NCT01362452

Brief Summary

The goal of this clinical research study is to learn if an infusion of white blood cells (called T cells) that have been genetically changed is safe to give patients who have received an umbilical cord blood transplant (UCBT). Researchers want to learn if these genetically changed T-cells are effective in attacking cancer cells in patients with advanced B-cell lymphoma or leukemia after they have received an UCBT, how long the changed T-cells stay in the body, and if adding them to standard transplant could improve how patients respond to treatment. Funding Source - FDA OOPD

Trial Health

87
On Track

Trial Health Score

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

Enrollment
5

participants targeted

Target at below P25 for phase_1 leukemia

Timeline
Completed

Started Dec 2012

Typical duration for phase_1 leukemia

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

May 26, 2011

Completed
4 days until next milestone

First Posted

Study publicly available on registry

May 30, 2011

Completed
1.5 years until next milestone

Study Start

First participant enrolled

December 7, 2012

Completed
4.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 25, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 25, 2017

Completed
Last Updated

August 3, 2017

Status Verified

August 1, 2017

Enrollment Period

4.6 years

First QC Date

May 26, 2011

Last Update Submit

August 2, 2017

Conditions

LeukemiaLymphoma

Keywords

LeukemiaLymphomaCD19-specific T cellsUmbilical cord blood transplantationB-Lineage Lymphoid MalignanciesB-cell leukemiaAcute Lymphoblastic LeukemiaALLBiphenotypic LeukemiaNon-Hodgkin's LymphomaNHLSmall Lymphocytic LymphomaSLLChronic Lymphocytic LeukemiaCLLWhite blood cellsT cellsMelphalanAlkeranThiotepaFludarabineFludarabine PhosphateFludaraATGAntithymocyte GlobulinThymoglobulinRituxanRituximabCyclophosphamideCytoxanNeosar

Outcome Measures

Primary Outcomes (1)

  • Maximum Tolerated Dose (MTD) of T-Cell Infusions

    MTD is highest dose level in which 6 participants treated with at most 2 experiencing dose-limiting toxicity (DLT) using Common Toxicity Criteria (CTC) following the t-cell infusion Day 42 to Day 100.

    30 days following T-Cell infusion (up to 130 days)

Secondary Outcomes (1)

  • Secondary Graft Failure of T-Cell Infusions

    30 days after t-cell infusion

Study Arms (2)

Double Umbilical Cord Blood (UCB)

EXPERIMENTAL

Infusion of CD19-specific T cells derived from cord blood (CB) 42 days following stem cell transplantation. Starting dose level of T-cells not to exceed 106/m2. The investigational component of the treatment plan of this study is the infusion of CD19-specific T cells derived from cord blood (CB) to be infused Day +42 to Day +100 following stem cell transplantation. The transplant component of the treatment plan will include CB transplant regimens that are commonly use for CB transplantation.

Genetic: T-Cell InfusionProcedure: Cord Blood Infusion

Single Umbilical Cord Blood (UCB)

EXPERIMENTAL

Single UCB unit arm does not start enrollment until Dose Level A2 in the double UCB unit arm has been deemed safe. Infusion of CD19-specific T cells derived from cord blood (CB) 42 days following stem cell transplantation. Starting dose level of T-cells not to exceed 106/m2. The investigational component of the treatment plan of this study is the infusion of CD19-specific T cells derived from cord blood (CB) to be infused Day +42 to Day +100 following stem cell transplantation. The transplant component of the treatment plan will include CB transplant regimens that are commonly use for CB transplantation

Genetic: T-Cell InfusionProcedure: Cord Blood Infusion

Interventions

T-Cell InfusionGENETIC

Infusion of CD19-specific T cells derived from cord blood (CB) 42 days following stem cell transplantation.

Double Umbilical Cord Blood (UCB)Single Umbilical Cord Blood (UCB)
Cord Blood InfusionPROCEDURE

Cord blood infusion on Day 0.

