Clinical Trials /

Carfilzomib, Pomalidomide, and Dexamethasone in Treating Patients With High-Risk Multiple Myeloma

NCT03756896

Description:

This phase II trial studies how well carfilzomib, pomalidomide, and dexamethasone work in treating patients with high-risk multiple myeloma. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as pomalidomide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving carfilzomib, pomalidomide, and dexamethasone may work better in treating patients with multiple myeloma.

Related Conditions:
  • Multiple Myeloma
  • Plasma Cell Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Carfilzomib, Pomalidomide, and Dexamethasone in Treating Patients With High-Risk Multiple Myeloma
  • Official Title: Consolidation and Maintenance Therapy With Carfilzomib, Pomalidomide and Dexamethasone (CPD) in High-Risk Myeloma Patients: A Phase 2 Study With a Safety Run-In

Clinical Trial IDs

  • ORG STUDY ID: IRB00097882
  • SECONDARY ID: NCI-2017-02052
  • SECONDARY ID: Winship4101-17
  • NCT ID: NCT03756896

Conditions

  • Plasma Cell Myeloma

Interventions

DrugSynonymsArms
CarfilzomibKyprolis, PR-171Carfilzomib, pomalidomide, dexamethasone
DexamethasoneDecadron, Dekacort, Dexameth, HexadrolCarfilzomib, pomalidomide, dexamethasone
Pomalidomide4-Aminothalidomide, Actimid, CC-4047, Imnovid, PomalystCarfilzomib, pomalidomide, dexamethasone

Purpose

This phase II trial studies how well carfilzomib, pomalidomide, and dexamethasone work in treating patients with high-risk multiple myeloma. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as pomalidomide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving carfilzomib, pomalidomide, and dexamethasone may work better in treating patients with multiple myeloma.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To determine the ≥ complete response (CR) rates with carfilzomib, pomalidomide and
      dexamethasone (CPD) consolidation and maintenance.

      SECONDARY OBJECTIVES:

      I. To determine the improved progression free survival (PFS) with CPD consolidation and
      maintenance among high-risk patients.

      II. To determine the best response rates (very good partial response rate [VGPR], stringent
      complete response [sCR] rate) with CPD consolidation and maintenance.

      II. To evaluate the safety of the CPD combination as consolidative and maintenance regimen.

      III. To characterize safety in subjects who receive CPD consolidation and maintenance.

      IV. To evaluate the duration of response (DOR).

      V. To evaluate the overall survival (OS) in high-risk patients.

      VI. To evaluate the minimal residual disease (MRD) detection with CPD consolidation and
      maintenance.

      OUTLINE:

      CONSOLIDATION: Patients receive carfilzomib intravenously (IV) over 30 minutes on days 1, 2,
      8, 9, 15, and 16, pomalidomide orally (PO) daily on days 1-21, and dexamethasone PO daily on
      days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 2 courses in the
      absence of disease progression or unacceptable toxicity.

      MAINTENANCE: Patients receive carfilzomib IV over 30 minutes on days 1, 8, and 15,
      pomalidomide PO daily on days 1-21, and dexamethasone PO daily on days 1, 8, and 15. Courses
      repeat every 28 days in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months.
    

Trial Arms

NameTypeDescriptionInterventions
Carfilzomib, pomalidomide, dexamethasoneExperimentalCONSOLIDATION: Patients receive carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16, pomalidomide PO daily on days 1-21, and dexamethasone PO daily on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive carfilzomib IV over 30 minutes on days 1, 8, and 15, pomalidomide PO daily on days 1-21, and dexamethasone PO daily on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Carfilzomib
  • Dexamethasone
  • Pomalidomide

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must meet the following criteria on screening examination to be eligible to
             participate in the study; all laboratory assessments should be performed within 21
             days of initiation of protocol therapy unless otherwise specified; subject is, in the
             investigator's opinion, willing and able to comply with the protocol requirements

          -  Subject has given voluntary signed written informed consent before performance of any
             study-related procedure that is not part of normal medical care, with the
             understanding that consent may be withdrawn by the subject at any time without
             prejudice to their future medical care

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1

          -  Subject is a transplant-eligible patient that have undergone autologous stem cell
             transplant (ASCT) within one year of their diagnosis and have achieved ≥ partial
             response (PR) based on International Myeloma Working Group (IMWG) standard criteria

          -  Patients with high risk disease defined as

               -  Presence of del(17p); t(4;14); t(14;16); by fluorescence in situ hybridization
                  (FISH) or by cytogenetics (CTG)

               -  Plasma cell leukemia at diagnosis with ≥ 20% circulating plasma cells on
                  peripheral blood

          -  Subject agrees to refrain from blood donations during therapy on study and for 90 days
             after therapy is completed

          -  Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
             test with a sensitivity of at least 50 milli-International units (mIU)/mL within 10-14
             days prior to and again within 24 hours of starting pomalidomide 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 pomalidomide
             through 90 days after the last dose of study drug; 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 vasectomy from the time of signing the informed consent
             form through 90 days after the last dose of study drug; all patients must be
             registered in and must comply with all requirements of the pomalidomide Risk
             Evaluation and Mitigation Strategies (REMS) program; male subjects should refrain from
             sperm donation for at least 90 days after the last dose of carfilzomib or pomalidomide

               -  FCBP refers to sexually mature female, regardless of sexual orientation or
                  whether they have undergone tubal ligation, who: 1) has not undergone a
                  hysterectomy or bilateral oophorectomy; or 2) has not been naturally menopausal
                  for at least 24 consecutive months

