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CD19-Specific T Cell Infusion in Patients With B-Lineage Lymphoid Malignancies After Allogeneic Hematopoietic Stem Cell Transplantation

Phase 1
1 Year
65 Years
Open (Enrolling)
Leukemia, Lymphoma

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Trial Information

CD19-Specific T Cell Infusion in Patients With B-Lineage Lymphoid Malignancies After Allogeneic Hematopoietic Stem Cell Transplantation

Gene Transfer:

Gene transfer involves drawing blood from a transplant donor, and then separating out the
T-cells using a machine. Researchers then perform a gene transfer to change the T-cells'
DNA, 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).

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to 1 of 4
dose levels of genetically-changed T-cells, based on when you joined this study. The first
group of participants will receive the lowest dose of T-cells, and each new group will
receive a higher dose of changed T-cells than the group before it, as long as no intolerable
side effects were seen.

Chemotherapy and HSCT:

After your donor's stem cells have been successfully collected, you will be admitted to the
hospital to receive chemotherapy and the HSCT. These procedure 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 HSCT procedure and possible risks, at
another time.

The T-cell Infusion:

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

Before the infusion, you will receive drugs to lower your risk of allergic reaction to the
T-cells. Tylenol® (acetaminophen) will be given by mouth, and Benadryl® (diphenhydramine)
may be given by mouth or by vein over a few minutes.

The T-cell infusion is given by vein, usually over 15-30 minutes. During the infusion, your
vital signs will be checked. The infusion will be divided into two parts at least 24 hours
apart. The first part of the infusion will be a much smaller part to ensure that you have no
immediate side effects.

Before the T cell infusion, you will receive drugs to lower your risk of allergic reaction
to the T cells. Acetaminophen (Tylenol®) will be given by mouth, and diphenhydramine
(Benadryl®) will be given by vein over a few minutes.

If your cancer returns after the transplant, you may receive an additional T-cell infusion.
If you receive an additional T-cell infusion, the screening tests will be repeated. The
study doctor will discuss the results of the repeated screening tests with you. If the
screening tests show that you are not eligible to receive the additional T-cell infusion,
other treatment options will be discussed with you.

Study Tests:

Within 24 hours and 3 days after the T-cell infusion, and then at 1 week, 2 weeks, 4 weeks,
8 weeks, 3 months, 6 months and 12 months after the T-cell infusion, the following tests
will be performed:

- You will have a physical exam, including measurement of your height, weight, and vital

- Your medical history will be recorded.

- Blood (about 4 tablespoons each time) 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.

- Blood (about 4 tablespoons each time) will be drawn for routine tests and tests of your
blood chemistry, blood sugars, and certain protein levels. During the Month 12 visit,
part of this blood sample will be used to check for HAMA immune system reactions.

- You will have 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 3 weeks after the transplant, more blood stem cells from the stem cell donor may
be given.

- You may need a skin biopsy or an endoscopy to check for GVHD and/or graft failure, as
well. To collect a skin biopsy, the biopsy area is numbed with anesthetic, and a small
amount of skin is collected using a needle or scalpel. An endoscopy is an exam where
you will be mildly sedated to allow a thin, flexible, lighted tube, called an
endoscope, to be inserted inside the esophagus, stomach, and first part of the small
intestine. This will allow the doctor to look for abnormal areas that might not be so
easily seen in x-rays.

Within 3 months after the T-cell infusion, you will have CT scans and/or a bone marrow
biopsy to check the status of the disease. An extra sample of bone marrow aspirate (about 2
teaspoons each time) will be drawn for research tests whenever a bone marrow aspirate/biopsy
is being done if possible. These samples will be used for research tests to study how your
immune system responds to the infusion of T-cells. To collect a bone marrow aspirate, an
area of the hip is numbed with anesthetic, and a small amount of bone marrow is withdrawn
through a large needle.

Length of Study:

You may continue taking part in this study for up to 3 months. You will be taken off study
if the disease gets worse, you have any infections, or intolerable side effects occur.

Your participation on this study will be over once you have completed the planned study
visits at 3 months after the 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.

You will be asked to sign a separate consent form for a long-term follow-up named Protocol

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

Up to 96 patients (and up to 96 donors) 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 or greater
complete remission; second or greater 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). Double hit lymphomas in first remission or more advanced
disease.Small Lymphocytic Lymphoma (SLL), or Chronic Lymphocytic Leukemia (CLL) with
progressive disease following standard therapy.

2. Age 1 to 65 years old.

3. Lansky performance score >/= 60% for patients performance 0-1 or Karnofsky greater than or equal to 80% for patients > 16 years of

4. Patient or patient's legal representative, parent(s) or guardian able to provide
written informed consent.

5. 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.

6. Patient is planned to receive an HLA-identical matched family, related haploidentical
donor (

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

2. Active grade 2-4 acute graft versus host disease (GVHD) at time of DLI.

3. Systemic corticosteroid use within 72 hours of DLI.

4. Absolute neutrophil count <500/uL at time of DLI.

5. Less than 80% donor chimerism from peripheral blood within 30 days of DLI

6. Experiencing any new Grade >2 (CTC version 4) adverse neurologic, pulmonary, cardiac,
gastrointestinal, renal or hepatic (excluding albumin) event within 24 hours prior to

7. Currently using an investigational agent at time of DLI.

8. Active infection defined as positive culture, if available, for bacteria, fungus, or
virus within a 3-day period prior to DLI and/or fever greater than 38°C within 24
hours prior to DLI.

9. Positive beta human chorionic gonadotropin (hCG) in female of child-bearing potential
defined as not post menopausal for 12 months or absence of previous surgical

10. Active Central Nervous System (CNS) disease in patients with history of CNS

11. Positive serology for HIV.

Type of Study:


Study Design:

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

Outcome Measure:

Maximum Tolerated dose (MTD) of Donor Lymphocyte Infusion (DLI)

Outcome Description:

MTD is highest dose level where 2 of 6 treated participants have dose limiting toxicity (DLT). DLT defined as new adverse event attributable to donor lymphocyte infusion (DLI) grade 3 or > involving cardiopulmonary, gastrointestinal, hepatic (excluding albumin), neurological, or renal common toxicity criteria (CTC) version 4 parameters, lasts > 3 days and possibly related to DLI within 30 days of infusion.

Outcome Time Frame:

3 months

Safety Issue:


Principal Investigator

Partow Kebriaei, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

December 2011

Completion Date:

Related Keywords:

  • Leukemia
  • Lymphoma
  • Leukemia
  • Lymphoma
  • Allogeneic donor lymphocyte infusion
  • DLI
  • Hematopoietic Stem Cell Transplantation
  • HSCT
  • Bone marrow transplant
  • CD19-specific T cells
  • T cell infusion
  • B-Lineage lymphoid malignancies
  • CD19+ lymphoid malignancies
  • Acute lymphoblastic leukemia
  • ALL
  • Biphenotypic leukemia CD19+ in advanced remission
  • Non-Hodgkin's Lymphoma
  • NHL
  • Diffuse large B-cell lymphoma
  • Small lymphocytic lymphoma
  • Follicular lymphoma
  • Mantle cell lymphoma with active disease at time of transplant
  • Leukemia
  • Lymphoma



UT MD Anderson Cancer Center Houston, Texas  77030