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Donor-Derived, CD19-Specific T Cell Infusion in Patients With B-Lineage Lymphoid Malignancies After Umbilical Cord Blood Transplantation


Phase 1
1 Year
75 Years
Open (Enrolling)
Both
Leukemia, Lymphoma

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Trial Information

Donor-Derived, CD19-Specific T Cell Infusion in Patients With B-Lineage Lymphoid Malignancies After Umbilical Cord Blood Transplantation


T-cell infusion:

The gene transfer used in this study involves umbilical cord blood cells taken either from
your UCB unit(s) or from cells left over after your UCB unit has been processed. Researchers
perform a gene transfer to change the T-cells' DNA (the genetic material of cells), and then
inject the changed T-cells into the body of the patient receiving the transplant. This
process is called a modified donor lymphocyte infusion (DLI) or T-cell infusion.

Chemotherapy and UCBT:

After the umbilical cord blood unit has been identified for your transplant and after it has
arrived at the hospital, you will be admitted to the hospital to receive chemotherapy and
the UCBT. These procedures are not considered part of this research study. You will
discuss these procedures with a study doctor and sign an informed consent document with
specific details of the UCBT procedure and possible risks, at another time.

You will be given standard drugs to help decrease the risk of side effects. You may ask the
study staff for information about how the drugs are given and their risks.

The T-cell Infusions:

After the UCBT, the study doctor will decide when you will be eligible for the T-cell
infusions. You must be at least 42 days past your UCBT without any serious evidence of
active graft versus host disease (GVHD). GVHD occurs when the donor cells attack the cells
of the person receiving the transplant.

The T-cell infusion is given by vein, usually over 15-30 minutes over 2 days. A smaller
dose of T cells will be infused on the first day and if this is tolerated the remaining dose
of T cells will be infused within 72 hours after the first infusion. During both infusions,
your vital signs will be checked.

Study Tests:

About 30 days and 3, 6, and 12 months after your UCBT:

- You will have a physical exam.

- You will be checked for possible reactions to your treatment, including GVHD and graft
failure. Graft failure occurs when donor cells may not be able to grow and multiply in
your body. If this happens, there will be a high risk of infections and/or bleeding.
If the number of white blood cells does not get back to high enough levels within 30
days after the transplant, stem cells from another cord blood unit or a family member
may need to be given. Your doctor will discuss this with you in more detail.

- Blood (about 4 tablespoons) will be drawn for routine tests and to check for
cytomegalovirus (CMV). CMV is a virus that is common after a cord blood transplant.

- Urine will be collected for routine tests.

Within 7 days before the T-cell infusion:

- You will have a physical exam.

- You will be checked for possible reactions to your UCBT, including GVHD and graft
failure.

- Blood (about 4 tablespoons) will be drawn for routine tests, to check your immune
system, and to check for human anti-mouse antibodies (HAMA). Your body may develop
HAMA as an immune system reaction because mouse protein antibodies are used in the gene
transfer process.

- Blood (about 2 tablespoons) will be drawn for research tests to measure the number of
B-cells and other (non-transplanted) T-cells.

Within 12, 24, and 48 hours, and then about 3 days, 1, 2, and 4 weeks after the T-cell
infusion:

- You will have a physical exam.

- You will be checked for possible reactions to your treatment, including GVHD and graft
failure.

- Blood (about 4 tablespoons) will be drawn for routine tests.

Once during Weeks 2 and 4, and then once a month for 6 months after the T-cell infusion,
blood (about 1 teaspoon) will be drawn to check your immune system. This blood draw may be
done at the same time as the blood draws for routine tests when possible, to avoid extra
"needle sticks".

After the 2nd T-cell infusion:

-Blood (about 2 tablespoons) will be drawn for research tests to check the level of the
infused T-cells and to measure the number of B-cells and other (non-transplanted) T-cells.

About 30 days and 3, 6, and 12 months after the T-cell infusion:

- You will have a physical exam, and you will be checked for possible reactions to your
treatment, including GVHD and graft failure.

- Blood (about 2 tablespoons) will be drawn for research tests to check the level of the
infused T-cells and to measure the number of B-cells and other (non-transplanted)
T-cells. During the Month 3 visit, part of this blood sample will be used to check for
HAMA immune system reactions.

- Urine will be collected for routine tests.

Tests and/or procedures may be repeated more often, if your study doctor thinks it is
needed.

