NCT02274506

Brief Summary

The goal of this clinical research study is to learn if researchers can successfully and safely give patients who have had a stem cell transplant an infusion of white blood cells (called T-cells) that have been collected from an unrelated person, and that have been genetically changed. The process of changing the DNA (genetic material) of these T-cells is called "gene transfer." The gene transfer involves drawing blood from an unrelated donor, separating out T cells using a machine, changing the cells' DNA in the laboratory, and returning the genetically changed cells back to the body. T-cells are a type of white blood cell that fight infection. The type of gene transfer being used in this study is designed to help your T-cells to better fight cancer by targeting a chemical marker that is found on certain cancer cells. Researchers want to learn if these genetically-changed T-cells can help to control B-cell leukemia or lymphoma after a stem cell transplant. Researchers want to find out the highest tolerable dose of these T-cells that can be given to patients with relapsed leukemia or lymphoma.

Trial Health

15
At Risk

Trial Health Score

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

Trial has exceeded expected completion date
Timeline
Completed

Started Oct 2014

Status
withdrawn

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

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 20, 2014

Completed
Same day until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 20, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 20, 2014

Completed
2 days until next milestone

First Submitted

Initial submission to the registry

October 22, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

October 24, 2014

Completed
Last Updated

January 22, 2020

Status Verified

January 1, 2020

Enrollment Period

Same day

First QC Date

October 22, 2014

Last Update Submit

January 17, 2020

Conditions

Blood And Marrow TransplantationLeukemiaLymphoma

Keywords

Blood And Marrow TransplantationLeukemiaLymphomaCD19-specific T cellsAcute lymphoblastic leukemiaALLBiphenotypic leukemiaNon-Hodgkin's LymphomaNHLDiffuse large B-cell lymphomaSmall lymphocytic lymphomaFollicular lymphomaMantle cell lymphomaChronic lymphocytic leukemiaCLL

Outcome Measures

Primary Outcomes (1)

  • Maximum Tolerated Dose (MTD) of CD19-Specific T Cells

    Maximum tolerated dose (MTD) is highest dose level 6 patients treated, with at most 2 experiencing dose limiting toxicity (DLT). DLT defined as new adverse event attributable to CD19-specific T cells of grade \>3 that lasts for more than 3 days, and related to CD19-specific T cells within 30 days of an infusion. Grade 3/4 graft versus host disease (GVHD) occurring within 6 weeks of CD19-specific T cells administration, also a DLT. Graft failure following CD19-specific T cells administration considered DLT.

    12 hours

Study Arms (1)

T-Cell Administration

EXPERIMENTAL

Cyclophosphamide 60 mg/kg by vein for 2 consecutive days, followed by Fludarabine at 25 mg/m2/day by vein for 5 consecutive days. Fludarabine dose calculated per adjusted ideal body weight. T-cell product divided into 2 portions. Up to 25% of the genetically modified cells given on first day, with plan to infuse up to 75% of the remaining T-cell dose no sooner than 24 hours after completion of first portion. Second portion should not be given later than 72 hours after first portion. First group of 3 participants receive lowest dose of T-cells. Each new group receive a higher dose of T-cells than the group before it, if no intolerable side effects were seen. Up to 6 dose levels of T-cells will be tested.

Drug: CyclophosphamideDrug: FludarabineProcedure: T-Cell Infusion

Interventions

CyclophosphamideDRUG

60 mg/kg by vein on Days -8 and -7.

Also known as: Cytoxan, Neosar
T-Cell Administration
FludarabineDRUG

25 mg/m2 by vein on Days -6 to -2.

Also known as: Fludarabine Phosphate, Fludara
T-Cell Administration
T-Cell InfusionPROCEDURE

T-cells infused no sooner than 48 hours and no later than 1 week post completion of chemotherapy on Day 0.

T-Cell Administration

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with a history of refractory B-cell lymphoid malignancies: 1) acute lymphoblastic leukemia (ALL), CD19+, 2) biphenotypic leukemia CD19+, 3) non-Hodgkin's Lymphoma (NHL), which includes diffuse large B-cell lymphoma, small lymphocytic lymphoma, follicular lymphoma, mantle cell lymphoma, or chronic lymphocytic leukemia (CLL).
  • Age 18 to 70 years.
  • Zubrod performance 0-2 or Karnofsky greater than or equal to 60%.
  • Patient or patient's legal representative able to provide written informed consent.
  • Patient or patient's legal representative able to provide written informed consent for the long-term follow-up gene therapy study.
  • Patients must be a minimum of 3 months from last hematopoietic stem cell transplant (HSCT) and 3 weeks from last systemic chemotherapy.

You may not qualify if:

  • Patients with known allergy to bovine or murine products.
  • Clinically significant acute or chronic GVHD requiring systemic immunosuppression, including methylprednisolone \>/= 1 mg/kg/day.
  • Systemic corticosteroid use within 72 hours of treatment initiation.
  • Antibody to HLA expressed on 3rd party T cells.
  • Experiencing any new Grade \>2 (CTC version 4) adverse neurologic, pulmonary, cardiac, gastrointestinal, renal or hepatic (excluding albumin) event within 24 hours prior to treatment initiation.
  • Active infection defined as positive culture, if available, for bacteria, fungus, or virus within a 3-day period prior to treatment initiation and/or fever greater than 38°C within 24 hours prior to treatment initiation.
  • Positive beta HCG by qualitative pregnancy test in female of child-bearing potential defined as not post menopausal for 12 months or absence of previous surgical sterilization.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Links

MeSH Terms

Conditions

LeukemiaLymphomaPrecursor Cell Lymphoblastic Leukemia-LymphomaLymphoma, Non-HodgkinLymphoma, Large B-Cell, DiffuseLeukemia, Lymphocytic, Chronic, B-CellLymphoma, FollicularLymphoma, Mantle-Cell

Interventions

Cyclophosphamidefludarabinefludarabine phosphate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Study Officials

  • Partow Kebriaei, MD

    M.D. Anderson Cancer Center

    PRINCIPAL INVESTIGATOR
0

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

October 22, 2014

First Posted

October 24, 2014

Study Start

October 20, 2014

Primary Completion

October 20, 2014

Study Completion

October 20, 2014

Last Updated

January 22, 2020

Record last verified: 2020-01