Chronic Myelogenous Leukemia
Conditions
Keywords
Leukemia, Chronic Myelogenous Leukemia, CML, Imatinib, Gleevec, TALL-104
Brief summary
Objectives: * To determine the response rate and duration of response with combination of TALL-104 cells and imatinib mesylate (IM) therapy in patients with chronic myelogenous leukemia in chronic phase, that have not achieved, or have lost, adequate response to IM. * To determine the toxicity of the combination of TALL-104 cells and IM therapy in this patient population.
Detailed description
Imatinib mesylate is designed to block the enzyme that is believed to be responsible for starting the type of leukemia patient has. TALL-104 cells are cells of the immune system that have been obtained from a patient with leukemia and then processed in the laboratory to try to make them able to kill leukemia cells. If found to be eligible to take part in this study, patient will continue receiving imatinib mesylate by mouth at the same schedule and dose patient had been receiving before entering the study. Patient will receive TALL-104 cells through a needle in their vein over 1 hour on Days 1-4, and then again on Days 7, 10, 14, 17, and 21 of the cycle. The cycle will last 28 days. Blood (about 1 tablespoon) will be drawn every week for the first 4 weeks, then every 2-4 weeks for 2 months, then every 4-6 weeks until 6 months, and then every 3-6 months for routine tests and to check for any effect on organs. Patient will have follow-up visits at 1 month, 3 months, 6 months, and at least annually for 2 years, and then at least every 5 years from then on for the rest of your life. Blood (about 1 teaspoon) will be drawn to check the status of the disease. An additional 1 tablespoon will also be collected and stored to be analyzed in case unexpected side effects occur after receiving therapy. If patient experiences certain side effects, more blood may need to be drawn and more tests performed based on the side effects experienced. Up to 20 patients will take part in this study. All will be enrolled at M. D. Anderson.
Interventions
DRUGImatinib Mesylate (IM)
IM Therapy of (100 mg or 400 mg) tablets by mouth, same dose each day.
DRUGTALL-104 cells
TALL-104 cells will be given intravenously over 1 hour at the dose of 109 cells daily for 4 days, on days 1 to 4 of the cycle, and then again on days 7, 10, 14, 17 and 21 of the cycle. One cycle is equal to 28 days. Patients will receive only one cycle of therapy with TALL-104 cells
Sponsors
Abiogen Pharma
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with CML in chronic phase who have failed to achieve or have lost an adequate response to IM. For the purpose of this trial this will be defined as a lack of any cytogenetic response after 6 months of therapy or lack of major cytogenetic response after 12 months of therapy with IM. Patients that have lost their major or complete cytogenetic response will also be eligible. Patients who show a sustained increase in breakpoint cluster region gene (BCR)-Abelson gene (ABL)/ABL \[BCR-ABL/ABL\] ratio of \>/= 1-log confirmed in at least two consecutive Polymerase Chain Reaction (PCR) analyses (at least one month apart from each other) will also be eligible. 2. \*continued from above: Patients with stable molecular response defined as 2 consecutive PCR-positive results (no more than 1/2 log improvement) will also be eligible. Patients must be taking stable dose of IM for at least 3 months before study enrollment, and recovered from all toxicities related to IM, to grade 0-1. 3. Patients should be in complete or partial hematological remission, including white blood count (WBC) \</=20 x 10(9)/L, and platelets \</= 600 x 10(9)/L. 4. Eastern Cooperative Oncology Group (ECOG) scale performance status of 2 or less. 5. Age greater than 18 years of age since disease is extremely rare in younger age groups. 6. Adequate liver (total bilirubin of less than 2 times and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) of less than 2 times upper limits of normal), and renal function (creatinine of less than 2 times upper limit of normal). 7. Signed informed consent form. 8. Negative pregnancy test in women of childbearing age. 9. Negative hepatitis B and C screening blood tests.
Exclusion criteria
1. Serious intercurrent medical illnesses or active infections requiring parenteral antibiotics that would interfere with the ability of the patient to carry out the treatment program. 2. Female patients who are pregnant or breast-feeding. 3. Patients taking steroids, or those anticipated to receive steroids during the trial therapy. 4. Prior bone marrow transplant. 5. Known positivity for human immunodeficiency virus (HIV).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate (Major and Complete Cytogenetic Response) | Evaluated at baseline (pretreatment) up to 12 months | Rate is defined as number of participants with response of Major and Complete cytogenetic response out of total study participants. Response evaluated at one and 3 months from start of therapy, then every 3 months in patients with response, for one year, then every 6-12 months. Responses classified according to suppression of Philadelphia (Ph) chromosome by cytogenetic analysis: a) Complete cytogenetic response - Not Ph positive; b) Major cytogenetic response - Ph positive 1-34% of pretreatment value; c) Minor cytogenetic response - Ph positive 35-65% of pretreatment value; d) Minimal cytogenetic response - Ph positive 65-99% of pretreatment value; e) No cytogenetic response - Ph positive 100% of pretreatment value. |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: December 21, 2006 to June 27, 2008.
Participants by arm
| Arm | Count |
|---|---|
| TALL-104 + IM TALL-104 cells and imatinib mesylate (IM) therapy
Imatinib Mesylate (IM): IM Therapy of (100 mg or 400 mg) tablets by mouth, same dose each day.
TALL-104 cells: TALL-104 cells will be given intravenously over 1 hour at the dose of 109 cells daily for 4 days, on days 1 to 4 of the cycle, and then again on days 7, 10, 14, 17 and 21 of the cycle. One cycle is equal to 28 days. Patients will receive only one cycle of therapy with TALL-104 cells | 3 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | TALL-104 + IM |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Age, Continuous | 65 years |
| Region of Enrollment United States | 3 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 3 |
| serious Total, serious adverse events | 1 / 3 |
Outcome results
Primary
Response Rate (Major and Complete Cytogenetic Response)
Rate is defined as number of participants with response of Major and Complete cytogenetic response out of total study participants. Response evaluated at one and 3 months from start of therapy, then every 3 months in patients with response, for one year, then every 6-12 months. Responses classified according to suppression of Philadelphia (Ph) chromosome by cytogenetic analysis: a) Complete cytogenetic response - Not Ph positive; b) Major cytogenetic response - Ph positive 1-34% of pretreatment value; c) Minor cytogenetic response - Ph positive 35-65% of pretreatment value; d) Minimal cytogenetic response - Ph positive 65-99% of pretreatment value; e) No cytogenetic response - Ph positive 100% of pretreatment value.
Time frame: Evaluated at baseline (pretreatment) up to 12 months
Population: All three patients received the planned 9 administrations of TALL-104.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TALL-104 + IM | Response Rate (Major and Complete Cytogenetic Response) | Baseline | 0 percentage of participants |
| TALL-104 + IM | Response Rate (Major and Complete Cytogenetic Response) | 1 Month | 67 percentage of participants |
| TALL-104 + IM | Response Rate (Major and Complete Cytogenetic Response) | 3 Months | 33 percentage of participants |
| TALL-104 + IM | Response Rate (Major and Complete Cytogenetic Response) | 12 Months | 33 percentage of participants |