We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02530515
Recruitment Status : Active, not recruiting
First Posted : August 21, 2015
Last Update Posted : July 14, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:

Patient's immune systems are often damaged by chemotherapy or by CLL. Researchers want to learn if giving T-cells (immune cells) that have been expanded and specially processed in the laboratory (activated) will help CLL patients' immune systems recover after chemotherapy. This may help lower the chance of infections.

The goal of this clinical research study is to learn if an activated T-cell infusion, when given with or without lenalidomide, can help to restore patients' immune systems when given after chemotherapy (rituximab and fludarabine with cyclophosphamide or bendamustine). The safety of this treatment combination will also be studied.

Researchers also want to learn if the activated T-cells may also be able to kill cancer cells.


Condition or disease Intervention/treatment Phase
Leukemia Chronic Lymphocytic Leukemia Drug: Rituximab Drug: Cyclophosphamide Drug: Fludarabine monophosphate Drug: Bendamustine Biological: Activated T-Cell Infusion Drug: Lenalidomide Behavioral: Phone Calls Phase 2

  Show Detailed Description

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Trial of Immune Reconstitution With Activated T-Cells Following Lymphodepleting Chemotherapy in Patients With Chronic Lymphocytic Leukemia (CLL)
Actual Study Start Date : December 18, 2015
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020


Arms and Interventions

Arm Intervention/treatment
Experimental: Chemotherapy + Activated T-Cell Infusion

Participants receive Rituximab by vein on Day -5.

Participants receive Fludarabine and Cyclophosphamide by vein on Day -5, -4 and -3.

Participant receives activated T-cells by vein on Day 0.

Study staff calls participant starting about a year and a half after the activated T-cell infusion every 6 months for up to 5 years.

Drug: Rituximab
375 mg/m2 by vein on Day -5.
Other Name: Rituxan
Drug: Cyclophosphamide
250 mg/m2 by vein on Days -5, -4, and -3 per treating physician decision.
Other Names:
  • Cytoxan
  • Neosar
Drug: Fludarabine monophosphate

Chemotherapy + Activated T-Cell Infusion Group: 25 mg/m2 by vein on Day -5, -4, and -3.

Chemotherapy + Activated T-Cell Infusion + Lenalidomide Group: 20 mg/m2 by vein on Day -5, -4, and -3.

Other Names:
  • Fludarabine Phosphate
  • Fludara
Biological: Activated T-Cell Infusion
Activated T-cell infusion, approximately 1 x 10^10, by vein on Day 0.
Behavioral: Phone Calls
Study staff calls participant starting about a year and a half after the activated T-cell infusion every 6 months for up to 5 years.
Experimental: Chemotherapy + Activated T-Cell Infusion + Lenalidomide

Participants receive Rituximab by vein on Day -5.

Participants receive Fludarabine and Bendamustine by vein on Day -5, -4 and -3,

Participant receives activated T-cells by vein on Day 0.

Participants receive Lenalidomide by mouth 1 time each day for about 6 months after blood counts are high enough after activated T-cell infusion.

Study staff calls participant starting about a year and a half after the activated T-cell infusion every 6 months for up to 5 years.

Drug: Rituximab
375 mg/m2 by vein on Day -5.
Other Name: Rituxan
Drug: Cyclophosphamide
250 mg/m2 by vein on Days -5, -4, and -3 per treating physician decision.
Other Names:
  • Cytoxan
  • Neosar
Drug: Fludarabine monophosphate

Chemotherapy + Activated T-Cell Infusion Group: 25 mg/m2 by vein on Day -5, -4, and -3.

Chemotherapy + Activated T-Cell Infusion + Lenalidomide Group: 20 mg/m2 by vein on Day -5, -4, and -3.

Other Names:
  • Fludarabine Phosphate
  • Fludara
Drug: Bendamustine
30 mg/m2 by vein on Days -5, -4, and -3 per treating physician decision.
Other Names:
  • Bendamustine Hydrochloride
  • Bendamustine HCL
  • CEP-18083
  • SDX-105
  • Treanda
Biological: Activated T-Cell Infusion
Activated T-cell infusion, approximately 1 x 10^10, by vein on Day 0.
Drug: Lenalidomide
5 mg by mouth 1 time each day for about 6 months after blood counts are high enough after activated T-cell infusion.
Other Names:
  • CC-5013
  • Revlimid
Behavioral: Phone Calls
Study staff calls participant starting about a year and a half after the activated T-cell infusion every 6 months for up to 5 years.
Experimental: Activated T-Cell Infusion 17p Deletion Group

Participants receive expanded T cells without lymphodepleting chemotherapy.

Study staff calls participant starting about a year and a half after the activated T-cell infusion every 6 months for up to 5 years.

