NCI Community Oncology Research Program - Kansas City (NCORP-KC)
NCI Community Oncology Research Program - Kansas City (NCORP-KC)




NCI Community Oncology Research Program - Protocol Summary

ECOG-ACRIN E1A11 - "Randomized Phase III Trial of Bortezomib, LENalidomide and Dexamethasone (VRd) Versus Carfilzomib, Lenalidomide and Dexamethasone (CRd) Followed by Limited or Indefinite DURation Lenalidomide MaintenANCE in Patients with Newly Diagnosed Symptomatic Multiple Myeloma (ENDURANCE)"

The summary below serves as a brief review of the treatment plan and eligibility for the protocol.


This summary is not intended to be used in place of the full eligibility & treatment information in the protocol.
 

Please contact NCORP-KC for complete protocol information.



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Myeloma Clinical Trial

CANCER TYPE: Myeloma
RESEARCH BASE: ECOG-ACRIN
NCT NUMBER: NCT01863550
HIPPA FORM: DOWNLOAD HIPPA FORM

Consent Form: VIEW CONSENT FORM
UPDATED ON 07/27/2018 (13:57:05)

BRIEF DESCRIPTION

Multiple myeloma, newly diagnosed, bortezomib, lenalidomide, and dexamethasone vs. carfilzomib, lenalidomide and dexamethazone.  DCP-001 Eligible



NOTES


Treatment         (Supplied Drugs:  Carfilzomib and Lenalidomide)

 

Step 1 Induction Treatment should start within fourteen working days after registration.

Arm A

Bortezomib:  1.3 mg/m2 SQ or IV days 1, 4, 8 and 11 Cycles 1-8

                    1.3 mg/m2 SQ or IV days 1 and 8 Cycles 9-12

Lenalidomide:  25 mg PO daily days 1-14

Dexamethasone:  20 mg PO days 1, 2, 4, 5, 8, 9, 11, 12 Cycles 1-4

                          10 mg PO days 1, 2, 4, 5, 8, 9, 11, 12 Cycles 5-8

                          10 mg PO days 1, 2, 8 and 9 Cycles 9-12

Cycle = 3 weeks

Arm B

Carfilzomib:  20 mg/m2 IV days 1 and 2; 36 mg/m2 IV days 8, 9, 15, 16 Cycle 1

                   36 mg/m2 IV days 1, 2, 8, 9, 15, 16 Cycles 2-9

Lenalidomide:  25 mg PO daily days 1-21

Dexamethasone:  40 mg PO days 1, 8, 15, 22 Cycles 1-4

                          20 mg PO days 1, 8, 15, 22 Cycles 5-9

Cycle = 4 weeks

 

Step 2 Maintenance Treatment should start within 14 working days after registration and within 42 days of completing Step 1 treatment (last day of the induction cycle).

Arm C

Lenalidomide:  15 mg PO daily days 1-21, for 24 cycles

Cycle = 4 weeks

Arm D

Lenalidomide:  15 mg PO daily days 1-21, until progression or excessive toxicity

Cycle = 4 weeks

 

 

 



