DS Stage III Plasma Cell Myeloma, DS Stage II Plasma Cell Myeloma, DS Stage I Plasma Cell Myeloma, Refractory Plasma Cell Myeloma
Conditions
Brief summary
This phase II trial studies lenalidomide, dexamethasone, and clarithromycin in treating patients who have undergone stem cell transplant for multiple myeloma. Biological therapies, such as lenalidomide and clarithromycin, may stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with dexamethasone and clarithromycin may be an effective treatment for multiple myeloma.
Detailed description
PRIMARY OBJECTIVES: I. Evaluate the toxicity of the use of lenalidomide/biaxin (clarithromycin)/dexamethasone as maintenance therapy after autologous/syngeneic transplant. II. Evaluate the median time to disease progression. III. Evaluate survival. OUTLINE: Patients receive clarithromycin orally (PO) twice daily (BID) and dexamethasone PO once a week. Treatment with clarithromycin and dexamethasone continues for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also receive lenalidomide PO once daily (QD) on days 1-14. Courses with lenalidomide repeat every 21 days in the absence of disease progression or unacceptable toxicity. NOTE: \*After one year of treatment, dexamethasone is tapered for an additional 4 weeks. After completion of study treatment, patients are followed up periodically.
Interventions
DRUGClarithromycin
Given Orally (PO)
DRUGDexamethasone
Given PO
DRUGLenalidomide
Given Orally (PO)
Sponsors
National Cancer Institute (NCI)
Fred Hutchinson Cancer Center
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
* Any autologous or syngeneic patient who underwent high dose melphalan (\>= 140 mg/m\^2) therapy/peripheral blood stem cell (PBSC) or bone marrow (BM) rescue for any stage of multiple myeloma and did not participate in another clinical transplant trial which is also evaluating long-term disease free survival or survival * Platelet count (transfusion independent) \> 50,000 cells/mm\^3 and absolute granulocyte count \> 1500 cells/mm\^3 for 5 calendar days after recovery from high dose therapy * Patients should be between 30 days to 120 days after transplant * Willingness and ability to comply with Food and Drug Administration (FDA)-mandated REV ASSIST Program, Celgene System for Lenalidomide Education and Prescribing Safety * Signing a written informed consent form
Exclusion criteria
* Karnofsky score less than 70 * A left ventricular ejection fraction less than 45% immediately pre transplant; patients with congestive heart disease with transplant, history of myocardial infarction (MI), or history of coronary artery disease * Total bilirubin greater than 2 mg/ml (unless history of Gilbert's disease), serum glutamic-oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) \> 2.5 x upper limit of normal * Calculated by Cockcroft-Gault formula or measured serum creatinine clearance \< 25 ml/minute * Pregnant and/or lactating females * Patients who cannot give informed consent * Patients with untreated systemic infection * Patients with history prior to transplant of treatment with combination therapy Lenalidomide/Biaxin and steroid without response * Patients allergic to lenalidomide, biaxin or dexamethasone * Referring physician not registered with REV ASSIST program or unwilling to oversee the care of the patients on study and comply with the FDA-mandated REV ASSIST Program * Patients unwilling to practice adequate forms of contraception if clinically indicated until 30 days after stopping therapy; male patients on study need to be consulted to use latex condoms (even if they have had a vasectomy) every time they have sex with a woman who is able to have children while they are being treated and for 30 days after stopping drugs * Patients with \>= grade 3 peripheral neuropathy * Prior history of uncontrollable side effects to dexamethasone therapy * A prior history of human immunodeficiency virus (HIV) positivity with pre-transplant evaluation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Episodes of Grade 3-4 Non Infectious, Non-dermatological or Non-neurological Toxicities, Episodes of Any Infections, Grade 3-4 Dermatological or Episodes of Grade 2-3 Peripheral Neuropathy Common Terminology Criteria for Adverse Events Version 3 | First year of therapy | — |
| Time to Disease Progression | Up to 10.25 years | International Myeloma Working Group Uniform Response Criteria was used |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Survival | From date of transplant until the date of death from any cause, assessed up to 10.25 years | number of patients alive or dead |
Countries
United States
Participant flow
Pre-assignment details
32 patients were enrolled. 31 patients started therapy. 1 patient was consented but was deemed ineligible prior to therapy initiation.
