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Autologous Stem Cell Transplant Followed By Maintenance Therapy in Treating Elderly Patients With Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT01849783
Recruitment Status : Completed
First Posted : May 9, 2013
Results First Posted : May 11, 2022
Last Update Posted : May 11, 2022
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Margarida Magalhaes-Silverman, University of Iowa

Brief Summary:
This phase II trial investigates whether patients greater than or equal to 65 years of age diagnosed with myeloma or another plasma cell malignancy will have better outcomes with transplant followed by maintenance therapy, as primarily measured by progression-free survival, versus non-transplant approaches.

Condition or disease Intervention/treatment Phase
Extramedullary Plasmacytoma Isolated Plasmacytoma of Bone Light Chain Deposition Disease Primary Systemic Amyloidosis Stage I Multiple Myeloma Stage II Multiple Myeloma Stage III Multiple Myeloma Drug: dexamethasone Drug: cisplatin Drug: doxorubicin Drug: cyclophosphamide Drug: etoposide Drug: bortezomib Drug: thalidomide Drug: melphalan Procedure: autologous stem cell transplant Phase 2

Detailed Description:


I. To evaluate the progression-free survival (PFS) from the start of dexamethasone, cisplatin, Adriamycin (doxorubicin),Cytoxan (cyclophosphamide), etoposide (DPACE) for all participants who have had at least one day of protocol treatment.

II. To evaluate how well such therapy is tolerated in patients mainly over the age of 65 years by assessing severe complications (intensive care unit [ICU] admission, death) and the percentage of participants able to complete the full course of therapy.


I. To evaluate Quality-Of-Life post-transplant using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire QLQ-C30 and QLC-MY20.


INDUCTION THERAPY: Patients receive dexamethasone orally (PO) on days 1-4 and 8-11, cisplatin intravenously (IV) continuously, doxorubicin hydrochloride IV continuously, cyclophosphamide IV, and etoposide IV on days 1-4. Patients then receive pegfilgrastim subcutaneously (SQ) on days 6 and 13 and undergo collection of stem cells when white blood cell (WBC) and cluster of differentiation (CD)34 counts are within program range. Following stem cell collection, patients may receive interim dexamethasone PO on days 1-4, every 14 days at the discretion of the treating physician.

TRANSPLANT: Beginning between 4 weeks to 6 months after the first day of induction therapy, patients receive as transplant conditioning regimen dexamethasone PO on days -4 to -1 and days +2 through +5, bortezomib IV bolus on days -4, -1, 2, and 5, thalidomide PO on days -4 to 5, and melphalan IV on days -4 and -1. Patients undergo autologous peripheral blood stem cell transplant (PBSCT) on day 0. Between transplant and consolidation therapy, patients receive dexamethasone PO on days 1-4 every 21 days and thalidomide PO daily.

CONSOLIDATION THERAPY: If administered, post-transplant consolidation may begin 4-6 weeks after transplant but should occur no more than 4 months later. Most patients will not receive consolidation. Those that do will receive dexamethasone PO on days 1-4 and 8-11, thalidomide PO on days 1-11, bortezomib IV on days 1, 4, 8, and 11, cisplatin IV continuously, doxorubicin hydrochloride IV continuously, cyclophosphamide IV continuously, and etoposide IV continuously on days 1-4.

MAINTENANCE THERAPY YEAR 1: Beginning 6 weeks-6 months after consolidation therapy or 4 weeks to 6 months after transplant if consolidation is skipped, patients receive bortezomib IV bolus on days 1, 4, 15, and 18, thalidomide PO QD on days 1-28, and dexamethasone PO on days 1-4 and 15-18. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY YEAR 2: Patients receive bortezomib IV on days 1, 4, 15, and 18, cyclophosphamide PO or IV on days 1 and 15, and dexamethasone PO QD on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at least once annually at the study center, but serum for MM marker results will be sent to the study site for close monitoring of PFS .

