Carfilzomib, Lenalidomide, and Dexamethasone in New Multiple Myeloma Patients
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Blood Cancer, Hematology |
| Therapuetic Areas: | Hematology, Oncology |
| Healthy: | No |
| Age Range: | 18 - 99 |
| Updated: | 5/19/2018 |
| Start Date: | July 21, 2011 |
| End Date: | September 1, 2026 |
Carfilzomib, Lenalidomide, and Dexamethasone in Newly Diagnosed Multiple Myeloma: Clinical and Correlative Phase II Study
Background:
- Carfilzomib is an experimental anti-cancer drug that has not yet been approved for treating
multiple myeloma. Lenalidomide is a drug that may stop tumor growth and help the immune
system kill cancer cells. Dexamethasone is a drug that helps stop inflammation. It is
sometimes used to treat (alone or with other drugs) certain types of cancer, especially
multiple myeloma. This combination of drugs has not been tested in people with multiple
myeloma. Researchers want to see whether it is safe and effective for this group.
Objectives:
- To test the effectiveness of combined carfilzomib, lenalidomide, and dexamethasone in
treating multiple myeloma.
Eligibility:
- People at least 18 years of age who have multiple myeloma that has not been treated.
Design:
- Participants will be screened with a medical history and physical exam. They will also
have blood and urine tests, a bone marrow sample, and molecular imaging studies.
- Participants will have eight 28-day cycles of treatment. The combined study drugs will
be given as tablets and injections. Those in the study will be monitored with frequent
blood tests, bone marrow samples, and molecular imaging studies. In addition to current
standard measures to determine clinical responses, molecular tests will be conducted to
define evidence of minimal residual disease.
- After the first four cycles of therapy, those who are eligible for a stem cell
transplant will have stem cells collected and stored for use if the cancer returns.
- After stem cell collection, participants will have the second four treatment cycles.
-, If the disease has improved or is stable at the end of eight cycles, those in the
study may have another 12 cycles of low-dose (maintenance) lenalidomide alone.
- Participants will have regular follow-up visits after the end of the study chemotherapy.
- Carfilzomib is an experimental anti-cancer drug that has not yet been approved for treating
multiple myeloma. Lenalidomide is a drug that may stop tumor growth and help the immune
system kill cancer cells. Dexamethasone is a drug that helps stop inflammation. It is
sometimes used to treat (alone or with other drugs) certain types of cancer, especially
multiple myeloma. This combination of drugs has not been tested in people with multiple
myeloma. Researchers want to see whether it is safe and effective for this group.
Objectives:
- To test the effectiveness of combined carfilzomib, lenalidomide, and dexamethasone in
treating multiple myeloma.
Eligibility:
- People at least 18 years of age who have multiple myeloma that has not been treated.
Design:
- Participants will be screened with a medical history and physical exam. They will also
have blood and urine tests, a bone marrow sample, and molecular imaging studies.
- Participants will have eight 28-day cycles of treatment. The combined study drugs will
be given as tablets and injections. Those in the study will be monitored with frequent
blood tests, bone marrow samples, and molecular imaging studies. In addition to current
standard measures to determine clinical responses, molecular tests will be conducted to
define evidence of minimal residual disease.
- After the first four cycles of therapy, those who are eligible for a stem cell
transplant will have stem cells collected and stored for use if the cancer returns.
- After stem cell collection, participants will have the second four treatment cycles.
-, If the disease has improved or is stable at the end of eight cycles, those in the
study may have another 12 cycles of low-dose (maintenance) lenalidomide alone.
- Participants will have regular follow-up visits after the end of the study chemotherapy.
Background:
- Multiple myeloma (MM) is an incurable plasma cell neoplasm with a median survival of 3-4
years.
- Novel agent combinations with proteasome inhibitors demonstrate improved response rates
while increasing survival in MM patients.
- A common debilitating side effect of the proteasome inhibitor bortezomib is neuropathy.
- Carfilzomib is a new proteasome inhibitor with potent anti-MM effects and decreased
peripheral neuropathy
Objectives:
-Evaluate toxicity, including peripheral neuropathy, of carfilzomib, lenalidomide, and
dexamethasone (CRd) in untreated MM patients
Eligibility:
- Newly diagnosed patients with histologically confirmed multiple myeloma
- Age greater than or equal to 18 years
- Creatinine Clearance (CrCl) greater than or equal to 60 ml/min. CrCl will be calculated
using the Cockcroft- Gault method. If the calculated CrCl based on Cockcroft-Gault
method is <60 mL/min, patient will have a 24 hr urine collection to measure CrCl. The
measured CrCl must also be greater than or equal to 60 ml/min.
