A Phase II Study of CC-5013 in Myelofibrosis
Study Details
Study Description
Brief Summary
The goal of this clinical research study is to learn if CC-5013 (lenalidomide) can help to control myelofibrosis. The safety of lenalidomide in the treatment of myelofibrosis will also be studied.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
Lenalidomide blocks the activity of a substance in the blood called tumor necrosis factor alpha. Tumor necrosis factor alpha is a substance that is believed to prevent new blood cells from forming in the bone marrow. Lenalidomide is also believed to help the body's immune system fight diseases.
Before treatment starts, you will have a complete physical exam, including blood (about 3 teaspoonfuls) and urine tests. A bone marrow sample will be taken. 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a bone marrow sample, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle. An ECG (test to measure the electrical activity of the heart) may be performed.
Women who are able to have children must have a negative pregnancy test [blood (about 1 teaspoon) or urine]. These pregnancy tests must occur within 10 - 14 days and again within 24 hours before the start of lenalidomide. Women who are able to have children with regular or no menstruation must have a pregnancy test weekly for the first 28 days and then every 28 days while on therapy (including breaks in therapy); when they stop taking lenalidomide and at Day 28 after the last dose of lenalidomide. Females with irregular menstruation must have a pregnancy test weekly for the first 28 days and then every 14 days while on therapy (including breaks in therapy), when they stop taking lenalidomide and at Day 14 and Day 28 after the last dose of lenalidomide.
You are considered to be a woman who is able to have children if you are a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
You will take 2 lenalidomide capsules by mouth daily. You should swallow lenalidomide capsules whole with water at the same time each day. Do not break, chew or open the capsules. If you miss a dose of lenalidomide, take it as soon as you remember on the same day. If you miss taking your dose for the entire day, take your regular dose the next scheduled day (do NOT take double your regular dose to make up for the missed dose).
If your platelet count is less than 100,000 at the time of study enrollment, the dose will be one capsule daily. The dose may be decreased depending on side effects. The dose may be increased if needed to better control the disease. This will be decided cycle by cycle.
During treatment, you will give blood samples (about 1 tablespoon each) about every week. The tests may be repeated more frequently to check for side effects. You will need to return to
-
- Anderson monthly for the first 3 months, then at least every 3 months afterwards (while on the study) in order to be evaluated for response and tolerance to lenalidomide. Only one 28-day cycle of lenalidomide may be given to you for each cycle per month.
You may continue to receive this therapy as long as there are no severe side effects or worsening of the disease. You will be asked to keep diaries documenting when you take the capsules. You will also need to return empty medication bottles at each visit. If you have had 4 to 6 months of treatment without any evidence of benefit, you may be taken off the study.
This is an investigational study. Lenalidomide is a new drug related to the drug called thalidomide. Lenalidomide is approved by the Food and Drug Administration (FDA) for the treatment of specific types of myelodysplastic syndrome (MDS) and in combination with dexamethasone for patients with multiple myeloma (MM) who have received at least 1 prior therapy. MDS and MM are cancers of the blood. It is currently being tested in a variety of cancer conditions. In this case it is considered investigational. Up to 41 participants may take part in this study. All will be enrolled at M. D. Anderson.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CC-5013
|
Drug: CC-5013
10 mg orally (2 capsules) daily
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Efficacy of CC-5013 in Myelofibrosis [3 - 4 Months for all patients; 24 months for responders]
Response evaluation, sustained for 2 weeks: Complete Remission (Neutrophil count between 1 to 10 x 10^9/L without peripheral blasts in blood or bone marrow); Partial Hematologic Response/Partial Remission (Increase in neutrophil by 50% + above 10^9/L for neutropenia); Hematologic Improvement (increase in Neutrophil count, hemoglobin, platelet count or reduction in blood/marrow blasts) or No Response. If nine or < patients respond to therapy (response other than 'No Response'), therapy declared ineffective. However, if 11 or > patients respond to therapy, therapy considered efficacious.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Diagnosis of myelofibrosis or Philadelphia negative myeloproliferative disorder with myelofibrosis requiring therapy.
-
Disease-free of prior malignancies for greater than or equal to 2 years with exception of basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.
-
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 3.
-
Total bilirubin less than or equal to 3.0 mg/dL (unless due to tumor) and serum creatinine less than or equal to 3.0 mg/dL (unless due to tumor).
-
Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing.
-
continued from above.....Men must agree to use a condom during sexual contact with a female of child bearing potential even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
-
continued from above.....† A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
-
Signed informed consent.
Exclusion Criteria:
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Use of any other experimental drug or therapy within 28 days of therapy, except in cases with rapidly progressive disease and/or recovery from all toxicity from previous therapy (does not apply to growth factors).
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Platelet count less than 30,000.
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Known prior clinically relevant hypersensitivity reaction or desquamating rash with thalidomide.
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Prior therapy with CC-5013.