Biological: Activated T-Cell Infusion
Activated T-cell infusion, approximately 1 x 10^10, by vein on Day 0.
Behavioral: Phone Calls
Study staff calls participant starting about a year and a half after the activated T-cell infusion every 6 months for up to 5 years.


Outcome Measures

Primary Outcome Measures :
  1. Success of Autologous T Cells for Immune Restoration in Participants with Chronic Lymphocytic Leukemia (CLL) [ Time Frame: 90 days ]
    Success defined as achievement of a target activated T-cell dose of 1 x 108 +/- 20% and lack of dose limiting toxicity (DLT). DLT 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 (CTC v4.03 CTCAE) 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.

  2. Feasibility of Autologous T Cells for Immune Restoration in Participants with Chronic Lymphocytic Leukemia (CLL) [ Time Frame: 90 days after T-cell infusion ]
    Feasibility defined as achievement of the target T cell dose (1 x 108 +/- 20%) in > 50% of patients enrolled.


Secondary Outcome Measures :
  1. Immune Reconstitution Following Infusion of Activated T-cells in Participants with Chronic Lymphocytic Leukemia in the Lenalidomide and Non-Lenalidomide Arms [ Time Frame: 28 days, 90 days, and 1 year after T-cell infusion ]
    Percentages and absolute values of CD3+, CD4+, CD8+ and CD4/CD8 ratio assessed and reported at each time point along with 95% confidence intervals. Immune reconstitution compared at each time point between the treatment arms.


Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. All patients must have a diagnosis of CLL by immunophenotyping and flow cytometry analysis of blood or bone marrow. 1) Patients must meet criteria for treatment based on the criteria proposed by NCI-sponsored CLL Working Group to include at least one of the following: a) weight loss of more than 10% over the preceding 6 months; or, b) extreme fatigue attributable to progressive disease; or, c) fever or night sweats without evidence of infection; or, d) worsening anemia (Rai stage Ill) or thrombocytopenia (Rai stage IV); or, e) massive lymphadenopathy (>10 cm) or rapidly progressive lymphocytosis (lymphocyte doubling time <6 months); or, f) prolymphocytic or Richter's transformation; or, 2) Patients with CLL who have received at least one prior line of therapy; or, 3) Patients with CLL who have frequent infections and/or recurrent secondary cancers.
  2. No active CNS disease.
  3. All patients must have a Karnofsky Performance Score > 60%.
  4. Calculated creatinine clearance (by Cockcroft-Gault) of > 50 ml/min.
  5. Patients must not have untreated or uncontrolled life-threatening infection.
  6. Patients must sign informed consent.
  7. Females of childbearing potential must have a negative serum pregnancy test with a minimum sensitivity of 50 mIU/mL and agree to use two medically accepted forms of contraception from the time of initial screening through completion of the study or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting lenalidomide; 2) throughout the entire duration of lenalidomide treatment; 3) during dose interruptions; and 4) for at least 28 days after lenalidomide discontinuation.
  8. Females of reproductive potential who will receive lenalidomide must adhere to the scheduled pregnancy testing as required in the Revlimid REMS(TM) program.
  9. Men must agree to use a latex condom during sexual contact with females of child bearing potential even if they have had a successful vasectomy.
  10. All study participants who will receive lenalidomide must be registered into the mandatory Revlimid REMS(TM) program, and be willing and able to comply with the requirements of the REMS(TM) program.
  11. Patients who meet eligibility for the protocol but are not candidates to receive further chemotherapy may be treated on Arm C.
  12. Patients with 17p deletion can only be enrolled on Arm C. These patients will receive the expanded T cells without lymphodepleting chemotherapy.

Exclusion Criteria:

  1. Receipt of glucocorticoids (with the exception of inhaled glucocorticoid steroids for the use of allergic rhinitis or pulmonary disease) within 2 weeks of registration.
  2. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02530515


Locations
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Chitra M. Hosing, MD M.D. Anderson Cancer Center
More Information

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02530515     History of Changes
Other Study ID Numbers: 2014-0830
NCI-2015-01546 ( Registry Identifier: NCI CTRP )
First Posted: August 21, 2015    Key Record Dates
Last Update Posted: July 14, 2017
Last Verified: July 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Leukemia
Chronic Lymphocytic Leukemia
CLL
T-cells
Immune cells
Rituximab
Rituxan
Cyclophosphamide
Cytoxan
Neosar
Fludarabine Phosphate
Fludarabine
Fludara
Bendamustine
Bendamustine Hydrochloride
Bendamustine HCL
CEP-18083
SDX-105
Treanda
Lenalidomide
CC-5013
Revlimid

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Cyclophosphamide
Thalidomide
Fludarabine phosphate
Rituximab
Bendamustine Hydrochloride
Lenalidomide
Fludarabine
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances