Clinical Trials /

Carfilzomib Based Chemotherapy Mobilization for Autologous Stem Cell Transplants in Multiple Myeloma

NCT03909412

Description:

This phase I study utilizes a 3+3 design with escalating cohorts of Carfilzomib at 20mg/m2, 27mg/m2, 36mg/m2, 45mg/m2, 56mg/m2, and 70mg/m2 to be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone and G-CSF

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Carfilzomib Based Chemotherapy Mobilization for Autologous Stem Cell Transplants in Multiple Myeloma
  • Official Title: Phase I Study of Carfilzomib-based Chemotherapy Mobilization for Autologous Stem Cell Transplantation in Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: Pro2018-0531
  • NCT ID: NCT03909412

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
CarfilzomibKyprolisCarfilzomib Mobilization - Dose Level 0
CyclophosphamideCytoxanCarfilzomib Mobilization - Dose Level 0
DexamethasoneDecadronCarfilzomib Mobilization - Dose Level 0
Granulocyte Colony-Stimulating FactorG-CSF, Filgrastim, NeupogenCarfilzomib Mobilization - Dose Level 0

Purpose

This phase I study utilizes a 3+3 design with escalating cohorts of Carfilzomib at 20mg/m2, 27mg/m2, 36mg/m2, 45mg/m2, 56mg/m2, and 70mg/m2 to be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone and G-CSF

Detailed Description

      This study will be conducted as an open-label Phase I, single-center study in which subjects
      will receive carfilzomib, in combination cyclophosphamide and dexamethasone, for mobilization
      of peripheral blood stem cells. Study treatment will be administered in sequential cohorts,
      with three to six subjects in each cohort.

      Following induction therapy, eligible patients will complete screening procedures. Treatment
      will consist of Dexamethasone 40mg IV/PO to be administered as a premedication. Carfilzomib
      dosed at each respective cohort level to be administered over 30 minutes followed by
      Cyclophosphamide dosed at 2gm/m2 administered over 1 hour.

      For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib
      (20mg/m2) will be administered 1 week prior to the cohort dosing.

      On day 7 subjects will initiate high dose G-CSF injections at 14mcg/kg daily (with a cap of
      1440mcg daily). On day 12 peripheral blood stem cell collection will begin per institutional
      protocol.

      After successful peripheral blood stem cell mobilization, patients will proceed to a
      melphalan based autologous stem cell transplant.

      Patients will have disease parameters assessed monthly after the transplant.
    

Trial Arms

NameTypeDescriptionInterventions
Carfilzomib Mobilization - Dose Level 0ExperimentalCarfilzomib at 20mg/m2 over 10 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF. For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
  • Carfilzomib
  • Cyclophosphamide
  • Dexamethasone
  • Granulocyte Colony-Stimulating Factor
Carfilzomib Mobilization - Dose Level 1ExperimentalCarfilzomib at 27mg/m2 over 10 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF. For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
  • Carfilzomib
  • Cyclophosphamide
  • Dexamethasone
  • Granulocyte Colony-Stimulating Factor
Carfilzomib Mobilization - Dose Level 2ExperimentalCarfilzomib at 36mg/m2 over 30 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF. For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
  • Carfilzomib
  • Cyclophosphamide
  • Dexamethasone
  • Granulocyte Colony-Stimulating Factor
Carfilzomib Mobilization - Dose Level 3ExperimentalCarfilzomib at 45mg/m2 over 30 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF. For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
  • Carfilzomib
  • Cyclophosphamide
  • Dexamethasone
  • Granulocyte Colony-Stimulating Factor
Carfilzomib Mobilization - Dose Level 4ExperimentalCarfilzomib at 56mg/m2 over 30 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF. For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
  • Carfilzomib
  • Cyclophosphamide
  • Dexamethasone
  • Granulocyte Colony-Stimulating Factor
Carfilzomib Mobilization - Dose Level 5ExperimentalCarfilzomib at 70mg/m2 over 30 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF. For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
  • Carfilzomib
  • Cyclophosphamide
  • Dexamethasone
  • Granulocyte Colony-Stimulating Factor

Eligibility Criteria

        INCLUSION CRITERIA

          -  Subject has voluntarily agreed to participate by giving written informed consent
             before performance of any study-related procedure not part of normal medical care,
             with the understanding that consent may be withdrawn by the subject at any time
             without prejudice to future medical care. Informed Consent must be obtained prior to
             mobilization.

