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

NCT03004287 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 206241
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Measure the progression-free survival in patients with high risk multiple myeloma

  48 months

Study Arms (1)

Study Treatment

EXPERIMENTAL

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; Drug: Thalidomide; Drug: Dexamethasone; Drug: Daratumumab; Drug: Cisplatin; Drug: Adriamycin; Drug: Cyclophosphamide; Drug: Etoposide; Drug: Melphalan; Procedure: ASCT; Drug: Lenalidomide; Drug: Bortezomib

Interventions

Carfilzomib DRUG

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.

Also known as: Kyprolis

Study Treatment

Thalidomide DRUG

Given by mouth at bedtime: days 1-4 of Induction

Also known as: Thalomid

Study Treatment

Dexamethasone DRUG

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

Also known as: Baycadron

Study Treatment

Daratumumab DRUG

Given by vein: day -1 of induction; days 1 and 8 of Immunological Consolidations; and day 1 of each Maintenance cycle

Also known as: Darzalex

Study Treatment

Cisplatin DRUG

Given by vein: days 1-4 (continuous infusion) of Induction

Also known as: Platinol

Study Treatment

Adriamycin DRUG

Given by vein: days 1-4 (continuous infusion) of Induction

Also known as: Doxorubicin

Study Treatment

Cyclophosphamide DRUG

Given by vein: days 1-4 (continuous infusion) of Induction

Also known as: Cytoxan

Study Treatment

Etoposide DRUG

Given by vein: days 1-4 (continuous infusion) of Induction

Also known as: Eposin

Study Treatment

Melphalan DRUG

Given by vein: days -4 - -1 of Transplant(s)

Study Treatment

ASCT PROCEDURE

day 0 of Transplant(s)

Study Treatment

Lenalidomide DRUG

Given by mouth: days 1-21 of alternating 3-month blocks during Maintenance

Also known as: Revlimid

Study Treatment

Bortezomib DRUG

Given by vein or subcutaneous injection: may be substituted for carfilzomib throughout the study regimen at the discretion of the treating physician

Also known as: Velcade

Study Treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Arkansas: lead
• Janssen, LP: collaborator

Study Sites (1)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Related Publications (1)

• Pawlyn C. High-risk myeloma: a challenge to define and to determine the optimal treatment. Lancet Haematol. 2021 Jan;8(1):e4-e6. doi: 10.1016/S2352-3026(20)30361-6. Epub 2020 Dec 22. No abstract available.

  PMID: 33357481 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; Thalidomide; Dexamethasone; Calcium Dobesilate; daratumumab; Cisplatin; Doxorubicin; Cyclophosphamide; Etoposide; Melphalan; Lenalidomide; Bortezomib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Boronic Acids; Acids, Noncarboxylic; Acids; Boron Compounds; Pyrazines

Study Officials

• Frits van Rhee, MD

  University of Arkansas for Medical Science-Myeloma Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2016
• First Posted: December 28, 2016
• Study Start: July 1, 2017
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2027
• Last Updated: September 10, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)