A Phase I Study of PR1-Specific Cytotoxic T-Lymphocyte Infusion for Patients With Recurrent CML After Allogeneic Hematopoietic Transplantation
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N/A
Both
Chronic Myelogenous Leukemia
Trial Information
A Phase I Study of PR1-Specific Cytotoxic T-Lymphocyte Infusion for Patients With Recurrent CML After Allogeneic Hematopoietic Transplantation
Before treatment starts, you will have a complete physical exam, including blood (about 2
tablespoons) tests. You will have a chest x-ray and bone marrow will be collected. To
collect a bone marrow sample, an area of the hip or chest bone is numbed with anesthetic and
a small amount of bone marrow is withdrawn through a large needle. Women who are able to
have children must have a negative blood pregnancy test.
You will be treated with donor immune cells (T lymphocytes) that will specifically target
certain leukemia cells in your body. Each participant will receive two doses of donor cells,
60 days apart. The second dose will be given 60 days after the first dose, at a higher dose
level, as long as no serious side effects occur after the first dose and there is still
disease present. Four dose levels of PR1-specific T lymphocytes will be considered. Up to
30 patients will be treated in cohorts of 3, starting at the lowest dose level, and not
skipping an untried dose level when escalating. The trial will be stopped early if the
lowest dose level is found to be unacceptably toxic.
These cells will be given on an outpatient basis. After each donor cell infusions, you will
be followed once a week in the outpatient clinic for at least 1 month and then every 3
months for at least one year. You will have routine blood (about 2 tablespoons) and urine
tests at these visits. Participants experiencing side effects from their leukemia or
leukemia treatment may need to be hospitalized earlier.
You will also receive several other medications to help decrease the risk of infections
while your immune system is weak. These include preventative antibiotics, antiviral drugs,
and antifungal drugs.
Bone marrow samples will be taken before the second cell infusion, and then 8 weeks, 12
weeks, 6 months and 1 year after the second cell infusion.
This is an investigational study. A total of up to 30 patients will be take part in this
study. All will be enrolled at UTMDACC.
Inclusion Criteria:
1. Patients with chronic myelogenous leukemia (CML) who have previously undergone
allogeneic hematopoietic transplantation and have evidence of disease, as defined by
a,b or c (a) >5% Philadelphia chromosome positive cells on cytogenetic studies >/= 3
months post-transplant
2. (b) For patients in cytogenetic remission post-transplant, molecular evidence of
disease at any time, defined as recurrence of quantitative PCR positivity for bcr-abl
after achieving a molecular remission confirmed by 2 assays, 3 months apart or sooner
if clinically indicated; OR a >10-fold increase in the relative expression of
bcr-abl/abl detected and confirmed by a minimum of 2 consecutive PCR analysis, 3
months apart or sooner
3. (c) Molecular evidence of persistent disease on Real time PCR (bcr-abl/ abl x 100 of
0.05 and not declining) >3 months post-transplantation after treatment with imatinib
mesylate.
4. Patients must have an HLA compatible related or unrelated donor capable of donating
peripheral blood stem cells using apheresis techniques. This must be the same donor
used for the original allogeneic hematopoetic transplantation. Patient must be HLA-A2
positive
5. ECOG performance status < or = 2
6. Serum bilirubin < or = 2 mg/dl
7. Serum transaminases < 4 x normal
8. Serum creatinine < or = 2 mg/dl
9. No active uncontrolled infection
10. HIV negative
11. No acute and/or chronic GVHD requiring systemic steroid therapy
12. Patient is not pregnant or breast feeding.
13. Signed informed consent
14. Patients must be off all immunosuppressive medications for at least 2 weeks prior to
study entry.
Exclusion Criteria:
None.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximally tolerated dose of donor PR1-specific cytotoxic T-lymphocytes (PR1-CTL)
Outcome Time Frame:
Continuous reassessment, infusion day 0 and second infusion day 60+/- 7
Safety Issue:
Yes
Principal Investigator
Muzaffar H. Qazilbash, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
UT MD Anderson Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
2003-0564
NCT ID:
NCT00866346
Start Date:
March 2008
Completion Date:
Related Keywords:
- Chronic Myelogenous Leukemia
- Chronic Myelogenous Leukemia
- CML
- Allogeneic Hematopoietic Transplantation
- Bone Marrow Transplant
- PR1-Specific Cytotoxic T-Lymphocyte Infusion
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Name | Location |
|---|---|
| UT MD Anderson Cancer Center | Houston, Texas 77030 |
