AML
Conditions
Keywords
AML
Brief summary
This research study is evaluating how a drug called lenalidomide, given in combination with the standard chemotherapy regimen of Mitoxantrone, Etoposide, and Cytarabine, commonly referred to as MEC, works in individuals with either relapsed or refractory AML
Detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. Investigational means that the intervention is being studied. The FDA (the U.S. Food and Drug Administration) has not approved lenalidomide for this specific disease, but it has been approved for other uses, including for patients with multiple myeloma and some patients with myelodysplastic syndrome. This treatment is investigational because it is not approved by the FDA for patients with AML. Lenalidomide is a chemotherapy that also modulates the immune system, and is in a category of drugs called immunomodulatory drugs or IMIDs. Some research studies suggest that lenalidomide may be effective in patients with AML. Since the investigators know that many patients who receive MEC chemotherapy alone have less than desired response rates and overall shorter periods of remission (time free from leukemia) after treatment, the investigators are studying whether the addition of lenalidomide to MEC improves upon typical responses. The combination of MEC (mitoxantrone, etoposide, and cytarabine) is a standard treatment option, commonly used for relapsed or refractory acute myeloid leukemia. .
Interventions
DRUGEtoposide
A Drug that interfere with the action of topoisomerase enzymes (topoisomerase I and II). Topoisomerase enzymes control the manipulation of the structure of DNA necessary for replication.
DRUGCytarabine
Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA.
DRUGLenalidomide
It may act by inhibiting the growth of new blood vessels (angiogenesis) in tumors, enhancing the status of the immune system, or decreasing cytokine and growth factor production
DRUGMitoxantrone
It interfere with cell reproduction
Sponsors
Celgene
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Acute myelogenous leukemia diagnosed by WHO criteria with one of the following (patients with biphenotypic leukemia are eligible, provided that the treating physician determines an AML treatment regimen is appropriate) * Primary refractory disease following \> 1cycle of chemotherapy, (such as hypomethylating agent or induction chemotherapy) * First relapse or higher. Patients with primary or secondary acute myelogenous leukemia are eligible. * Age 18-70 years old * LVEF \> 50 % * ECOG Performance status 0-2 * Able to adhere to study schedule and other protocol requirements. * Participants must have normal organ function as defined below, unless felt due to underlying disease and approved by the overall PI. Patients with Gilbert's disease may have total bilirubin up to \< 3 x ULN. * Creatinine \< 2.0mg/dl * Total bilirubin \< 1.5 x ULN * AST (SGOT) and ALT (SGPT) \< 3 x ULN. * Patients may receive hydroxyurea, steroids, or leukapheresis as necessary until Day 5 of treatment. * Patients must give voluntary written informed consent and HIPAA authorization before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. * Patients may have had prior treatment for MDS or AML, including prior lenalidomide for MDS or AML or another condition. * Patient may have had prior autologous or allogeneic transplant (family member, unrelated donor, or cord blood) if there is at least 90 days between transplant and study entry. * Patients may also have had donor lymphocyte infusion if there is at least 60 days between donor lymphocyte infusion and study entry. * Patients on immunosuppression are also eligible. * Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL prior to receiving treatment with 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 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. * Ability to understand and the willingness to sign a written informed consent document. * All study participants must be registered into the mandatory Revlimid REMS ® program, and be willing and able to comply with the requirements of the REMs ® program. Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program
Exclusion criteria
* Known hypersensitivity to thalidomide or lenalidomide (if applicable). * The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs. * Known seropositive for human immunodeficiency virus (HIV). HIV testing is not required. Hepatitis testing is not required. * Patients who have had a myocardial infarction within 6 months of enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. * Any serious medical condition laboratory abnormality or psychiatric illness that would prevent the subject from signing the consent form. * Any condition, including laboratory abnormalities, that in the opinion of the investigator places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. * Patients with major surgery within 28 days prior to treatment. * Patients with any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol. * Patient has received an investigational agent or cytotoxic chemotherapy (excluding hydroxyurea) within 7 days of study entry. * Patients with acute promyelocytic leukemia. * Females who are pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate | up to 45 days | Percentage of patients who have achieve CR or CRp after treatment. * Morphologic Complete Remission (CR): Defined as morphologic leukemia-free state, including \<5% blasts in Bone Marrow aspirate with marrow spicules, no persistent extramedullary disease, ANC \>1000/mm3 and platelet count \>100,000/mm3. * Morphologic Complete Remission without platelet recovery (CRp): Defined as CR with the exception of platelet count \< 100,000/mm3 (CRp). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients That Achieved Platelet Recovery | up to 45 days | The number of patients that achieved a stable platelet count \> 20,000/mm3 for 3 days within 45 days of starting treatment |
| Treatment-related Mortality | 50 days | Cumulative number of deaths not related to persistent or relapsed leukemia during treatment within 50 days of the start of treatment. |
| Number of Patients That Achieved ANC Recovery | up to 45 days | The number of patients that achieved a neutrophil count of \> 500/mm3 for 3 days within 45 of starting treatment |
| Overall Survival | Up to 3 years | Overall survival is defined as time from diagnosis of disease until date of death or censored on the last known date alive if patients are still alive. |
| Relapse-Free Survival | Up to 3 years | Relapse-Free Survival is defined as time from diagnosis of disease until date of relapse, death, or censored on the last known date alive if patients are still alive.Relapse is defined by morphological evidence of the original malignancy consistent with pre-treatment features. |
| Transfusion Support: Number of Red Blood Cell and Platelet Transfusions | 50 days | Number of red blood cell and platelet transfusions received within the first 50 days of treatment |
Countries
United States
Participant flow
Pre-assignment details
One patient came off study prior to receiving any treatment and was replaced. A total of 40 patients received study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Lenalidomide and MEC chemotherapy Lenalidomide is taken orally on a daily basis days 1-10. Mitoxantrone, Etoposide, and Cytarabine are administered intravenously on a daily basis for days 4 through 8 of the treatment. There is only one cycle of treatment in this study.
