Clinical Trials /

2015-12: A Study Exploring the Use of Early and Late Consolidation/Maintenance Therapy

NCT03004287

Description:

This study will assess whether adding one of the newest multiple myeloma therapies, daratumumab, into the Total Therapy approach helps patients live longer with fewer side effects

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 2015-12: A Study Exploring the Use of Early and Late Consolidation/Maintenance Therapy
  • Official Title: 2015-12: A Phase II Study Exploring the Use of Early and Late Consolidation/Maintenance With Anti-CD38 (Protein) Monoclonal Antibody to Improve Progression Free Survival in Patients With Newly Diagnosed Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: 206241
  • NCT ID: NCT03004287

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
CarfilzomibKyprolisStudy Treatment
ThalidomideThalomidStudy Treatment
DexamethasoneBaycadronStudy Treatment
DaratumumabDarzalexStudy Treatment
CisplatinPlatinolStudy Treatment
AdriamycinDoxorubicinStudy Treatment
CyclophosphamideCytoxanStudy Treatment
EtoposideEposinStudy Treatment
MelphalanStudy Treatment
LenalidomideRevlimidStudy Treatment
BortezomibVelcadeStudy Treatment

Purpose

This study will assess whether adding one of the newest multiple myeloma therapies, daratumumab, into the Total Therapy approach helps patients live longer with fewer side effects

Detailed Description

      Past studies conducted at the Myeloma Institute and at other institutions have shown that
      many patients with high-risk disease (as determined by gene array studies - studies that look
      at specific genes using special equipment) tend to have shorter remissions (disappearance of
      signs and symptoms of myeloma) and do not survive as long as participants with low-risk
      myeloma. The Total Therapy approach to treatment carried out at the Myeloma Institute where
      multiple chemotherapy agents are given as induction followed by a stem cell transplant,
      post-transplant consolidation, and maintenance therapy has proven to be the best available
      treatment strategy. However, the availability of new treatments that work in different ways
      offers the possibility of improving the effectiveness of Total Therapy treatment while
      potentially reducing the number of side effects patients' experience. Daratumumab is a human
      monoclonal antibody or protein drug. It recognizes a specific protein, CD38, which is found
      at high levels on multiple myeloma cells. An antibody is something that finds and kills
      foreign objects in your body, in this case, myeloma cells. The other drugs that will be used
      in the study treatment regimen include carfilzomib or bortezomib, thalidomide, lenalidomide,
      dexamethasone, cisplatin, adriamycin, cyclophosphamide, etoposide, lenalidomide and
      dexamethasone.
    

Trial Arms

NameTypeDescriptionInterventions
Study TreatmentExperimentalInduction Chemotherapy: Carfilzomib, Thalidomide, Dexamethasone, Daratumumab , CisPlatin, Adriamycin, Cyclophosphamide and Etoposide (KTD-Dara-PACE). Autologous Stem Cell Transplant (ASCT) 1: Melphalan, Dexamethasone, ASCT. Immunological Consolidation 1: Daratumumab. Consolidation 1: Daratumumab, Carfilzomib, Dexamethasone (Dara-KD). ASCT 2 (optional): Melphalan, Dexamethasone, ASCT. Immunological Consolidation 2: Daratumumab. Maintenance: Dara-KD alternating with Daratumumab, lenalidomide, and Dexamethasone (Dara-RD) in 3-month blocks. Bortezomib may be substituted for carfilzomib throughout the regimen at the discretion of the treating physician.
  • Carfilzomib
  • Thalidomide
  • Dexamethasone
  • Daratumumab
  • Cisplatin
  • Adriamycin
  • Cyclophosphamide
  • Etoposide
  • Melphalan
  • Lenalidomide
  • Bortezomib

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have newly diagnosed active Multiple Myeloma (MM) requiring treatment.
             Patients with a previous history of smoldering myeloma will be eligible if there is
             evidence of progressive disease requiring chemotherapy.

          -  Patients must be either untreated or have not received more than four cycles of
             systemic MM therapy (e.g. Revlimid Dexamethasone (RD), Bortezomib Revlimid
             Dexamethasone (VRD). Prior bisphosphonates and localized radiation are allowed.

          -  Participants must have high-risk disease, as defined by at least one of the following:

          -  Myeloma Prognostic Risk Signature (MyPRS) risk score ≥ 50.4

          -  Lactate Dehydrogenase (LDH) ≥ 360 U/L (Rule out hemolysis and infection; contact PI if
             any doubt.)

          -  Diagnosis of primary plasma cell leukemia.

          -  Eastern Cooperative Oncology Group (ECOG) ≤ 2, unless solely due to symptoms of
             MM-related bone disease.

          -  Patients must have a platelet count ≥ 50,000/μL, unless lower levels are explained by
             extensive bone marrow plasmacytosis.

          -  Patients must be at least 18 years of age and not older than 75 years of age at the
             time of registration.

          -  Participants must have a baseline serum creatinine level < 3 mg/dL and baseline
             Alanine Aminotransferase (ALT) < 3x Upper Limit of Normal (ULN).

          -  Participants must have an ejection fraction by echocardiogram (ECHO) or Multiple-gated
             Acquisition Scan (MUGA) scan ≥ 45%

          -  Patients must have adequate pulmonary function studies > 50% of predicted on
             mechanical aspects (Forced Expiratory Volume 1 (FEV1), Forced Vital Capacity (FVC) and
             diffusion capacity (DLCO) > 50% of predicted. If the patient is unable to complete
             pulmonary function tests due to MM related pain or other conditions, an exception may
             be granted if the principal investigator documents that the patient is a candidate for
             high dose therapy.

          -  Patients must have signed an Institutional Review Board (IRB)-approved informed
             consent indicating their understanding of the proposed treatment and that the protocol
             has been approved by the Institutional Review Board (IRB).

        Exclusion Criteria:

          -  No evidence of high-risk disease

          -  Poorly controlled hypertension, diabetes mellitus, active or uncontrolled hepatitis,
             or other serious medical or psychiatric illness that could potentially interfere with
             the completion of treatment according to this protocol.

          -  Patients must not have prior malignancy, except for adequately treated basal cell or
             squamous cell skin cancer, in situ cervical cancer, or other cancer for which the
             patient has not received treatment for one year prior to enrollment. Other cancers
             will only be acceptable if the patient's life expectancy exceeds five years.

          -  Pregnant or nursing women may not participate. Women of childbearing potential must
             have a negative pregnancy documented within one week of registration.

          -  Subjects of reproductive potential may not participate unless they have agreed to use
             an effective contraceptive method.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Measure the progression-free survival in patients with high risk multiple myeloma
Time Frame:48 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Arkansas

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