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Phase I Study of Adoptive Transfer of Autologous T Lymphocytes Engrafted With a Chimeric Antigen Receptor Targeting the Kappa Light Chain of Immunoglobulin Expressed in Patients With Chronic Lymphocytic Leukemia, B-Cell Lymphoma or Multiple Myeloma


Phase 1
18 Years
65 Years
Open (Enrolling)
Both
Lymphoma, Myeloma, Leukemia

Thank you

Trial Information

Phase I Study of Adoptive Transfer of Autologous T Lymphocytes Engrafted With a Chimeric Antigen Receptor Targeting the Kappa Light Chain of Immunoglobulin Expressed in Patients With Chronic Lymphocytic Leukemia, B-Cell Lymphoma or Multiple Myeloma


To get the kappa antibody (with CD28) to attach to the surface of the T cell, we inserted
the antibody gene into the T cell. This is done with a virus called a retrovirus that has
been made for this study and will carry the antibody gene into the T cell. This virus also
helps us find the T cells in the patient's blood after we inject them. Because the patient
has received cells with a new gene in them patients will be followed for a total of 15 years
to see if there are any long term side effects of gene transfer.

When you enroll on this study, patients will be assigned to one of three groups of different
doses receiving kappa-CD28 T cells.

Several studies suggest that the infused T cells need room to be able to grow and accomplish
their functions and that this may not happen if there are too many other T cells in
circulation. Because of that, if the level of circulating T cells is relatively high or the
patient has B-CLL, the patient may receive one treatment of cyclophosphamide four to seven
days prior to the infusion of the T cells. This drug will decrease the numbers of the
patients own T cells before we infuse the kappa-CD28 T cells. Although we do not expect any
effect on the tumor with the dose that the patient will receive, this drug is part of many
regimens that are used to treat lymphoma, MM or CLL.

Patients will be given an injection of cells into the vein through an IV line at the
assigned dose. If you were given cyclophosphamide as stated above, the T-cells will be given
4-7 days after the cyclophosphamide. If the patient has recently received other
chemotherapy, the T-cells will be given at least 4 days after the last chemotherapy. We
would prefer that patients not receive other chemotherapy until 6 weeks after the cell
infusion but they can do so if their doctor thinks it is medically necessary. If the patient
recently had a stem cell transplant, the T-cells will be given 14-60 days after the
transplant. Before the patient receives the injection, they will be given a dose of Benadryl
and Tylenol. The injection will take about 20 minutes. We will follow the patient in the
clinic after the injection for up to 3 hours. The treatment will be given by the Center for
Cell and Gene Therapy at Texas Childrens Hospital or The Methodist Hospital.

If after a 4-6 week evaluation period after the infusion, the patient seems to be
experiencing a benefit (confirmed by radiological studies, physical exam and/or symptoms),
the patient may be able to receive up to three additional doses of the T cells if they wish.
These additional infusions would be at least 4-6 weeks apart and at the same dose level they
received the first time or a lower dose.

Medical tests before treatment—

- Before being treated, the patient will receive a series of standard medical tests:

- Physical exam

- Blood tests to measure blood cells, kidney and liver function

- Measurements of the tumor by scans and/or bone marrow studies (to include a chest x ray
at pre-infusion if not already done)

Medical tests during and after treatment—

Patients will receive standard medical tests when they are getting the infusions and after:

- Physical exams

- Blood tests to measure blood cells, kidney and liver function

- Measurements of the tumor by scans and/or bone marrow studies 6 weeks after the
infusion

To learn more about the way the kappa-CD28 chimeric receptor T cells working and how long
they last in the body, extra blood will be drawn. The total amount on any day is about 10
teaspoons. This volume is considered safe, but may be decreased if the patient is anemic.

Inclusion Criteria


INCLUSION CRITERIA:

- Eligibility Criteria for BLOOD PROCUREMENT:

- B-CLL or recurrent or refractory B-cell lymphoma (or other B-cell neoplasm) and
Multiple Myeloma (MM) or multiple myeloma monoclonal for Kappa-light chain

- Life expectancy of at least 12 weeks or greater.