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Pregnancy, suspected pregnancy or breast feeding females.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | M.D. Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- M.D. Anderson Cancer Center
- Celgene Corporation
Investigators
- Principal Investigator: Jorge E Cortes, MD, M.D. Anderson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 2003-0648
Study Results
Participant Flow
| Recruitment Details | Recruitment Period: 7/8/04 to 2/27/09. All patients registered at the University of Texas MD Anderson Cancer Center. |
|---|---|
| Pre-assignment Detail | The maximum accrual of 41 was met. |
| Arm/Group Title | CC-5013 |
|---|---|
| Arm/Group Description | 10 mg orally daily |
| Period Title: Overall Study | |
| STARTED | 41 |
| COMPLETED | 41 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | CC-5013 |
|---|---|
| Arm/Group Description | 10 mg orally daily |
| Overall Participants | 41 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
19
46.3%
|
| >=65 years |
22
53.7%
|
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
66
|
| Sex: Female, Male (Count of Participants) | |
| Female |
18
43.9%
|
| Male |
23
56.1%
|
| Region of Enrollment (participants) [Number] | |
| United States |
41
100%
|
Outcome Measures
| Title | Efficacy of CC-5013 in Myelofibrosis |
|---|---|
| Description | Response evaluation, sustained for 2 weeks: Complete Remission (Neutrophil count between 1 to 10 x 10^9/L without peripheral blasts in blood or bone marrow); Partial Hematologic Response/Partial Remission (Increase in neutrophil by 50% + above 10^9/L for neutropenia); Hematologic Improvement (increase in Neutrophil count, hemoglobin, platelet count or reduction in blood/marrow blasts) or No Response. If nine or < patients respond to therapy (response other than 'No Response'), therapy declared ineffective. However, if 11 or > patients respond to therapy, therapy considered efficacious. |
| Time Frame | 3 - 4 Months for all patients; 24 months for responders |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to treat: After a total of 41 patients were enrolled in study, nine or more patients responded to the therapy, therapy declared effective. |
| Arm/Group Title | CC-5013 |
|---|---|
| Arm/Group Description | 10 mg orally daily |
| Measure Participants | 41 |
| Complete Remission |
7
17.1%
|
| Partial Remission |
9
22%
|
| Hematologic Improvement |
12
29.3%
|
| No Response |
9
22%
|
Adverse Events
| Time Frame | 1 year and 2 months. | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | CC-5013 | |
| Arm/Group Description | 10 mg orally daily | |
All Cause Mortality |
||
| CC-5013 | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| CC-5013 | ||
| Affected / at Risk (%) | # Events | |
| Total | 15/41 (36.6%) | |
| Cardiac disorders | ||
| Edema | 1/41 (2.4%) | 1 |
| Tachycardia | 1/41 (2.4%) | 1 |
| Gastrointestinal disorders | ||
| Nausea | 1/41 (2.4%) | 1 |
| Vomiting | 1/41 (2.4%) | 3 |
| Obstruction Gastrointestinal | 1/41 (2.4%) | 1 |
| General disorders | ||
| Neutropenic fever | 1/41 (2.4%) | 1 |
| Pain | 2/41 (4.9%) | 3 |
| Disease Progression | 1/41 (2.4%) | 1 |
| Death | 1/41 (2.4%) | 1 |
| Hepatobiliary disorders | ||
| Cholecystitis | 1/41 (2.4%) | 1 |
| Infections and infestations | ||
| Infection | 1/41 (2.4%) | 1 |
| Pneumonia | 2/41 (4.9%) | 2 |
| Infection with neutropenia | 2/41 (4.9%) | 2 |
| Infection with unknown Absolute neutrophil count | 3/41 (7.3%) | 3 |
| Metabolism and nutrition disorders | ||
| Hyperglycemia | 1/41 (2.4%) | 1 |
| Nervous system disorders | ||
| Syncope, sensory neuropathy | 1/41 (2.4%) | 1 |
| Vascular disorders | ||
| Hemorrhage CNS | 1/41 (2.4%) | 1 |
| Thrombosis | 1/41 (2.4%) | 2 |
Other (Not Including Serious) Adverse Events |
||
| CC-5013 | ||
| Affected / at Risk (%) | # Events | |
| Total | 37/41 (90.2%) | |
| Blood and lymphatic system disorders | ||
| Anemia | 3/41 (7.3%) | 3 |
| Hypomagnesemia | 3/41 (7.3%) | 4 |
| Metabolic/Laboratory (other) | 6/41 (14.6%) | 6 |
| Platelets | 11/41 (26.8%) | 11 |
| Gastrointestinal disorders | ||
| Nausea | 7/41 (17.1%) | 8 |
| Vomiting | 3/41 (7.3%) | 3 |
| General disorders | ||
| pain (headache) | 2/41 (4.9%) | 3 |
| Infections and infestations | ||
| Infection | 2/41 (4.9%) | 3 |
| Neutrophils (ANC/AGC) | 14/41 (34.1%) | 14 |
| Musculoskeletal and connective tissue disorders | ||
| muscle cramps | 3/41 (7.3%) | 3 |
| Nervous system disorders | ||
| Neuropathy Sensory | 6/41 (14.6%) | 6 |
| Skin and subcutaneous tissue disorders | ||
| pruritis | 12/41 (29.3%) | 13 |
| Rash/Desquamation | 16/41 (39%) | 21 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Jorge Cortes, M.D./ Professor |
|---|---|
| Organization | The University of Texas M. D. Anderson Cancer Center |
| Phone | 713-794-5783 |
| eharriso@mdanderson.org |
- 2003-0648