Leukemia, Lymphoma
Conditions
Keywords
Acute Lymphocytic Leukemia, Leukemia, Lymphoma, Burkitts Lymphoma, Lymphoblastic Leukemia, Blood Sugar, Hyperglycemia, Insulin Aspart, Insulin Glargine, Hyper-CVAD
Brief summary
The goal of this clinical research study is to learn if intense management and control of blood sugar levels during treatment for acute lymphocytic leukemia, Burkitts lymphoma, or lymphoblastic lymphoma will result in decreased risk of relapse, fewer complications, and/or longer survival.
Detailed description
High blood sugar is a common side effect of treatment for certain types of cancer. You will be randomly assigned (as in the toss of a coin) to one of two treatment groups. Participants in one group will receive blood sugar management with regular human insulin. Participants in the other group will receive more intense management with two newer forms of human insulin - insulin aspart, for rapid lowering of the blood glucose and insulin glargine for the slow decrease of blood sugar level over 24 hours. You will receive additional blood tests (about 1 tablespoon each) at the time of entry on the study and after about every 2 to 4 courses of chemotherapy while on the study. These blood tests help better define the severity of your high blood sugar and your body's ability to metabolize sugar. Any bone marrow and blood samples that were collected before your therapy for your leukemia may be used for lab tests to measure markers of glucose metabolism in the blood. You will not be required to have a bone marrow biopsy after enrollment on study. While in the hospital receiving chemotherapy, you will have your blood sugar checked 3 to 4 times a day. To check your blood sugar level, you, your nurse, or a laboratory technician will prick your finger with a small needle and place a small drop of blood on a test strip. If your blood sugar is high, you will be given the appropriate amount of insulin. Before you begin out-patient insulin treatment, a research nurse, doctor, or diabetes educator will watch how you and/or your caregiver administer your insulin shots, to make sure that it is done correctly and safely. Once you leave the hospital, you will be required to check your own blood sugar 3 times a day and take insulin (either yourself or with the help of a health provider) up to 4 times a day while on steroid therapy and for 2 days after receiving steroids. On all other days you will be required to check your blood glucose once or twice a day and administer insulin 1 - 3 times daily. You will also need to speak with a nurse by phone every 1-3 days for review of blood sugar measurements and possible adjustment of the dose of insulin you must take. You will remain on the study from the time you are found to have high blood sugar levels until completion of your chemotherapy (about 8 months for most patients). You may be taken off this study at any time if you find that you are unable or unwilling to monitor your glucose or receive insulin shots at home. You will be followed for high blood sugar levels while you are receiving treatment with Hyper-CVAD chemotherapy regimen (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating cycles with methotrexate, cytarabine, methylprednisolone). If you continue to have high blood sugar after completion of this treatment, you will have continued follow-up either with your primary physician at home or if you choose, in the Internal Medicine Clinic at M. D. Anderson. This is an investigational study. All of the insulin used in this study is FDA approved for the treatment of high blood sugar and commercially available. A total of up to 114 patients will take part in this study. All will be enrolled at M. D. Anderson.
Interventions
DRUGInsulin Glargine
Use of human insulin glargine for slow decrease of blood sugar level over 24 hours.
DRUGInsulin Aspart
Use of human insulin aspart for rapid lowering of the blood glucose level over 24 hours.
Sponsors
Novo Nordisk A/S
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age \>/= 15 years. 2. Previously untreated ALL, Burkitt's lymphoma, or lymphoblastic leukemia receiving induction chemotherapy with hyper-CVAD or variants of the hyper-CVAD regimen. 3. Random serum glucose \>/= 180 mg/dL detected during the first 2 cycles of chemotherapy and confirmed with a second measurement.
Exclusion criteria
1. History of Type I diabetes mellitus. 2. Pregnancy or breast feeding. 3. Allergy to insulin or insulin products. 4. On-going treatment of steroid-induced hyperglycemia by an endocrinologist and/or general internist.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 1-Year Overall Survival Rate | 1 year | The overall survival rate defined as percentage of participants in each treatment group who are still alive at 12 months. |
| Overall Survival | Baseline (date of randomization) to date of death or last follow-up (weekly during treatment then every 2 months post study treatment) up to 6 years | Overall survival (OS) defined as the interval between the date of randomization and the date of death. Calculation of period was from baseline (date of randomization) to the death or last follow-up. |
| Progression Free Survival (PFS) | Date of complete remission to disease progression, assessed for approximately 6 years | PFS was defined as the time interval between the date of complete remission and the date of relapse detection or death. Complete Remission (CR) defined as granulocyte count \>1.0 × 10\^9/L, platelet count \>100 × 10\^9/L, no abnormal peripheral blasts, and \<5% blasts in normocellular or hypercellular bone marrow. |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: 04/27/2004 through 7/1/2008. All participants recruited at the University of Texas (UT) MD Anderson Cancer Center.
Pre-assignment details
Fifty-two participants were randomized to a conventional treatment arm or an intensive insulin intervention arm. One participant on the conventional control arm was excluded and did not receive allocated intervention.
Participants by arm
| Arm | Count |
|---|---|
| Conventional Care Control Group: Conventional care using blood sugar management with regular human insulin. | 25 |
| Intensive Insulin Intervention Group: Intense blood sugar management with Insulin Aspart + Insulin Glargine | 26 |
| Total | 51 |
Baseline characteristics
| Characteristic | Conventional Care | Intensive Insulin | Total |
|---|---|---|---|
| Age, Continuous | 46 years | 57.5 years | 52 years |
| Region of Enrollment United States | 25 participants | 26 participants | 51 participants |
| Sex: Female, Male Female | 9 Participants | 12 Participants | 21 Participants |
| Sex: Female, Male Male | 16 Participants | 14 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 25 | 0 / 26 |
| serious Total, serious adverse events | 9 / 25 | 10 / 26 |
Outcome results
Primary
1-Year Overall Survival Rate
The overall survival rate defined as percentage of participants in each treatment group who are still alive at 12 months.
Time frame: 1 year
Population: There were 51 evaluable participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Conventional Care | 1-Year Overall Survival Rate | 80.8 percentage of participants |
| Intensive Insulin | 1-Year Overall Survival Rate | 63.5 percentage of participants |
Primary
Overall Survival
Overall survival (OS) defined as the interval between the date of randomization and the date of death. Calculation of period was from baseline (date of randomization) to the death or last follow-up.
Time frame: Baseline (date of randomization) to date of death or last follow-up (weekly during treatment then every 2 months post study treatment) up to 6 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Conventional Care | Overall Survival | 44 Months |
| Intensive Insulin | Overall Survival | 62.2 Months |
Primary
Progression Free Survival (PFS)
PFS was defined as the time interval between the date of complete remission and the date of relapse detection or death. Complete Remission (CR) defined as granulocyte count \>1.0 × 10\^9/L, platelet count \>100 × 10\^9/L, no abnormal peripheral blasts, and \<5% blasts in normocellular or hypercellular bone marrow.
Time frame: Date of complete remission to disease progression, assessed for approximately 6 years
Population: There were 51 evaluable participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Conventional Care | Progression Free Survival (PFS) | 38.8 Months |
| Intensive Insulin | Progression Free Survival (PFS) | 24 Months |