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Clarithromycin, Dexamethasone, Lenalidomide) Patients receive clarithromycin orally (PO) twice daily and dexamethasone PO once a week. Treatment with clarithromycin and dexamethasone continues for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also receive lenalidomide PO once daily on days 1-14. Courses with lenalidomide repeat every 21 days in the absence of disease progression or unacceptable toxicity. Lenalidomide is taken 4 hours or more after last dose of daily clarithromycin.
NOTE: \*After one year of treatment, dexamethasone is tapered for an additional 4 weeks.
Clarithromycin: Given Orally (PO)
Dexamethasone: Given PO
Lenalidomide: Given PO | 31 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 11 |
| Overall Study | Lack of Efficacy | 5 |
Baseline characteristics
| Characteristic | Treatment (Clarithromycin, Dexamethasone, Lenalidomide) |
|---|---|
| Age, Continuous | 58 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 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 | 28 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 13 / 31 |
| other Total, other adverse events | 19 / 31 |
| serious Total, serious adverse events | 11 / 31 |
Outcome results
Primary
Episodes of Grade 3-4 Non Infectious, Non-dermatological or Non-neurological Toxicities, Episodes of Any Infections, Grade 3-4 Dermatological or Episodes of Grade 2-3 Peripheral Neuropathy Common Terminology Criteria for Adverse Events Version 3
Time frame: First year of therapy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Clarithromycin, Dexamethasone, Lenalidomide) | Episodes of Grade 3-4 Non Infectious, Non-dermatological or Non-neurological Toxicities, Episodes of Any Infections, Grade 3-4 Dermatological or Episodes of Grade 2-3 Peripheral Neuropathy Common Terminology Criteria for Adverse Events Version 3 | Neutropenia | 6 episodes |
| Treatment (Clarithromycin, Dexamethasone, Lenalidomide) | Episodes of Grade 3-4 Non Infectious, Non-dermatological or Non-neurological Toxicities, Episodes of Any Infections, Grade 3-4 Dermatological or Episodes of Grade 2-3 Peripheral Neuropathy Common Terminology Criteria for Adverse Events Version 3 | Thrombocytopenia | 1 episodes |
| Treatment (Clarithromycin, Dexamethasone, Lenalidomide) | Episodes of Grade 3-4 Non Infectious, Non-dermatological or Non-neurological Toxicities, Episodes of Any Infections, Grade 3-4 Dermatological or Episodes of Grade 2-3 Peripheral Neuropathy Common Terminology Criteria for Adverse Events Version 3 | Deep venous thrombus/Pulmonary Embolism | 1 episodes |
| Treatment (Clarithromycin, Dexamethasone, Lenalidomide) | Episodes of Grade 3-4 Non Infectious, Non-dermatological or Non-neurological Toxicities, Episodes of Any Infections, Grade 3-4 Dermatological or Episodes of Grade 2-3 Peripheral Neuropathy Common Terminology Criteria for Adverse Events Version 3 | Anemia | 1 episodes |
| Treatment (Clarithromycin, Dexamethasone, Lenalidomide) | Episodes of Grade 3-4 Non Infectious, Non-dermatological or Non-neurological Toxicities, Episodes of Any Infections, Grade 3-4 Dermatological or Episodes of Grade 2-3 Peripheral Neuropathy Common Terminology Criteria for Adverse Events Version 3 | Pneumonia | 4 episodes |
| Treatment (Clarithromycin, Dexamethasone, Lenalidomide) | Episodes of Grade 3-4 Non Infectious, Non-dermatological or Non-neurological Toxicities, Episodes of Any Infections, Grade 3-4 Dermatological or Episodes of Grade 2-3 Peripheral Neuropathy Common Terminology Criteria for Adverse Events Version 3 | Upper respiratory infections | 12 episodes |
| Treatment (Clarithromycin, Dexamethasone, Lenalidomide) | Episodes of Grade 3-4 Non Infectious, Non-dermatological or Non-neurological Toxicities, Episodes of Any Infections, Grade 3-4 Dermatological or Episodes of Grade 2-3 Peripheral Neuropathy Common Terminology Criteria for Adverse Events Version 3 | Sinusitis/acute otitis media | 3 episodes |