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 41 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Single Autologous Transplant Followed by Consolidation and Maintenance for Participants ≥ 65 Years of Age Diagnosed With Multiple Myeloma or a Related Plasma Cell Malignancy
Actual Study Start Date : April 4, 2013
Actual Primary Completion Date : September 30, 2020
Actual Study Completion Date : September 30, 2020

Arm Intervention/treatment
Experimental: autologous stem cell transplant

Induction : DPACE(dexamethasone,cisplatin,doxorubicin,cyclophosphamide,etoposide) chemotherapy plus stem cell collection. Additional stem cell collection and/or chemotherapy may be required.

After collection, participants will receive dexamethasone x 4 days every 14 days.

Transplant: The transplant preparative regimen will be bortezomib/thalidomide/dexamethasone/melphalan.

Once recovered, participants start thalidomide daily and dexamethasone x 4 days every 21 days.

Consolidation (if administered): VDT-PACE(bortezomib,dexamethasone,thalidomide,cisplatin,doxorubicin,cyclophosphamide, etoposide)

Maintenance: Year 1 - VTD (bortezomib, thalidomide, dexamethasone) cycles. Year 2 - VCD (bortezomib, cyclophosphamide, dexamethasone)cycles.

Drug: dexamethasone
Given PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM

Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP

Drug: doxorubicin
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF

Drug: cyclophosphamide
Given IV or PO
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana

Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213

Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341

Drug: thalidomide
Given PO
Other Names:
  • Kevadon
  • Synovir
  • THAL
  • Thalomid

Drug: melphalan
Given IV
Other Names:
  • Alkeran
  • CB-3025
  • L-PAM
  • L-phenylalanine mustard
  • L-Sarcolysin

Procedure: autologous stem cell transplant

Primary Outcome Measures :
  1. Median Progression Free Survival (mPFS) [ Time Frame: From the start of DPACE for all participants who have had at least one day of protocol treatment. Up to 6 years. ]
    PFS is defined as the time from the start of DPACE to the date of first documentation of disease progression as assessed by the International Myeloma Working Group response criteria or death due to any cause. Progression is defined using the International Myeloma Working Group response criteria, an increase of greater than or equal to 25% from the lower response value.

  2. Percentage of Participants With Serious Treatment-Related Complications [ Time Frame: From the start of DPACE for all participants who have had at least one day of protocol treatment. Up to 6 years. ]
    Percentage of participants with severe complications defined at ICU admission and death, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.

  3. Percentage of Participants Able to Complete Full Course Therapy [ Time Frame: Up to 6 years ]
    Percentage of participants able to complete the full course of therapy.

