Extramedullary PlasmacytomaPhase 2NCT01849783
Autologous Stem Cell Transplant Followed By Maintenance Therapy in Treating Elderly Patients With Multiple Myeloma
A Phase 2 study testing dexamethasone, cisplatin and doxorubicin in people with Extramedullary Plasmacytoma and Isolated Plasmacytoma of Bone, run by Margarida Magalhaes-Silverman at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 65 to 85 years
- Conditions the study is for
- Extramedullary Plasmacytoma, Isolated Plasmacytoma of Bone, Light Chain Deposition Disease
- What is being tested?
- dexamethasone, cisplatin and doxorubicin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Apr 2013to 30 Sep 2020
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 to 85 years
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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
Show all 10Show fewer
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
About this study
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
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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.
SECONDARY OBJECTIVES:
- 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.
OUTLINE:
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 .
- Conditions
- Extramedullary Plasmacytoma, Isolated Plasmacytoma of Bone, Light Chain Deposition Disease, Primary Systemic Amyloidosis, Stage I Multiple Myeloma, Stage II Multiple Myeloma
- Being tested
- dexamethasone, cisplatin, doxorubicin, cyclophosphamide, etoposide
- Medical subject headings
- Immunoglobulin Light-chain Amyloidosis, Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dexamethasoneDrug
Also called Aeroseb-Dex, Decaderm, Decadron, DM
Given PO
cisplatinDrug
Also called CACP, CDDP, CPDD, DDP
Given IV
doxorubicinDrug
Also called ADM, ADR, Adria, Adriamycin PFS
Given IV
cyclophosphamideDrug
Also called CPM, CTX, Cytoxan, Endoxan
Given IV or PO
etoposideDrug
Also called EPEG, VP-16, VP-16-213
Given IV
bortezomibDrug
Also called LDP 341, MLN341, VELCADE
Given IV
thalidomideDrug
Also called Kevadon, Synovir, THAL, Thalomid
Given PO
melphalanDrug
Also called Alkeran, CB-3025, L-PAM, L-phenylalanine mustard
Given IV
autologous stem cell transplantProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| autologous stem cell transplant | Experimental | 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. Receives: Drug: dexamethasone; Drug: cisplatin; Drug: doxorubicin; Drug: cyclophosphamide; Drug: etoposide; Drug: bortezomib; Drug: thalidomide; Drug: melphalan; Procedure: autologous stem cell transplant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median Progression Free Survival (mPFS)
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.
Measured: 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 Serious Treatment-Related Complications
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.
Measured: 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 Able to Complete Full Course Therapy
Percentage of participants able to complete the full course of therapy.
Measured: Up to 6 years
Secondary outcomes (1)
Mean Change in Quality-Of-Life Indicators Post-Transplant
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.
Measured: Pre-DPACE, Pre-maintenance, every 6 months for up to 2 years during maintenance. Up to 6 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2013 (estimated)
- Study start4 Apr 2013
- Primary completion30 Sep 2020
- Study completion30 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Extramedullary PlasmacytomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Margarida Magalhaes-Silverman
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, Margarida Magalhaes-Silverman, University of Iowa
- Investigators
- Margarida Magalhaes-Silverman, MD, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01849783
- Sponsor's protocol ID
- 201208775
- Other IDs
- 10120146, P30CA086862, NCI-2013-00883
- Status last verified
- Apr 2022
- First submitted
- 6 May 2013
- Last updated
- 11 May 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- Individual data sharing
- No