| Treatment (Clarithromycin, Dexamethasone, Lenalidomide) | Episodes of Grade 3-4 Non Infectious, Non-dermatological or Non-neurological Toxicities, Episodes of Any Infections, Grade 3-4 Dermatological or Episodes of Grade 2-3 Peripheral Neuropathy Common Terminology Criteria for Adverse Events Version 3 | Epiglottic appendagitis | 1 episodes |
| Treatment (Clarithromycin, Dexamethasone, Lenalidomide) | Episodes of Grade 3-4 Non Infectious, Non-dermatological or Non-neurological Toxicities, Episodes of Any Infections, Grade 3-4 Dermatological or Episodes of Grade 2-3 Peripheral Neuropathy Common Terminology Criteria for Adverse Events Version 3 | Cellulitis | 3 episodes |
| Treatment (Clarithromycin, Dexamethasone, Lenalidomide) | Episodes of Grade 3-4 Non Infectious, Non-dermatological or Non-neurological Toxicities, Episodes of Any Infections, Grade 3-4 Dermatological or Episodes of Grade 2-3 Peripheral Neuropathy Common Terminology Criteria for Adverse Events Version 3 | Clostridium difficile colitis | 1 episodes |
| Treatment (Clarithromycin, Dexamethasone, Lenalidomide) | Episodes of Grade 3-4 Non Infectious, Non-dermatological or Non-neurological Toxicities, Episodes of Any Infections, Grade 3-4 Dermatological or Episodes of Grade 2-3 Peripheral Neuropathy Common Terminology Criteria for Adverse Events Version 3 | Vaginitis | 3 episodes |
| Treatment (Clarithromycin, Dexamethasone, Lenalidomide) | Episodes of Grade 3-4 Non Infectious, Non-dermatological or Non-neurological Toxicities, Episodes of Any Infections, Grade 3-4 Dermatological or Episodes of Grade 2-3 Peripheral Neuropathy Common Terminology Criteria for Adverse Events Version 3 | Peripheral neuropathy | 10 episodes |
| Treatment (Clarithromycin, Dexamethasone, Lenalidomide) | Episodes of Grade 3-4 Non Infectious, Non-dermatological or Non-neurological Toxicities, Episodes of Any Infections, Grade 3-4 Dermatological or Episodes of Grade 2-3 Peripheral Neuropathy Common Terminology Criteria for Adverse Events Version 3 | Dermal leukocytic vasculitis | 1 episodes |
| Treatment (Clarithromycin, Dexamethasone, Lenalidomide) | Episodes of Grade 3-4 Non Infectious, Non-dermatological or Non-neurological Toxicities, Episodes of Any Infections, Grade 3-4 Dermatological or Episodes of Grade 2-3 Peripheral Neuropathy Common Terminology Criteria for Adverse Events Version 3 | Secondary cancer Acute Myeloid Leukemia | 1 episodes |
| Treatment (Clarithromycin, Dexamethasone, Lenalidomide) | Episodes of Grade 3-4 Non Infectious, Non-dermatological or Non-neurological Toxicities, Episodes of Any Infections, Grade 3-4 Dermatological or Episodes of Grade 2-3 Peripheral Neuropathy Common Terminology Criteria for Adverse Events Version 3 | Re-occurrence of skin cancer | 1 episodes |
Primary
Time to Disease Progression
International Myeloma Working Group Uniform Response Criteria was used
Time frame: Up to 10.25 years
Population: Measured among the 20 patients who progressed
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Clarithromycin, Dexamethasone, Lenalidomide) | Time to Disease Progression | 30.5 months |
Secondary
Survival
number of patients alive or dead
Time frame: From date of transplant until the date of death from any cause, assessed up to 10.25 years
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Clarithromycin, Dexamethasone, Lenalidomide) | Survival | Multiple meyloma deaths | 10 Participants |
| Treatment (Clarithromycin, Dexamethasone, Lenalidomide) | Survival | Acute Myeloid Leukemia death | 1 Participants |
| Treatment (Clarithromycin, Dexamethasone, Lenalidomide) | Survival | Lung cancer death | 1 Participants |
| Treatment (Clarithromycin, Dexamethasone, Lenalidomide) | Survival | Heart attack death | 1 Participants |
| Treatment (Clarithromycin, Dexamethasone, Lenalidomide) | Survival | Alive | 18 Participants |