- Without serious co-morbidity that would interfere with receipt of CRd
- Absolute neutrophil count (ANC) greater than or equal to 1.0 K/uL, hemoglobin greater
than or equal to 8 g/dL, and platelet count greater than or equal to 75 K/uL
- Adequate hepatic function, with bilirubin less than 1.5 x the upper limit of normal
(ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than
3.0 x ULN
Design:
- Single arm, single stage phase II trial of combination therapy (carfilzomib,
lenalidomide, and dexamethasone) for untreated multiple myeloma patients with an early
stopping rule for toxicity
- Patients will receive 8 cycles of induction combination therapy of CRd
- Each cycle consists of 28-days
- After 4 cycles of therapy, transplant eligible patients will undergo stem cell
collection
- Patients achieving stable disease or better after 8 cycles of CRd will receive
lenalidomide extended dosing (phase I) for 12 cycles. After 12 cycles, patients will
have the option to continue extended dosing (phase II) for one additional year.
- Patients will have routine blood work with serum protein electrophoresis (SPEP) and free
light chains monthly
- Pre- and post-treatment bone marrow biopsies will be obtained for confirmation of
diagnosis and correlative studies
- Patients will also undergo evaluation for minimal residual disease at regular interval
time points, using multi-parametric flow cytometry and fludeoxyglucose 18F-positron
emission tomography - computed tomography (FDG PET-CT)
- A single stage phase II design will be employed, with an early stopping rule. Unless 4
or more patients in the first 20 have Grade 3 or higher neurologic toxicity in the first
2 completed cycles, a total of 45 evaluable patients will be enrolled in this study.
- Multiple myeloma (MM) is an incurable plasma cell neoplasm with a median survival of 3-4
years.
- Novel agent combinations with proteasome inhibitors demonstrate improved response rates
while increasing survival in MM patients.
- A common debilitating side effect of the proteasome inhibitor bortezomib is neuropathy.
- Carfilzomib is a new proteasome inhibitor with potent anti-MM effects and decreased
peripheral neuropathy
Objectives:
-Evaluate toxicity, including peripheral neuropathy, of carfilzomib, lenalidomide, and
dexamethasone (CRd) in untreated MM patients
Eligibility:
- Newly diagnosed patients with histologically confirmed multiple myeloma
- Age greater than or equal to 18 years
- Creatinine Clearance (CrCl) greater than or equal to 60 ml/min. CrCl will be calculated
using the Cockcroft- Gault method. If the calculated CrCl based on Cockcroft-Gault
method is <60 mL/min, patient will have a 24 hr urine collection to measure CrCl. The
measured CrCl must also be greater than or equal to 60 ml/min.
- Without serious co-morbidity that would interfere with receipt of CRd
- Absolute neutrophil count (ANC) greater than or equal to 1.0 K/uL, hemoglobin greater
than or equal to 8 g/dL, and platelet count greater than or equal to 75 K/uL
- Adequate hepatic function, with bilirubin less than 1.5 x the upper limit of normal
(ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than
3.0 x ULN
Design:
- Single arm, single stage phase II trial of combination therapy (carfilzomib,
lenalidomide, and dexamethasone) for untreated multiple myeloma patients with an early
stopping rule for toxicity
- Patients will receive 8 cycles of induction combination therapy of CRd
- Each cycle consists of 28-days
- After 4 cycles of therapy, transplant eligible patients will undergo stem cell
collection
- Patients achieving stable disease or better after 8 cycles of CRd will receive
lenalidomide extended dosing (phase I) for 12 cycles. After 12 cycles, patients will
have the option to continue extended dosing (phase II) for one additional year.
- Patients will have routine blood work with serum protein electrophoresis (SPEP) and free
light chains monthly
- Pre- and post-treatment bone marrow biopsies will be obtained for confirmation of
diagnosis and correlative studies
- Patients will also undergo evaluation for minimal residual disease at regular interval
time points, using multi-parametric flow cytometry and fludeoxyglucose 18F-positron
emission tomography - computed tomography (FDG PET-CT)
- A single stage phase II design will be employed, with an early stopping rule. Unless 4
or more patients in the first 20 have Grade 3 or higher neurologic toxicity in the first
2 completed cycles, a total of 45 evaluable patients will be enrolled in this study.