- No history of other cancer (except non-melanoma skin cancer or in situ breast cancer
or cervix cancer) unless the tumor was successfully treated with curative intent at
least 2 years before trial entry

- If requires pheresis to collect blood, Cre and AST less than 1.5 upper limit of
normal

- If requires pheresis to collect blood, PT and PTTK less than 1.5 upper limit normal

ELIGIBILITY CRITERIA FOR T CELL TREATMENT:

Diagnosis of B-CLL monoclonal for Kappa light chain with one of the following criteria:

1. Evidence of progressive marrow failure as manifested by the development of, or
worsening of, anemia and/or thrombocytopenia

2. Massive (ie, at least 6 cm below the left costal margin) or progressive or
symptomatic splenomegaly

3. Massive nodes (ie, at least 10 cm in longest diameter) or progressive or symptomatic
lymphadenopathy

4. Progressive lymphocytosis with an increase of more than 50% over a 2-month period or
lymphocyte doubling time (LDT) of less than 6 months.

5. Constitutional symptoms, defined as any one or more of the following disease-related
symptoms or signs:

1. Unintentional weight loss of 10% or more within the previous 6 months;

2. Significant fatigue (ie, ECOG PS 2 or worse; inability to work or perform usual
activities);

3. Fevers higher than 100.5°F or 38.0°C for 2 or more weeks without other evidence
of infection; or

4. Night sweats for more than 1 month without evidence of infection.

5. Patients who have resistant disease after primary treatment

6. Patients who have a short time to progression after the first treatment (less
than 2 years)

OR

-Indolent or aggressive B-cell lymphoma (or other B-cell neoplasm) monoclonal
for Kappa-light chain with measurable disease after receiving at least one
chemotherapy regimen that includes Rituximab or an equivalent monoclonal
antibody

OR

- Multiple myeloma monoclonal for Kappa-light chain with measurable disease
after receiving at least one chemotherapy regimen

- Life expectancy of at least 12 weeks or greater.

- Recovered from the toxic effects of all prior chemotherapy before entering
this study.

- ANC > 500, HgB > 8.0.

- Bilirubin less than 3 times the upper limit of normal.

- AST less than 5 times the upper limit of normal.

- Serum creatinine less than 3 times upper limit of normal.

- Pulse oximetry of > 90% on room air

- Karnofsky score of > 60%.

Negative serology for HIV.

- Available autologous transduced peripheral blood T-cells with 15% or more
expression of CAR-Kappa determined by flow-cytometry.

- Patients must sign an informed consent indicating that they are aware this
is a research study and have been told of its possible benefits and toxic
side effects. Patients will be given a copy of the consent form.

- Sexually active patients must be willing to utilize one of the more
effective birth control methods during the study and for 3 months after the
study is concluded. The male partner should use a condom.

- If patient has CLL, must have negative Coombs test.

EXCLUSION CRITERIA:

BLOOD PROCUREMENT:

- Active infection requiring antibiotics

- Active autoimmune disease

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Evaluate safety of auto T cells genetically modified to express chimeric antigen receptors targeting the kappa-light chain of human immunoglobulin in pts with CLL, B cell non-Hodgkin Lymphoma or Multiple Myeloma whose tumors express Kappa-light chain.

Outcome Time Frame:

6 weeks

Safety Issue:

Yes

Principal Investigator

Carlos Ramos, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Baylor College of Medicine/Texas Children's Hospital

Authority:

United States: Food and Drug Administration

Study ID:

H-23574-CHARKALL

NCT ID:

NCT00881920

Start Date:

July 2009

Completion Date:

July 2030

Related Keywords:

  • Lymphoma
  • Myeloma
  • Leukemia
  • Lymphocytic
  • Leukemia
  • B Cell
  • Non-Hodgkin
  • Multiple Myeloma
  • Lymphoma
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Lymphoma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Lymphoma, B-Cell
  • Leukemia, B-Cell

Name

Location

Texas Children's HospitalHouston, Texas  
The Methodist HospitalHouston, Texas  77030