5%	7 87.5%
More than one race	0 NaN	0 NaN	0 0%	0 0%
Unknown or Not Reported	0 NaN	0 NaN	1 12.5%	1 12.5%

Outcome Measures

1. Primary Outcome

Title	Treatment Success and Feasibility of Autologous Activated T-cells Infusion, Determined by Number of Participants That Achieved Target-Activated T-cell Dose Without DLT.
Description	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.

Outcome Measure Data

Analysis Population Description

Patients with CLL.

Arm/Group Title	Arm A	Arm B	Arm C
Arm/Group Description	Receive lymphodepletion chemotherapy followed by activated T-cell infusion	Receive lymphodepletion chemotherapy followed by activated T-cell infusion followed by low dose lenalidomide PO once ANC is>1.5x109/L	Patients who cannot receive lymphodepleting chemotherapy (as determined by the treating physician) or those with 17p deletion
Measure Participants	0	0	8
Sucessful Target T-cell Dose	7 Infinity
Feasibility	7 Infinity

2. Secondary Outcome

Title	Immune Reconstitution
Description	To study immune reconstitution following infusion of activated T-cells in patients with chronic lymphocytic leukemia
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

Data was not collected due to low accrual

Arm/Group Title	Arm A	Arm B	Arm C
Arm/Group Description	Receive lymphodepletion chemotherapy followed by activated T-cell infusion	Receive lymphodepletion chemotherapy followed by activated T-cell infusion followed by low dose lenalidomide PO once ANC is>1.5x109/L	Patients who cannot receive lymphodepleting chemotherapy (as determined by the treating physician) or those with 17p deletion
Measure Participants	0	0	0

3. Secondary Outcome

Title	Overall Response Rates
Description	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

Outcome Measure Data

Analysis Population Description

Data was not collected due to low accrual

Arm/Group Title	Arm A	Arm B	Arm C
Arm/Group Description	Receive lymphodepletion chemotherapy followed by activated T-cell infusion	Receive lymphodepletion chemotherapy followed by activated T-cell infusion followed by low dose lenalidomide PO once ANC is>1.5x109/L	Patients who cannot receive lymphodepleting chemotherapy (as determined by the treating physician) or those with 17p deletion
Measure Participants	0	0	0

4. Secondary Outcome

Title	Incidence of Infections
Description	To study the incidence of infections for up to 1 year following activated T cell infusion
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

Data was not collected due to low accrual

Arm/Group Title	Arm A	Arm B	Arm C
Arm/Group Description	Receive lymphodepletion chemotherapy followed by activated T-cell infusion	Receive lymphodepletion chemotherapy followed by activated T-cell infusion followed by low dose lenalidomide PO once ANC is>1.5x109/L	Patients who cannot receive lymphodepleting chemotherapy (as determined by the treating physician) or those with 17p deletion
Measure Participants	0	0	0

Adverse Events

Time Frame	Up to 100 Days post T cell infusion.
Adverse Event Reporting Description	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.
Arm/Group Title	Arm A		Arm B		Arm C
Arm/Group Description	Receive lymphodepletion chemotherapy followed by activated T-cell infusion		Receive lymphodepletion chemotherapy followed by activated T-cell infusion followed by low dose lenalidomide PO once ANC is>1.5x109/L		Patients who cannot receive lymphodepleting chemotherapy (as determined by the treating physician) or those with 17p deletion
All Cause Mortality
	Arm A		Arm B		Arm C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/8 (0%)
Serious Adverse Events
	Arm A		Arm B		Arm C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Arm A		Arm B		Arm C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		8/8 (100%)
Blood and lymphatic system disorders
Anemia	0/0 (NaN)		0/0 (NaN)		3/8 (37.5%)	3
Cardiac disorders
Hypertension	0/0 (NaN)		0/0 (NaN)		1/8 (12.5%)	1
Ear and labyrinth disorders
Hearing impaired	0/0 (NaN)		0/0 (NaN)		1/8 (12.5%)	1
Gastrointestinal disorders
Mucositis	0/0 (NaN)		0/0 (NaN)		1/8 (12.5%)	1
Constipation	0/0 (NaN)		0/0 (NaN)		1/8 (12.5%)	1
General disorders
Edema limbs	0/0 (NaN)		0/0 (NaN)		1/8 (12.5%)	1
Fatigue	0/0 (NaN)		0/0 (NaN)		1/8 (12.5%)	1
Infections and infestations
Eye Infection	0/0 (NaN)		0/0 (NaN)		1/8 (12.5%)	1
Nail Infection	0/0 (NaN)		0/0 (NaN)		1/8 (12.5%)	1
Sinusitis	0/0 (NaN)		0/0 (NaN)		1/8 (12.5%)	1
Investigations
Platelet Count Decreased	0/0 (NaN)		0/0 (NaN)		2/8 (25%)	2
Metabolism and nutrition disorders
Anorexia	0/0 (NaN)		0/0 (NaN)		1/8 (12.5%)	1
Hypercalcemia	0/0 (NaN)		0/0 (NaN)		1/8 (12.5%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonitis	0/0 (NaN)		0/0 (NaN)		4/8 (50%)	4
Upper Respiratory Infection	0/0 (NaN)		0/0 (NaN)		2/8 (25%)	2
Allergic rhinitis	0/0 (NaN)		0/0 (NaN)		1/8 (12.5%)	1
Cough	0/0 (NaN)		0/0 (NaN)		1/8 (12.5%)	1
Skin and subcutaneous tissue disorders
Skin Other	0/0 (NaN)		0/0 (NaN)		1/8 (12.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.