Clinical Trials /

A Study of Carfilzomib, Lenalidomide, Dexamethasone and Daratumumab for Patients With Relapsed/Refractory Myeloma With Salvage Autologous Hematopoietic Cell Transplantation

NCT03556332

Description:

The purpose of this study is to test any good and bad effects of giving a combination of study drugs before and after autologous stem cell transplant.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Carfilzomib, Lenalidomide, Dexamethasone and Daratumumab for Patients With Relapsed/Refractory Myeloma With Salvage Autologous Hematopoietic Cell Transplantation
  • Official Title: Phase 2 Trial of Intensive Chemo-immunotherapy With Carfilzomib, Lenalidomide, Dexamethasone and Daratumumab for Relapsed/Refractory Myeloma in the Context of Salvage Autologous Hematopoietic Cell Transplantation

Clinical Trial IDs

  • ORG STUDY ID: 17-493
  • NCT ID: NCT03556332

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
CarfilzomibCarfilzomib, Lenalidomide, Dexamethasone and Daratumumab & HCT
LenalidomideCarfilzomib, Lenalidomide, Dexamethasone and Daratumumab & HCT
DexamethasoneCarfilzomib, Lenalidomide, Dexamethasone and Daratumumab & HCT
DaratumumabCarfilzomib, Lenalidomide, Dexamethasone and Daratumumab & HCT

Purpose

The purpose of this study is to test any good and bad effects of giving a combination of study drugs before and after autologous stem cell transplant.

Trial Arms

NameTypeDescriptionInterventions
Carfilzomib, Lenalidomide, Dexamethasone and Daratumumab & HCTExperimentalAfter receiving four 28-day cycles of Dara-CRd, eligible patients will then undergo HCT with high dose melphalan conditioning. Sixty to ninety days after HCT, patients will receive another 4 cycles of Dara-CRd.
  • Carfilzomib
  • Lenalidomide
  • Dexamethasone
  • Daratumumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patient must be capable, willing, and able to provide written, informed consent.

          -  Age ≥ 18-years-old and <= 75-years-old.

          -  Histologic confirmation of multiple myeloma by the enrolling institution

          -  Symptomatic myeloma that has progressed/relapsed after 1 to 3 prior lines of therapy

          -  Patients who have received <=1 cycle of therapy after most recent progression/relapse
             are eligible to enroll on study

               -  Treatment of hypercalcemia or spinal cord compression or aggressively progressing
                  myeloma with current or prior corticosteroids is permitted

               -  Bisphosphonates are permitted

               -  Concurrent or prior treatment with corticosteroids for indications other than
                  multiple myeloma is permitted

               -  Prior treatment with radiotherapy is permitted

               -  Patients with measurable disease who received up to one cycle of any therapy
                  within 60 days with a washout period of 4 weeks from last dose (on a trial or
                  outside a trial) are eligible

               -  Maintenance single agent imid (ie. lenalidomide or pomalidomide) or monoclonal
                  antibody (ie. daratumumab) do not require the 4-week washout period

          -  More than 2 x 10^6 autologous CD34+ cells/kg cryopreserved. The graft may not be CD34+
             selected or otherwise manipulated to remove tumor or other cells. The graft can be
             collected at the transplanting institution or by a referring center.

          -  Planning to receive autologous HCT per institutional standards as part of standard of
             care. Eligibility for autologous HCT should be based on institutional guidelines.