          -  Subject has a confirmed diagnosis of multiple myeloma as specified by the
             International Myeloma Working Group criteria and must have measurable disease as
             defined by at least one of the following criteria:

          -  Serum monoclonal protein ≥ 0.5 g/dL

          -  ≥200 mg of monoclonal protein in the urine on 24-hour electrophoresis

          -  Serum immunoglobulin free light chain: involved FLC ≥ 10 mg/dL (≥ 100 mg/L) AND
             abnormal serum immunoglobulin kappa to lambda free light chain ratio

          -  Subject is ≥18 years of age at the time of signing the informed consent form.

          -  Subject has an ECOG performance status of < 2.

          -  Subjects must have measurable monoclonal protein, free light chains, and/or M-spike in
             blood or urine.

          -  Subjects must have completed any "induction therapy"and have achieved less than a CR.

          -  Subject has a life expectancy of >12 weeks.

               -  Absolute neutrophil count (ANC) ≥1000 cells/mm3 (≥500 for patients with bone
                  marrow biopsy displaying >50% involvement by myeloma)

               -  Platelets count ≥ 50,000/mm3 (≥ 30,000 for patients with bone marrow biopsy
                  displaying >50% involvement by myeloma)

               -  Hemoglobin > 9.0 g/dL

               -  Serum SGOT/AST <3.0 x upper limits of normal (ULN)

               -  Serum SGPT/ALT <3.0 x upper limits of normal (ULN)

               -  Serum total bilirubin <1.5 x ULN

          -  Subject must have a MUGA scan or echo with LVEF >50% within 6 months of enrollment.

          -  Females of childbearing potential (FCBP) must have a negative serum pregnancy test
             should be done within 7 days of treatment initiation and a negative urine pregnancy
             test within the 24 hours prior to the first study drug administration

          -  FCBP and male subjects who are sexually active with FCBP must agree to use 2 highly
             effective concomitant methods of contraception including a male condom during the
             study and for 90 days following the last dose of study treatment

          -  Male subjects must agree to not donate sperm while taking carfilzomib and for 90 days
             after the last dose of carfilzomib.

        EXCLUSION CRITERIA

          -  Subject has a history of allergic reactions to compounds containing captisol, or
             Carfilzomib

          -  Subject has a NYHA Class III or IV heart disease and/or a history of active unstable
             angina, congestive heart disease, severe uncontrolled cardiac arrhythmia,
             electrocardiographic evidence of acute ischemia, active conduction system
             abnormalities or myocardial infarction within 6 months prior to enrollment. Prior to
             study entry, any ECG abnormality at Screening has to be documented by the investigator
             as not medically relevant.

          -  Uncontrolled hypertension

          -  Pulmonary hypertension

          -  Subject has a known HIV or hepatitis A, B, or C positivity---ONLY IF ACTIVE

          -  Subject has active viral or bacterial infections or any coexisting medical problem
             that would significantly increase the risks of this treatment program.

          -  Subject has concurrent, uncontrolled medical condition, laboratory abnormality, or
             psychiatric illness which could place him/her at unacceptable risk, including, but not
             limited to, uncontrolled hypertension, uncontrolled diabetes, active uncontrolled
             infection, and/or acute chronic liver disease (i.e., hepatitis, cirrhosis).

          -  Subject has ≥Grade 2 peripheral neuropathy.

          -  Subject has been diagnosed or treated for another malignancy within 3 years of
             enrollment, with the exception of complete resection of basal cell carcinoma or
             squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate
             cancer after curative therapy.

          -  Subject has received radiation therapy within 3 weeks of enrollment Enrollment of
             subjects who require concurrent radiotherapy (which must be localized in its field
             size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed
             since the last date of therapy.

          -  Subject has had prior mobilization or stem cell transplant.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame:24 Months
Safety Issue:
Description:Safety and tolerability will be assessed by clinical review of all relevant parameters including Adverse Events (CTCAE v4.0)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hackensack Meridian Health

Last Updated

October 17, 2019