        Exclusion Criteria:

          -  Diagnosed with smoldering multiple myeloma (MM), monoclonal gammopathy of undetermined
             significance, Waldenstrom's macroglobulinemia, polyneuropathy, organomegaly,
             endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, amyloidosis
             or standard risk myeloma or secondary plasma cell leukemia

          -  High risk patients that did not achieve ≥ PR after stem cell transplant

          -  Participant has ≥ grade 2 peripheral neuropathy on clinical examination within 21 days
             before initiation of protocol therapy

          -  Creatinine clearance < 30 mL/min (either actual or calculated value), within 21 days
             of initiation of protocol therapy; the Cockcroft-Gault formula should be used for
             calculating creatinine clearance values

          -  Platelet count < 75,000 cells/mm³ at time of screening evaluation; transfusion may not
             be used to meet platelet eligibility criteria within 7 days of obtaining screening
             evaluation

          -  Participants with an absolute neutrophil count (ANC) < 1000 cells/mm³ at time of
             screening evaluation; growth factors may not be used to meet ANC eligibility criteria
             within 14 days of obtaining screening evaluation

          -  Participants with hemoglobin level < 8.0 g/dL, at time of screening; transfusion may
             not be used to meet eligibility criteria within 7 days of obtaining screening
             evaluation

          -  Bilirubin > 1.5 x institutional upper limit of normal (ULN), within 21 days of
             initiation of protocol therapy

          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]),
             alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]), or
             alkaline phosphatase > 3 x institutional ULN, within 21 days of initiation of protocol
             therapy

          -  Other ongoing or prior anti-myeloma therapy; patients may be receiving concomitant
             therapy with bisphosphonates and low dose corticosteroids (e.g., prednisone up to but
             no more than 10 mg p.o. once daily [q.d.] or its equivalent) for symptom management
             and comorbid conditions; doses of corticosteroid should be stable for at least 7 days
             prior to study treatment)

          -  Known significant cardiac abnormalities including:

               -  Congestive heart failure, New York Heart Association (NYHA) class III or IV

               -  Uncontrolled angina, arrhythmia or hypertension

               -  Myocardial infarction within the past six months

               -  Any other uncontrolled or severe cardiovascular condition

               -  Prior cerebrovascular event with residual neurologic deficit

          -  Serious, intercurrent illness including, but not limited to, clinically relevant
             active infection, known active hepatitis B or C viral infection, known human
             immunodeficiency virus (HIV) infection, uncontrolled diabetes mellitus, or serious
             co-morbid medical conditions such as chronic restrictive pulmonary disease, and
             cirrhosis

          -  Any condition, including laboratory abnormalities, that in the opinion of the
             investigator places the subject at unacceptable risk if he/she were to participate in
             the study

          -  Prior malignancy (within the last 5 years) except for adequately treated basal cell or
             squamous cell skin cancer, or in situ cervical cancer

          -  Known hypersensitivity to acyclovir or similar anti-viral drug

          -  Known intolerance to steroid therapy

          -  Contraindication or prior intolerance to thromboembolic prophylaxis with aspirin,
             warfarin or low-molecular weight heparin

          -  Participants with known central nervous system (CNS) disease

          -  Poor tolerability or known allergy to any of the study drugs or compounds of similar
             chemical or biologic composition to dexamethasone, boron or mannitol

          -  Female participants pregnant or breast-feeding

          -  Participants who have undergone major surgery ≤ 4 weeks prior to starting study drug
             or who have not recovered from side effects of the surgery

          -  Participants with any significant history of non-compliance to medical regimens or
             unwilling or unable to comply with the instructions given to him/her by the study
             staff
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:≥ Complete response (CR) rates
Time Frame:Up to 2 years after study start
Safety Issue:
Description:Completed response (CR) rates will be determined for CPD consolidation and maintenance.

Secondary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:From first dose until documented progression or death, assessed at 18 months
Safety Issue:
Description:Progression-free survival (PFS) is defined as the time from first dose until documented progression or death. A subject who neither progresses nor dies will be censored on the date of his or her last tumor assessments. PFS will be determined by using all enrolled patients in accordance with the intention to treat (ITT) principle.
Measure:Best response on-study
Time Frame:Up to 2 years after study start
Safety Issue:
Description:Best response on-study refers to the best response (very good partial response rate [VGPR], stringent complete response [sCR] rate) prior to discontinuation of all study therapy.
Measure:Objective response rate (ORR) defined as the proportion of treated subjects who achieve a best response of CR, stringent complete response (sCR), very good partial response (VGPR), or partial response (PR)
Time Frame:Up to 2 years after study start
Safety Issue:
Description:The objective response rate (ORR) will be assessed using International Myeloma Working Group (IMWG) criteria.
Measure:Duration of response (DOR)
Time Frame:From first response (PR or better) until a progression event (documented progression or death), assessed up to 2 years
Safety Issue:
Description:Duration of response (DOR) is the time from first response (PR or better) until a progression event (documented progression or death). Only subjects who ever achieved a response of PR or better will be considered. Subjects who neither progress nor die will be censored on the date of their last tumor assessment.
Measure:Overall survival (OS)
Time Frame:Up to 2 years after study start
Safety Issue:
Description:Overall survival (OS) is defined as the time from first dose until documented death.
Measure:Minimal residual disease (MRD) detection
Time Frame:Up to 2 years after study start
Safety Issue:
Description:The achievement of minimal residual disease (MRD) will be evaluated and reported on patients that achieve a complete response. MRD testing will be performed by adaptive clonoSEQ testing.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Emory University

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