Double Umbilical Cord Blood (UCB)Single Umbilical Cord Blood (UCB)

Eligibility Criteria

Age1 Year - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with a history of CD19+ lymphoid malignancies that are primary refractory to treatment (do not achieve complete remission after first course of therapy) or are beyond first remission including second or greater remission or active disease.
  • Patients in first remission are eligible if they are considered high risk, defined as any of the following detected at any time: 1) Acute Lymphoblastic Leukemia (ALL) with translocations 9;22 or 4;11, hypodiploidy, complex karyotype, secondary leukemia developing after cytotoxic drug exposure,and/or evidence of minimal residual disease; or, 2) Acute biphenotypic leukemia; or, 3) Double hit nonHodgkin's lymphoma; or, 4) Non-Hodgkin's Lymphoma (NHL) in second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant). Double hit lymphomas in first remission or more advanced disease; or, 5) Small Lymphocytic Lymphoma (SLL), or Chronic Lymphocytic Leukemia (CLL) with progressive disease following standard therapy.
  • Age 1 to 75 years old.
  • Performance score of at least 80% by Karnofsky or PS \< 3 (ECOG) (age \>/= 12 years), or Lansky Play-Performance Scale of at least 60% or greater (age \<12 years).
  • Two Cord Blood units identified that are matched with the patient at 4/6, 5/6, or 6/6 HLA class I (serological) and II (molecular) antigens. Each cord must contain at least 1.5 x 10\^7 total nucleated cells/Kg recipient body weight (pre-thaw). One Cord Blood unit may be used (in lieu of two) if it contains at least 2.5 x 10\^7 total nucleated cells/Kg recipient body weight (pre-thaw).
  • Have identified a back up cells source in case of engraftment failure. The source can be autologous, related or unrelated.
  • Cardiac Function: left ventricular ejection fraction \>/= 40%.
  • Pulmonary function: forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and diffusing capacity of lung for carbon monoxide (DLCO) \>/= 50% of expected, corrected for hemoglobin. For children \</= 7 years of age who are unable to perform pulmonary function testing (PFT), oxygen saturation \>/= 92% on room air by pulse oximetry.
  • Renal function: Serum creatinine \</= 1.8mg/dl or \</= 2 x upper limit of normal or creatinine clearance greater or equal than 40 cc/min. Creatinine for pediatric patients \</=1.5 mg/dl or \</=2 times upper limit of normal for age (whichever is less).
  • Liver function: Bilirubin \</= 1.5 mg/dl or \</= 4 x upper limit of normal (unless Gilbert's syndrome), ALT or AST \</= 200 IU/ml or \</= 5 x upper limit of normal for adults unless related to underline disease. For pediatric patients conjugated (direct) bilirubin \< 2x upper limit of normal, ALT or AST \< 5 times upper limit of normal.
  • Negative Beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization and willing to use an effective contraceptive measure while on study.
  • Patient or patient's legal representative, parent(s) or guardian able to provide written informed consent. Assent of a minor if participant's age is at least seven and less than eighteen years.
  • 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 HCG in female of child-bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization or breast-feeding.
  • Patients with known allergy to bovine or murine products.
  • Patients with known history of HIV/AIDS.
  • Patients with chronic active hepatitis or cirrhosis. If positive hepatitis serology, the Study Chair may deem the patient eligible based on the results of liver biopsy.
  • Patients positive for West Nile Virus or RPR.
  • If in the opinion of PI or designee, the research participant has a significant active medical illness or condition deemed to potentially impact negatively on trial participation.

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

LeukemiaLymphomaLeukemia, B-CellPrecursor Cell Lymphoblastic Leukemia-LymphomaLymphoma, Non-HodgkinLeukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLeukemia, LymphoidChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Elizabeth Shpall, MD

    M.D. Anderson Cancer Center

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 26, 2011

First Posted

May 30, 2011

Study Start

December 7, 2012

Primary Completion

July 25, 2017

Study Completion

July 25, 2017

Last Updated

August 3, 2017

Record last verified: 2017-08

Locations

US(1)