Etoposide: A Drug that interfere with the action of topoisomerase enzymes (topoisomerase I and II). Topoisomerase enzymes control the manipulation of the structure of DNA necessary for replication.
Cytarabine: Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA.
Lenalidomide: It may act by inhibiting the growth of new blood vessels (angiogenesis) in tumors, enhancing the status of the immune system, or decreasing cytokine and growth factor production
Mitoxantrone: It interfere with cell reproduction | 40 |
| Total | 40 |
Baseline characteristics
| Characteristic | Lenalidomide and MEC chemotherapy | — |
|---|---|---|
| Age, Continuous | 56 years | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 40 Participants | — |
| Sex: Female, Male Female | 17 Participants | — |
| Sex: Female, Male Male | 23 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 15 / 40 |
| other Total, other adverse events | 40 / 40 |
| serious Total, serious adverse events | 19 / 40 |
Outcome results
Primary
Complete Response Rate
Percentage of patients who have achieve CR or CRp after treatment. * Morphologic Complete Remission (CR): Defined as morphologic leukemia-free state, including \<5% blasts in Bone Marrow aspirate with marrow spicules, no persistent extramedullary disease, ANC \>1000/mm3 and platelet count \>100,000/mm3. * Morphologic Complete Remission without platelet recovery (CRp): Defined as CR with the exception of platelet count \< 100,000/mm3 (CRp).
Time frame: up to 45 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lenalidomide and MEC chemotherapy | Complete Response Rate | 19 Participants |
Secondary
Number of Patients That Achieved ANC Recovery
The number of patients that achieved a neutrophil count of \> 500/mm3 for 3 days within 45 of starting treatment
Time frame: up to 45 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lenalidomide and MEC chemotherapy | Number of Patients That Achieved ANC Recovery | 25 Participants |
Secondary
Number of Patients That Achieved Platelet Recovery
The number of patients that achieved a stable platelet count \> 20,000/mm3 for 3 days within 45 days of starting treatment
Time frame: up to 45 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lenalidomide and MEC chemotherapy | Number of Patients That Achieved Platelet Recovery | 27 Participants |
Secondary
Overall Survival
Overall survival is defined as time from diagnosis of disease until date of death or censored on the last known date alive if patients are still alive.
Time frame: Up to 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenalidomide and MEC chemotherapy | Overall Survival | 16 Months |
Secondary
Relapse-Free Survival
Relapse-Free Survival is defined as time from diagnosis of disease until date of relapse, death, or censored on the last known date alive if patients are still alive.Relapse is defined by morphological evidence of the original malignancy consistent with pre-treatment features.
Time frame: Up to 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenalidomide and MEC chemotherapy | Relapse-Free Survival | 13.1 months |
Secondary
Transfusion Support: Number of Red Blood Cell and Platelet Transfusions
Number of red blood cell and platelet transfusions received within the first 50 days of treatment
Time frame: 50 days
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lenalidomide and MEC chemotherapy | Transfusion Support: Number of Red Blood Cell and Platelet Transfusions | Platelet Transfusions | 7 Number of Transfusions |
| Lenalidomide and MEC chemotherapy | Transfusion Support: Number of Red Blood Cell and Platelet Transfusions | Red Blood Cell Transfusions | 9 Number of Transfusions |
Secondary
Treatment-related Mortality
Cumulative number of deaths not related to persistent or relapsed leukemia during treatment within 50 days of the start of treatment.
Time frame: 50 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lenalidomide and MEC chemotherapy | Treatment-related Mortality | 2 Participants |