- INCLUSION CRITERIA:
- Newly diagnosed patients with histologically confirmed multiple myeloma (MM) based on
the following criteria:
1. Clonal plasma cells in the bone marrow
2. Measurable disease within the past 4 weeks defined by any one of the following:
1. Serum monoclonal protein greater than or equal to 1.0 g/dL
2. Urine monoclonal protein greater than 200 mg/24 hour
3. Serum immunoglobulin free light chain greater than 10 mg/dL AND abnormal
kappa/lambda ratio
3. Evidence of underlying end organ damage attributed to underlying plasma cell
proliferative disorder meeting at least one of the following:
1. Hypercalcemia: serum calcium greater than or equal to 2.65 mmol/L
2. Renal Insufficiency: serum creatinine greater than 2.0 mg/dL
3. Anemia: hemoglobin value less than10 g/dL or 2 g/dL less than normal
reference
4. Bone disease: lytic lesions, severe osteopenia or pathological fractures
- Creatinine Clearance (CrCl) greater than or equal to 60 ml/min. CrCl will be
calculated by Cockcroft-Gault method. CrCl (calculated) = (140 Age) x Mass (in
kilograms) x [0.85 if Female] 72 times Serum Creatinine (in mg/dL). If calculated CrCl
based on Cockcroft-Gault method is <60 mL/min, patient will have a 24 hr urine
collection to measure CrCl. The measured CrCl msut be also greater than or equal to 60
ml/min.
- Age greater than or equal to 18 years. Because no dosing or adverse event data are
currently available on the use of carfilzomib in combination with lenalidomide in
patients less than18 years of age, children are excluded from this study, but will be
eligible for future pediatric trials.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Absolute neutrophil count (ANC) greater than or equal to 1.0 K/uL, hemoglobin greater
than or equal to 8 g/dL (transfusions are permissible), and platelet count greater
than or equal to 75 K/uL
- Adequate hepatic function, with bilirubin less than 1.5 times the upper limit of
normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
less than 3.0 times ULN.
- All study participants must be able to tolerate one of the following
thromboprophylactic strategies: aspirin, low molecular weight heparin or warfarin
(coumadin).
- All study participants must be registered into the mandatory RevAssist program, and be
willing and able to comply with the requirements of RevAssist .
- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
test within 10-14 days and again within 24 hours prior to prescribing lenalidomide for
Cycle 1 (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 28 days before she starts taking lenalidomide. Females of child
bearing potential (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.
- Subjects must be able to give informed consent
EXCLUSION CRITERIA:
- Prior or concurrent systemic treatment for MM.
- Treatment of hypercalcemia or spinal cord compression or aggressively progressing
myeloma with corticosteroids is permitted.
- Bisphosphonates are permitted.
- Treatment with corticosteroids for indications other than MM is permitted.
- Radiotherapy is permitted.
- Treatment for smoldering myeloma is permitted.
- Plasma cell leukemia
- Pregnant or lactating females. Because there is a potential risk for adverse events in
nursing infants secondary to treatment of the mother with carfilzomib in combination
with lenalidomide, breastfeeding should be discontinued if the mother is treated with
carfilzomib and lenalidomide. These potential risks may also apply to other agents
used in this study.
- Uncontrolled hypertension or diabetes
- Active hepatitis B or C infection
- Has significant cardiovascular disease with New York Heart Association (NYHA) Class
III or IV symptoms, or hypertrophic cardiomyopathy, or restrictive cardiomyopathy, or
myocardial infarction within 3 months prior to enrollment, or unstable angina, or
unstable arrhythmia as determined by history and physical examination. Echocardiogram
will be performed if clinically warranted.
- Has refractory gastrointestinal (GI) disease with refractory nausea/vomiting,
inflammatory bowel disease, or bowel resection that would prevent absorption
- Uncontrolled intercurrent illness including but not limited to active infection or
psychiatric illness/social situations that would compromise compliance with study
requirements
- Significant neuropathy greater than or equal to Grade 3 at baseline
- Contraindication to any concomitant medication, including antivirals, anticoagulation
prophylaxis, tumor lysis prophylaxis, or hydration given prior to therapy
- Major surgery within 1 month prior to enrollment
- Recruitment Strategies:
- Patients that progress from the smoldering multiple myeloma (SMM) and monoclonal
gammopathy of undetermined significance (MGUS) Natural History Study (NCI
Protocol: 10-C-0096) will be potential candidates.
- Other participant sources will be from outside physician referrals.
- Our ongoing natural history study and outside physician referral network has a
high representation of minorities.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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