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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified February 2017 by University of Arkansas
Sponsor:
Collaborator:
Janssen, LP
Information provided by (Responsible Party):
University of Arkansas
ClinicalTrials.gov Identifier:
NCT03004287
First received: December 19, 2016
Last updated: February 23, 2017
Last verified: February 2017
  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

Condition Intervention Phase
Multiple Myeloma
Drug: Carfilzomib
Drug: Thalidomide
Drug: Dexamethasone
Drug: Daratumumab
Drug: Cisplatin
Drug: Adriamycin
Drug: Cyclophosphamide
Drug: Etoposide
Drug: Melphalan
Procedure: ASCT
Drug: Lenalidomide
Drug: Bortezomib
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of Arkansas:

Primary Outcome Measures:
  • Measure the progression-free survival in patients with high risk multiple myeloma [ Time Frame: 48 months ]

Estimated Enrollment: 50
Anticipated Study Start Date: May 1, 2017
Estimated Study Completion Date: January 2021
Estimated Primary Completion Date: January 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Study Treatment

Induction 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.

Drug: Carfilzomib
Given by vein: days 1 and 2 of Induction; days 1, 8, 15, and 22 of Consolidation 1; and days 1, 8, 15, and 22 of alternating 3-month blocks during Maintenance.
Other Name: Kyprolis
Drug: Thalidomide
Given by mouth at bedtime: days 1-4 of Induction
Other Name: Thalomid
Drug: Dexamethasone
Given by mouth or by vein: days 1-4 of Induction; days -4 - -1 of Transplant(s); and days 1, 8, 15, and 22 of every cycle during Maintenance
Other Name: Baycadron
Drug: Daratumumab
Given by vein: day -1 of induction; days 1 and 8 of Immunological Consolidations; and day 1 of each Maintenance cycle
Other Name: Darzalex
Drug: Cisplatin
Given by vein: days 1-4 (continuous infusion) of Induction
Other Name: Platinol
Drug: Adriamycin
Given by vein: days 1-4 (continuous infusion) of Induction
Other Name: Doxorubicin
Drug: Cyclophosphamide
Given by vein: days 1-4 (continuous infusion) of Induction
Other Name: Cytoxan
Drug: Etoposide
Given by vein: days 1-4 (continuous infusion) of Induction
Other Name: Eposin
Drug: Melphalan
Given by vein: days -4 - -1 of Transplant(s)
Procedure: ASCT
day 0 of Transplant(s)
Drug: Lenalidomide
Given by mouth: days 1-21 of alternating 3-month blocks during Maintenance
Other Name: Revlimid
Drug: Bortezomib
Given by vein or subcutaneous injection: may be substituted for carfilzomib throughout the study regimen at the discretion of the treating physician
Other Name: Velcade

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.
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03004287

Contacts
Contact: Nathan M Petty 501-526-6990 ext 2435 pettynathanm@uams.edu
Contact: David A Avery 501-526-6990 ext 2431 daavery@uams.edu

Sponsors and Collaborators
University of Arkansas
Janssen, LP
Investigators
Principal Investigator: Faith E Davies University of Arkansas for Medical Science-Myeloma Institute
  More Information

Responsible Party: University of Arkansas
ClinicalTrials.gov Identifier: NCT03004287     History of Changes
Other Study ID Numbers: 206241
Study First Received: December 19, 2016
Last Updated: February 23, 2017
Individual Participant Data  
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Etoposide phosphate
Lenalidomide
Daratumumab
Liposomal doxorubicin
Cisplatin
Dexamethasone
Cyclophosphamide
Bortezomib
Etoposide
Thalidomide
Doxorubicin
Melphalan
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Antineoplastic Agents

ClinicalTrials.gov processed this record on March 22, 2017