ELIGIBILITY

Step 1 Randomization

  • Age ≥ 18 years.
  • Patients must be diagnosed with symptomatic standard-risk multiple myeloma (SR-MM) within 90 days prior to registration as defined by all of the following (except GEP70 status if unknown):
    • No evidence of t(14;16) by FISH testing on bone marrow or not available
    • No evidence of t(14:20) by FISH testing on bone marrow or not available
    • No evidence of deletion 17p by FISH testing on bone marrow
    • NOTE: If the FISH result states that no IgH abnormality is present, both t(14;16) and t(14;20) can be considered negative. In addition, if the patient has a t(11;14) or t(4;14) translocation present, they can be considered negative for t(14;16) and t(14;20). If testing for t(14;16) or t(14;20) could not be performed for lack of sufficient material or non-availability of the probe in the test panel, patients can be enrolled on the study.
    • Standard Risk GEP70 signature within the past 90 days (only if GEP has been done and results are available.
      NOTE: GEP testing is NOT a requirement for the study).
      If the test has been done, patients found to have a GEP70 status of High-Risk will not be eligible.
    • Serum LDH ≤ 2 x ULN within the past 28 days
    • No more than 20% circulating plasma cells on WBC differential or 2,000 plasma cells/microliter of peripheral blood within the past 90 days
  • Patients must have measurable or evaluable disease as defined by having one or more of the following, obtained within 28 days prior to randomization:
    •  ≥ 1g/dL monoclonal protein (M-protein) on serum protein electrophoresis
    •  ≥ 200 mg/24 hrs of monoclonal protein on a 24 hour urine protein electrophoresis
    • Involved free light chain ≥ 10 mg/dL or ≥ 100 g/L AND abnormal serum immunoglobulin kappa to lambda free light chain ratio (< 0.26 or > 1.65)
    • Monoclonal bone marrow plasmacytosis ≥ 30% (evaluable disease)
    • SPEP, UPEP, serum FLC assay and bone marrow biopsy and or aspirate are required to be performed within 28 days prior to randomization.
    • NOTE: UPEP (on a 24-hour collection) is required, no substitute method is acceptable. Urine must be followed monthly if the baseline urine M-spike is ≥ 200 mg/24 hr. Please note that if both serum and urine M-components are present, both must be followed in order to evaluate response.
    • NOTE: The serum free light chain test is required to be done if the patient does not have measurable disease in the serum or urine. Measurable disease in the serum is defined as having a serum M-spike ≥ 1 g/dL. Measurable disease in the urine is defined as having a urine M-spike ≥ 200mg/24 hr.
  • The following laboratory levels must be obtained within 28 days prior to randomization:
    • Hemoglobin ≥ 8 g/dL.
    • Untransfused platelet count ≥ 75,000 cells/mm3.
    • Absolute neutrophil count ≥ 1000 cells/mm3.
    • Calculated creatinine clearance ≥ 30 mL/min
    • Bilirubin ≤ 1.5 mg/dL.
    • SGPT (ALT) and SGOT (AST) < 2.5 times the upper limit of normal.
  • Patients must have received no more than one cycle (4 weeks or less) of prior chemotherapy and no more than 160mg of prior dexamethasone (or equivalent dose of prednisone) for treatment of symptomatic myeloma. They should not have been exposed to lenalidomide, bortezomib or carfilzomib for treatment of symptomatic myeloma. Prior radiation therapy to symptomatic lesions is allowed provided 14 days is allowed between the completion of radiation therapy and start of protocol treatment.
  • Prior systemic glucocorticoid use for the treatment of non-malignant disorders is permitted. Prior or concurrent topical or localized glucocorticoid therapy to treat non-malignant comorbid disorders is permitted.  NOTE: Concurrent use after registration on the study should be restricted to the equivalent of prednisone 10 mg per day.
  • Patients must not have active, uncontrolled seizure disorder. Patients must have had no seizures in the last 6 months.
  • Patients must not have uncontrolled intercurrent illness including uncontrolled hypertension, symptomatic congestive heart failure, unstable angina, uncontrolled cardiac arrhythmia, uncontrolled psychiatric illness or social situation that would limit compliance with the study, or a prior history of Stevens Johnson Syndrome.
  • ECOG performance status 0, 1, or 2. (PS 3 allowed if secondary to pain)
  • Patients with monoclonal gammopathy of undetermined significance or asymptomatic multiple myeloma are not eligible.
  • Patients must not have Grade 2 or higher peripheral neuropathy by CTCAE 4.0.
  • Patients must not have active, uncontrolled infection.
  • Patients may have a history of current or previous deep vein thrombosis or pulmonary embolism but must be willing to take some form of anti-coagulation as prophylaxis if they are not currently on full-dose anticoagulation.
  • Patients should not have New York Heart Association classification III or IV heart failure or myocardial infarction within the previous 6 months.
  • Patients with a history of prior malignancy are eligible provided they were treated with curative intent and do not require active therapy (currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma “in situ” of the cervix or breast are not excluded).
  • 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 starting 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. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. See Appendix V: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods.
  • Sexually active males must be willing to use a condom (even if they have undergone a prior vasectomy) while having intercourse, while taking lenalidomide and for 4 weeks after stopping treatment.
  • The following patients will be excluded as this study involves an agent that may have genotoxic, mutagenic and teratogenic effects.
  • Pregnant women
  • Nursing women
  • HIV infection is not excluded. Known HIV positive patients must meet the following criteria:
    • CD4 cell count ≥ 350/mm3
    • No history of AIDS-related illness
    • Not currently prescribed zidovudine or stavudine
  • Patient enrolling to this study must agree to register to the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.

Step 2 Randomization

  • Patients must not have experienced progression on Step 1 induction therapy.
  • Step 2 registration must be within 28 days of completing Step 1 therapy.
  • Patients must not have received any non-protocol therapy outside of the assigned induction therapy.
  • ECOG performance status 0, 1, or 2. (PS 3 allowed if secondary to pain).
  • Any adverse event related to Step 1 therapy must have resolved to grade 2 or less.
  • Patient must have adequate laboratory levels as follows (within 28 days prior to randomization to Step 2)
    • Hemoglobin ≥ 8 g/dL.
    • Platelet count ≥ 75,000 cells/mm3.
    • Absolute neutrophil count ≥ 1000 cells/mm3.
    • Calculated creatinine clearance ≥ 30 mL/min.
    • Bilirubin ≤ 1.5 mg/dL.
    • SGPT (ALT) and SGOT (AST) < 2.5 times the upper limit of normal.
  • 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 starting 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.
  • Sexually active males must be willing to use a condom (even if they have undergone a prior vasectomy) while having intercourse, while taking lenalidomide and for 4 weeks after stopping treatment.
  • The following patients will be excluded as this study involves an agent that may have genotoxic, mutagenic and teratogenic effects.
    • Pregnant women
    • Nursing women
  • Patient enrolling to this study must agree to register to the mandatory RevAssist® program and be willing and able to comply with the requirements of RevAssist®.





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