Length of Study:

You may continue taking part in this study for up to 12 months. You will be taken off study
if the disease gets worse, you have any infections, intolerable side effects occur, you are
not able to follow study directions, the T-cells do not engraft (grow in your body), or you
are not able to receive a T-cell infusion.

You should talk to the study doctor if you want to leave the study early. If you are taken
off study early, you still may need to return for routine post-transplant follow-up visits,
or if your transplant doctor decides it is needed.

Your participation on this study will be over once you have completed the planned study
visits at 12 months after the last T-cell infusion.

Long-Term Follow-Up:

For safety reasons, the U.S. Food and Drug Administration (FDA) requires that patients who
receive infusions of stem cells treated with a gene transfer procedure must have long-term
follow-up for at least 15 years after receiving the gene transfer. After you have received
an infusion of the T cells you will be asked to sign a separate consent form for a long-term
follow-up study named Protocol 2006-0676.

This is an investigational study. The gene transfer (or T-cell infusion with genetically
changed T cells) is not commercially available or FDA approved for use in this type of
disease. Gene transfer in this study is considered investigational.

Up to 54 patients will take part in this study. All will be enrolled at MD Anderson.


Inclusion Criteria:



1. Patients with a history of CD19+ lymphoid malignancies that are high risk or
intermediate risk or beyond first relapse or primarily refractory to treatment: Acute
Lymphoblastic Leukemia (ALL) or Biphenotypic Leukemia in first complete remission
with Philadelphia chromosome or translocation 4;11, hypodiploidy, complex karyotype,
and/or evidence of minimal residual disease by flow cytometry; >/= second complete
remission; >/= second relapse; secondary leukemia from prior chemotherapy; active
disease. Non-Hodgkin's Lymphoma (NHL) in second or third complete remission, or
relapse (including relapse post autologous hematopoietic stem cell transplant). Small
Lymphocytic Lymphoma (SLL), or Chronic Lymphocytic Leukemia (CLL) with progressive
disease following standard therapy.

2. Age 1 to 75 years old.

3. Zubrod performance 0-2 (Karnofsky greater than or equal to 50%) or Lansky PS greater
than or equal to 50%.

4. 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).

5. Have identified a back up cells source in case of engraftment failure. The source can
be autologous, related or unrelated.

6. Cardiac Function: left ventricular ejection fraction >/= 40%.

7. Pulmonary function: FEV1, FVC and DLCO >/= 50% of expected, corrected for hemoglobin.
For children /=
92% on room air by pulse oximetry.

8. Renal function: Serum creatinine creatinine clearance greater or equal than 40 cc/min. Creatinine for pediatric
patients less).

9. Liver function: Bilirubin Gilbert's syndrome), ALT or AST 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.

10. 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.

11. 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. Assent of a
minor if participant's age is at least seven and less than eighteen years.

Exclusion Criteria:

1. Positive beta HCG in female of child-bearing potential defined as not post-menopausal
for 12 months or no previous surgical sterilization.

2. Active CNS disease in patient with history of CNS malignancy.

3. Patients with known allergy to bovine or murine products.

4. Patients with known history of HIV/AIDS.

5. 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.

6. Patients positive for West Nile Virus or RPR.

7. 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.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD) of T-Cell Infusions

Outcome Description:

MTD is highest dose level in which 6 patients treated with at most 2 experiencing Dose-limiting toxicity (DLT).

Outcome Time Frame:

30 days following T-Cell infusion

Safety Issue:

Yes

Principal Investigator

Elizabeth Shpall, MD

Investigator Role:

Study Director

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2010-0835

NCT ID:

NCT01362452

Start Date:

December 2012

Completion Date:

Related Keywords:

  • Leukemia
  • Lymphoma
  • Leukemia
  • Lymphoma
  • CD19-specific T cells
  • Umbilical cord blood transplantation
  • B-Lineage Lymphoid Malignancies
  • B-cell leukemia
  • Acute Lymphoblastic Leukemia
  • ALL
  • Biphenotypic Leukemia
  • Non-Hodgkin's Lymphoma
  • NHL
  • Small Lymphocytic Lymphoma
  • SLL
  • Chronic Lymphocytic Leukemia
  • CLL
  • White blood cells
  • T cells
  • Melphalan
  • Alkeran
  • Thiotepa
  • Fludarabine
  • Fludarabine Phosphate
  • Fludara
  • ATG
  • Antithymocyte Globulin
  • Thymoglobulin
  • Rituxan
  • Rituximab
  • Cyclophosphamide
  • Cytoxan
  • Neosar
  • Leukemia
  • Lymphoma

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030