Secondary Outcome Measures :
  1. Mean Change in Quality-Of-Life Indicators Post-Transplant [ Time Frame: Pre-DPACE, Pre-maintenance, every 6 months for up to 2 years during maintenance. Up to 6 years. ]
    Measured using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) and Multiple Myeloma module (QLQ-MY20). The EORTC QLQ-C30 includes functional scales (physical, role, emotional, cognitive, and social) and global health status. The EORTC QLQ-MY20 includes disease symptoms and treatment side effects scales. Scores are averaged and transformed to 0-100 scale. For functional and global health status, a positive change from baseline (pre-DPACE) indicates improvement whereas for the symptom scales a negative change from baseline (pre-DPACE) indicates improvement.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   65 Years to 85 Years   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Participants must have had a diagnosis of symptomatic multiple myeloma (MM), MM + amyloidosis, or POEMS (osteosclerotic myeloma: polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) requiring treatment; participants with a previous history of smoldering myeloma will be eligible if there is evidence of progressive disease requiring chemotherapy; Note that study participants do not need to have active disease at the time of study entry, as participants may have received up to 12 months of prior chemotherapy, which might have induced a response
  • Protein criteria must be present at diagnosis (quantifiable M-component of IgG, IgA, IgD, or IgE and/or urinary kappa or lambda light chain, Bence-Jones protein, or Free Kappa Light Chain or Free Lambda Light Chain) in order to evaluate response. Non-secretory participants are eligible provided the participant has > 20% plasmacytosis OR multiple (≥3) plasmacytomas or lesions on MRI at the time of diagnosis or study enrollment , OR the presence of lesions on PET/CT scan or skeletal survey at diagnosis or study enrollment.
  • Participants must have received ≤12 months of prior chemotherapy for this disease without evidence of progressive disease with treatment. Participants may have received prior radiotherapy provided approval has been obtained from the PI. Participants with a history of radiation who have a platelet count <150,000 due to radiation (disease, chemo, and other factors have been ruled out) will be excluded from this study.
  • Participants must not have had a prior transplant
  • Participants must be 65-85 years of age at the time of study entry.
  • Ejection fraction by echocardiogram (ECHO) or multigated acquisition scan (MUGA) of >= 40% performed
  • Participants must have adequate pulmonary function studies (PFTs), >= 50% of predicted on mechanical aspects (forced expiratory volume in 1 second [FEV^1}, forced vital capacity [FVC]) and diffusion capacity (diffusion capacity of the lung for carbon monoxide [DLCO]) >= 50% of predicted (adjusted for hemoglobin); if the participant is unable to complete pulmonary function tests (PFTs) due to disease-related pain or other circumstances that make it difficult to reliably perform PFTs, documentation of pulmonary function adequate for transplant will occur via a CT scan without evidence of major pulmonary disease, and arterial blood gas results
  • Participants must have a creatinine < 3 mg/dl and a GFR >30mL/min/1.73m2
  • Participants must have a performance status of 0-2 based on Eastern Cooperative Oncology Group (ECOG) criteria; participants with a poor performance status (3-4) based solely on bone pain will be eligible, provided there is documentation to verify this
  • Participants must sign the most current institutional review board (IRB)-approved study (informed consent form) ICF

Exclusion Criteria:

  • Prior autologous or allogeneic transplant
  • Progressive disease on prior treatment
  • Platelet count < 30 x 10^9/L, unless myeloma-related; if MM-related (hypercellular marrow biopsy of > 80% and packed with at least 80% plasma cells) the enrolling investigator must document this
  • > Grade 3 neuropathy
  • Known hypersensitivity to bortezomib, boron, or mannitol
  • Uncontrolled diabetes on appropriate therapy
  • Recent (=< 6 months) myocardial infarction, unstable angina, difficult to control congestive heart failure, uncontrolled hypertension on appropriate therapy, or difficult-to-control cardiac arrhythmias
  • Participants must not have a creatinine >3 mg/dl or a GFR <30mL/min/1.73m2.
  • Participants must not have a concurrent malignancy unless it can be adequately treated by non-chemotherapeutic intervention; participants may have a history of prior malignancy, provided that he/she has not had any chemotherapy within 365 days of study entry AND that life expectancy exceeds 5 years at the time of study entry
  • Participants must not have life-threatening co-morbidities

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01849783

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United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
Sponsors and Collaborators
Margarida Magalhaes-Silverman
National Cancer Institute (NCI)
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Principal Investigator: Margarida Magalhaes-Silverman, MD University of Iowa
  Study Documents (Full-Text)

Documents provided by Margarida Magalhaes-Silverman, University of Iowa:
Informed Consent Form  [PDF] February 27, 2018

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Responsible Party: Margarida Magalhaes-Silverman, Principal Investigator, University of Iowa
ClinicalTrials.gov Identifier: NCT01849783    
Other Study ID Numbers: 201208775
P30CA086862 ( U.S. NIH Grant/Contract )
NCI-2013-00883 ( Other Identifier: NCI CTRP )
First Posted: May 9, 2013    Key Record Dates
Results First Posted: May 11, 2022
Last Update Posted: May 11, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Immunoglobulin Light-chain Amyloidosis
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Proteostasis Deficiencies
Metabolic Diseases
Liposomal doxorubicin
Etoposide phosphate
Immunosuppressive Agents
Immunologic Factors