NCT01653717

Brief Summary

The goal of this clinical research study is to find the highest tolerable dose of T cells that can be given in combination with standard chemotherapy to patients with CLL. The safety of this combination will also be studied. The T cells being used in this study are a type of white blood cell that will be taken from your blood and then genetically changed in a laboratory. The process of changing the DNA (the genetic material of cells) of the T cells is called a gene transfer. After the gene transfer is complete, the genetically changed T-cells will be put back into your body. These T cells may help prevent cancer cells from coming back.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Jun 2013

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 27, 2012

Completed
4 days until next milestone

First Posted

Study publicly available on registry

July 31, 2012

Completed
11 months until next milestone

Study Start

First participant enrolled

June 11, 2013

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 7, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 7, 2017

Completed
Last Updated

August 17, 2017

Status Verified

August 1, 2017

Enrollment Period

4.2 years

First QC Date

July 27, 2012

Last Update Submit

August 14, 2017

Conditions

Keywords

Advanced CancersLeukemiaB-cell Chronic Lymphocytic LeukemiaB-CLLCD19 positivityCD19-specific T cellsT-Cell InfusionGene TransferLeukapheresisFludarabineFludarabine PhosphateFludaraCyclophosphamideCytoxanNeosar

Outcome Measures

Primary Outcomes (1)

  • Maximum Tolerated Dose (MTD) of CD19-specific T-cells

    Maximum tolerated dose (MTD) defined as the highest dose for which the posterior probability of toxicity is closest to 25%. Dose limiting toxicity (DLT) defined as new adverse events of grade 3+ (CTCAE version 4) involving cardiopulmonary, gastrointestinal, hepatic (excluding albumin), neurological, or renal parameters occurring with 6 weeks of infusion that are probably or definitely related to T-cell product. The maximum acceptable toxicity rate is 25%.

    12 months

Secondary Outcomes (1)

  • Clinically Successful T-Cell Production

    7 weeks

Study Arms (1)

T-Cell Infusion + Chemotherapy

EXPERIMENTAL

Peripheral blood mononuclear cells (PBMC) collected via venipuncture or steady state leukapheresis after enrollment. Clinically successful T-cell production defined as amount of T-cells required for dose level for which the patient is enrolled. Fludarabine 25 mg/m2 by vein on Days -5 to Day -3. Cyclophosphamide 250 mg/kg by vein on Days -5 to -3. Beginning dose of genetically modified cells is \> 5x10\^7/m2 but less than or equal to 5 x10\^8/m2 infused on Day 0.

Procedure: LeukapheresisDrug: FludarabineDrug: CyclophosphamideProcedure: T-cell Infusion

Interventions

LeukapheresisPROCEDURE

Blood drawn through a needle in a vein in one arm, then passed though a machine to collect white blood cells, and then remaining blood returned back to patient through a needle in a vein in other arm. Procedure will take about 3 hours to complete.

T-Cell Infusion + Chemotherapy

25 mg/m2 by vein on Days -5 to Day -3.

Also known as: Fludarabine Phosphate, Fludara
T-Cell Infusion + Chemotherapy

250 mg/kg by vein on Days -5 to -3.

Also known as: Cytoxan, Neosar
T-Cell Infusion + Chemotherapy

Beginning dose of genetically modified cells is \> 5x10\^7/m2 but less than or equal to 5 x10\^8/m2 infused on Day 0.

T-Cell Infusion + Chemotherapy

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with a history of B-CLL, who have received at least 2 lines of standard chemoimmunotherapy and have persistent disease.
  • Confirmed history of CD19 positivity by flow cytometry.
  • At least 8 weeks from last cytotoxic chemotherapy. Patients may continue ibrutinib or lenalidomide. These drugs will be discontinued 1 week prior to start of lymphodepleting chemotherapy.
  • Karnofsky Performance Scale \> 60%.
  • Absolute lymphocyte count \>100/uL.
  • Adequate hepatic function, as defined by serum glutamate pyruvate (SGPT) \<3 x upper limit of normal; serum bilirubin and alkaline phosphatase \<2 x upper limit of normal, or considered not clinically significant by the study doctor or designee.
  • Able to provide written informed consent.
  • years of age.
  • Patient or patient's legal representative, parent(s) or guardian able to provide written informed consent for the long-term follow-up gene therapy study.

You may not qualify if:

  • Positive beta human chorionic gonadotropin (HCG) in female of child-bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization or lactating females.
  • Patients with known allergy to bovine or murine products.
  • Positive serology for HIV.
  • Presence of autoimmune phenomenon (AIHA, ITP) requiring steroid therapy.
  • Presence of Grade 3 or greater toxicity from the previous treatment.
  • Concomitant use of other investigational agents (ibrutinib or lenalidomide are allowed).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

MeSH Terms

Conditions

LeukemiaLeukemia, Lymphocytic, Chronic, B-Cell

Interventions

Leukapheresisfludarabinefludarabine phosphateCyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLeukemia, B-CellLeukemia, LymphoidLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

CytapheresisBiological TherapyTherapeuticsBlood Component RemovalLeukocyte Reduction ProceduresCell SeparationCytological TechniquesClinical Laboratory TechniquesInvestigative TechniquesPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Study Officials

  • Chitra M. Hosing, MD

    M.D. Anderson Cancer Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 27, 2012

First Posted

July 31, 2012

Study Start

June 11, 2013

Primary Completion

August 7, 2017

Study Completion

August 7, 2017

Last Updated

August 17, 2017

Record last verified: 2017-08

Locations