Amyloidosis, Leukemia
Conditions
Brief summary
This open-label trial will evaluate the use of lenalidomide; melphalan; and dexamethasone (MDR) to treat newly diagnosed or relapsed AL amyloidosis, over the course of nine 28-day cycles.
Detailed description
The study will evaluate the 3-drug combination of lenalidomide; melphalan; and dexamethasone (MDR) as the absence of disease progression or toxicity, patients will complete nine 28-day cycles of MDR therapy, with the option of continuing treatment with lenalidomide as single-agent. Patients received up to nine cycles of treatment, with the option to continue on lenalidomide as a single agent if they responded to treatment.
Interventions
DRUGLenalidomide
Lenalidomide is a a derivative of thalidomide. Orally-administered lenalidomide 10 mg will be taken daily on days 1 to 21 of 28-day cycle.
DRUGMelphalan
Melphalan is a phenylalanine derivative of mechlorethamine. Orally-administered melphalan 0.18 mg/kg will be taken on days 1 to 4 of a 28-day cycle
DRUGDexamethasone
Dexamethasone is an anti-inflammatory and immunosuppressant steroid medication. Orally-administered dexamethasone 40 mg orally once weekly of a 28-day cycle
Sponsors
Celgene Corporation
Stanford University
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
* Newly diagnosed or relapsed AL amyloidosis * Biopsy-proven amyloidosis with evidence of an underlying plasma cell dyscrasia * abnormal clonal dominance of plasma cells in the bone marrow * detection of a monoclonal gammopathy by immunofixation electrophoresis of serum and/or urine * an abnormal serum free light chain or ratio, or AL fibrils seen on biopsy) * Measurable disease defined by an abnormal serum-free light chain or monoclonal protein by immunofixation * proteinuria ≥ 0.5 g/day, cardiac involvement with interventricular septal thickness ≥ 15 mm * hepatomegaly in the absence of congestive heart failure with elevated alkaline phosphatase * Age ≥ 18 years at the time of signing the informed consent form. * All previous cancer therapy must have been discontinued at least 4 weeks prior to treatment in this study * ECOG performance status of ≤ 3 at study entry * Laboratory test results: * Absolute neutrophil count ≥ 1.0 x 10e9 / L * Platelet count ≥ 75 x 10e9 / L * Creatinine clearance ≥ 15 mL/ minute * Total bilirubin ≤ 2-fold upper limits of normal * Disease-free of prior malignancies (excluding multiple myeloma) for ≥ 3 years with exception of: * currently treated basal cell * squamous cell carcinoma of the skin * carcinoma in situ of the cervix or breast. * Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test * Females of childbearing potential must either: * commit to continued abstinence from heterosexual intercourse * acceptable methods of birth control and 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 * All study participants must be registered into the mandatory RevAssist program, and able to comply with its requirements * Able to take aspirin (81 mg) daily • Understand and voluntarily sign an informed consent form * Able to adhere to the study visit schedule and other protocol requirements
Exclusion criteria
* Any serious medical condition that would prevent the subject from signing the informed consent form * Pregnant * breast-feeding females * Use of any other experimental drug or therapy within 28 days of baseline * Known hypersensitivity to thalidomide * Erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs * Any prior use of lenalidomide * Concurrent use of other anti-cancer agents or treatments * Known positivity for human immunodeficiency virus HIV)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hematologic Response Rate | 8 weeks | At the end of each treatment cycle (4 weeks), hematologic response rate as assessed. Hematologic response was considered to be amyloid complete response (normal FLC ratio and negative serum and urine immunofixation); very good partial response (difference between involved and uninvolved FLCs \[dFLC\] \< 40 mg/L); or partial response (dFLC decrease \> 50%). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 12 months | Participants alive 12 months after starting MDR treatment. |
| Event-free Survival (EFS) | 12 months | Assessed as the median value for EFS 12 months after starting MDR treatment |
| Duration of Response | 32 months | Assessed as the median value for the time from first partial response until progression; death; or last follow-up. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lenalidomide, Melphalan and Dexamethasone (MDR) The 3-drug combination of orally-administered lenalidomide; melphalan; and dexamethasone (MDR) will be administered as nine 28-day cycles, with the option of continuing treatment with lenalidomide as single-agent. | 25 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Enrollment and Pre-treatment | Death/ lost to follow up | 1 |
| On-treatment | Early prog disease/ death | 10 |
Baseline characteristics
| Characteristic | Lenalidomide, Melphalan and Dexamethasone (MDR) |
|---|---|
| Age, Continuous | 67 years |
| ECOG Performance Status (PS) ECOG PS 1 | 12 participants |
| ECOG Performance Status (PS) ECOG PS 2 | 9 participants |
| ECOG Performance Status (PS) ECOG PS 3 | 4 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Hematologic disease burden Kappa free light chain (%) | 20 Percentage of participants |
| Hematologic disease burden Lambda free light chain (%) | 80 Percentage of participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 23 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 23 / 25 |
| serious Total, serious adverse events | 19 / 25 |
Outcome results
Primary
Hematologic Response Rate
At the end of each treatment cycle (4 weeks), hematologic response rate as assessed. Hematologic response was considered to be amyloid complete response (normal FLC ratio and negative serum and urine immunofixation); very good partial response (difference between involved and uninvolved FLCs \[dFLC\] \< 40 mg/L); or partial response (dFLC decrease \> 50%).
Time frame: 8 weeks
Population: Subjects completing at least one full cycle of study treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lenalidomide, Melphalan and Dexamethasone (MDR) | Hematologic Response Rate | Complete Response (CR) | 2 participants |
| Lenalidomide, Melphalan and Dexamethasone (MDR) | Hematologic Response Rate | Very good Partial Response (VGPR) | 4 participants |
| Lenalidomide, Melphalan and Dexamethasone (MDR) | Hematologic Response Rate | Partial Response (PR) | 8 participants |
| Lenalidomide, Melphalan and Dexamethasone (MDR) | Hematologic Response Rate | No Response (NR) | 9 participants |
| Lenalidomide, Melphalan and Dexamethasone (MDR) | Hematologic Response Rate | Response not evaluable | 1 participants |
Secondary
Duration of Response
Assessed as the median value for the time from first partial response until progression; death; or last follow-up.
Time frame: 32 months
Population: All participants who achieved at least a partial response (9 subjects were not included due to not having any response)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenalidomide, Melphalan and Dexamethasone (MDR) | Duration of Response | 9.1 months |
Secondary
Event-free Survival (EFS)
Assessed as the median value for EFS 12 months after starting MDR treatment
Time frame: 12 months
Population: All participants starting MDR treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenalidomide, Melphalan and Dexamethasone (MDR) | Event-free Survival (EFS) | 3.15 months |
Secondary
Overall Survival (OS)
Participants alive 12 months after starting MDR treatment.
Time frame: 12 months
Population: All subjects receiving MDR treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lenalidomide, Melphalan and Dexamethasone (MDR) | Overall Survival (OS) | 58 percentage of participants |