Lenalidomide and Low Dose Dexamethasone Induction Therapy Followed by Low Dose Melphalan, Prednisone, Lenalidomide and Bortezomib Sequential Maintenance Therapy for Newly Diagnosed High-risk Multiple Myeloma
18 Years
N/A
Both
Multiple Myeloma
Trial Information
Lenalidomide and Low Dose Dexamethasone Induction Therapy Followed by Low Dose Melphalan, Prednisone, Lenalidomide and Bortezomib Sequential Maintenance Therapy for Newly Diagnosed High-risk Multiple Myeloma
Study design: A total of 35 patients will be accrued to this Phase II trial over a period of
about 3 years. The primary objective is to estimate the proportion of patients who are still
progression-free at 2 years. Two years will be as measured from date of registration to the
trial Progression will include disease progression as well as death due to any cause. The
Garban et al. trial found a 2-year progression-free rate of about 0.60 in 212 similar
patients. If a 2-year rate of 0.60 were to be observed in this trial, we would consider the
treatment a success. A rate of 0.60 has an exact 80% confidence interval of 0.48 - 0.71.
In section 5.1 are given the probabilities of observing a 2-year progression-free rate ≥
0.60 under different assumptions about the true rate.
Analyses: The proportion of patients progression-free at the times of full restaging (i.e.,
at 6, 12, 18, 24, 36, 48, 60, 72 months) will be calculated with 80% confidence intervals
and descriptively compared to the rates in the Garban et al. paper. Time-to-progression will
be estimated with the Kaplan-Meier method. The percentage of patients achieving a sCR, CR,
VGPR or PR, will be tabulated, and the sCR+CR+VGPR+PR disease rate will be estimated with
exact 80% confidence interval. Duration of response among patients achieving a sCR, CR,
VGPR or PR, will be defined as the length of the interval from initial response to
progression; duration of response will be tabulated. All toxicities will be tabulated by
type and grade.
Inclusion Criteria:
1. Understand and voluntarily sign an informed consent form.
2. Age 18 years or older at the time of signing the informed consent form.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Multiple myeloma diagnosed according to the following standard criteria (all three
criteria must be met):
- Monoclonal plasma cells in bone marrow ≥10% and/or presence of biopsy-proven
plasmacytoma
- Monoclonal protein present in serum and/or urine Myeloma-related organ
dysfunction (1 or more) (C) Calcium elevation in blood (serum calcium >10.5 mg/L
or ULN) (R) Renal insufficiency (SCr >2 mg/dL) (A) Anemia (hemoglobin <10 g/dL
or 2g
5. Subjects must have measurable disease requiring systemic therapy.
6. High risk multiple myeloma defined by the presence of one or more of the following:
- Deletion of chromosome 13 by metaphase analysis (standard cytogenetics) only
- deletion of 17p13 (p53) by FISH or metaphase analysis (standard cytogenetics)
- t(4;14) by FISH analysis
- t(14;16) by FISH analysis
- t(8;14) by FISH analysis
- t(14;20) by FISH analysis
- hypodiploidy detected by FISH or metaphase analysis (standard cytogenetics)
- any complex cytogenetic abnormality detected by metaphase analysis (standard
cytogenetics), with the exception of hyperdiploidy
7. Subject must not have been treated previously with any systemic therapy or radiation
therapy active against myeloma lasting more than 4 weeks duration.
8. Prior to enrollment at least 7 days must have elapsed since the date of the last
radiation or systemic treatment against myeloma.
9. ECOG performance status of less than or equal to 2 at study entry.(See Appendix 15.1)
10. All study participants must be registered into the mandatory RevAssist® program, and
be willing and able to comply with the requirements of RevAssist®.
11. 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 prescribing lenalidomide (prescriptions must be filled
within 7 days) 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.
Men must agree not to father a child and agree to use a latex*condom even if he has
had a successful vasectomy, if his partner is of child bearing potential.
12. Disease free of prior malignancies for at least 5 years with exception of currently
treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the
cervix or breast
13. Able to take 325 mg aspirin daily as prophylactic anticoagulation for the duration of
protocol related therapy to include induction and maintenance. Other appropriate
daily anticoagulation, such as warfarin or low molecular weight heparin, may be used
at physician discretion. Lenalidomide increases the risk of thrombotic events in
patients who are at high risk or with a history a thrombosis, in particular when
combined with other drugs known to cause thrombosis. When lenalidomide is combined
with other agents such as steroids (e.g. dexamethasone, prednisone), anthracyclines
(Doxil, Adriamycin) and erythropoietin the risk of thrombosis is increased.
14. Patients should receive concomitant therapy with bisphosphonates if bony lesions are
present at time of enrollment.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Evaluate the efficacy as measured by the progression free survival at 2 years
Outcome Time Frame:
2 years
Safety Issue:
No
Principal Investigator
David Rizzieri, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Duke University
Authority:
United States: Institutional Review Board
Study ID:
Pro00002869
NCT ID:
NCT00691704
Start Date:
August 2008
Completion Date:
May 2018
Related Keywords:
- Multiple Myeloma
- Multiple Myeloma
- Multiple Myeloma
- Neoplasms, Plasma Cell
Name | Location |
|---|---|
| Duke University Medical Center | Durham, North Carolina 27710 |