          -  However, at minimum all patients must meet the following criteria:

               -  KPS greater than 70

               -  Cardiac left ventricular ejection fraction of greater than 40%

               -  Calculated creatinine clearance of greater than 40 cc/min

               -  AST and ALT of less than 2 x upper limit of normal

               -  Direct bilirubin of less than 2 x upper limit of normal

               -  Total bilirubin of less than 2 x upper limit of normal. If Total bilirubin is
                  abnormal. Direct bilirubin of less than 2 x upper limit of normal

          -  Measurable disease as defined by any of the following International Myeloma Working
             Group Criteria

               -  Monoclonal serum peak of greater than 0.5 gms per deciliter

               -  Measurable urine peak as defined by urine protein electrophoresis of greater than
                  100 mg per 24 hours

               -  Serum FLC assay: involved FLC level ≥10 mg/dL provided serum FLC ratio is
                  abnormal

          -  Hemoglobin ≥ 8 g/dL (80 g/L) within 14 days prior to enrollment (subjects may be
             receiving red blood cell [RBC] transfusions in accordance with institutional
             guidelines)

          -  Platelet count ≥ 50 × 109/L (≥ 30 × 109/L if myeloma involvement in the bone marrow is
             > 50%) within 14 days prior to initial treatment (subjects may be receiving platelet
             transfusions in accordance with institutional guidelines) .

          -  Women of childbearing potential (WOCBP) † must agree to ongoing pregnancy testing and
             to practice contraception as described in section 9.3 and required by the Revlimid
             REMS program.

             † A woman of childbearing potential is a sexually mature female who has not undergone
             a hysterectomy or bilateral oophorectomy or has not been naturally postmenopausal for
             at least 24 consecutive months (i.e. has had menses at any time in the preceding 24
             consecutive months).

          -  Male subjects must agree to practice contraception

          -  All study participants must be registered into the mandatory Revlimid REMS program and
             be willing and able to comply with the requirements of the REMS program.

        Exclusion Criteria:

          -  Plasma cell leukemia (>20% circulating plasma cells) during screening studies

          -  POEMS syndrome

          -  Pregnant or lactating females. Because there is a potential risk for adverse events
             nursing infants secondary to treatment of the mother with carfilzomib in combination
             with lenalidomide. These potential risks may also apply to other agents used in this
             study.

          -  Uncontrolled hypertension or diabetes

          -  Active hepatitis B or C infection

               -  Patients with HBV core antibody positive, but HBV PCR negative are eligible if
                  they are on medication for suppression of HBV reactivation

               -  Patients with HCV antibody positive, but PCR negative are eligible.

          -  Serologically positive HIV (testing required during screening)

          -  Significant cardiovascular disease with NYHA Class III or IV symptoms, EF<40% or
             hypertrophic cardiomyopathy, or restrictive cardiomyopathy, or myocardial infarction
             within 6 months prior to enrollment, or unstable angina, or unstable arrhythmia as
             determined by history and physical examination. Echocardiogram will be performed
             during screening evaluation.

          -  Moderate or severe pulmonary hypertension defined as PASP >50 mm Hg

          -  Refractory GI disease that would prevent absorption of oral agents

          -  Uncontrolled intercurrent illness including but not limited to active infection or
             psychiatric illness/social situations that would compromise compliance with study
             requirements

          -  Significant neuropathy ≥Grade 3 or Grade 2 neuropathy with pain at baseline

          -  Contraindication to any concomitant medication, including antivirals or
             anticoagulation.

          -  Major surgery within 3 weeks prior to first dose

          -  Prior Allogeneic HCT (prior autologous transplant is allowed regardless of response)

          -  History of CNS involvement by myeloma

          -  Disease progression as defined by IMW Criteria1 on the combination of carfilzomib,
             lenalidomide and dexamethasone (Patients with progression on lenalidomide maintenance
             after completion of carfilzomib, lenalidomide and dexamethasone combination therapy
             will be eligible).

          -  Disease progression on daratumumab

          -  Prior dose limiting toxicity from carfilzomib or lenalidomide.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:number of patients with complete remission (CR) rate
Time Frame:3 years
Safety Issue:
Description:Traditional Response Criteria from International Myeloma Working Group Criteria for Multiple Myeloma

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Carfilzomib
  • Lenalidomide
  • Dexamethasone
  • Daratumumab
  • salvage autologous hematopoietic cell transplantation
  • 17-493

Last Updated

October 17, 2019