Single Autologous Transplant Followed by Consolidation and Maintenance for Participants ≥ 65 Years of Age Diagnosed With Multiple Myeloma or a Related Plasma Cell Malignancy
65 Years
85 Years
Both
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
Trial Information
Single Autologous Transplant Followed by Consolidation and Maintenance for Participants ≥ 65 Years of Age Diagnosed With Multiple Myeloma or a Related Plasma Cell Malignancy
PRIMARY OBJECTIVES:
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.
SECONDARY OBJECTIVES:
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.
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: Beginning 2-3 months post-transplant, patients with platelet counts >
80,000/ul 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. Treatment continues in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY YEAR 1: Beginning 6 weeks-3 months after consolidation therapy or 4
weeks to 3 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 or lenalidomide PO once
daily (QD) on days 1-21, 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 up for at least once annually.
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
immunoglobin [Ig]G, 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) focal plasmacytomas or focal
lesions on magnetic resonance imaging (MRI) at the time of diagnosis or study
enrollment , OR the presence of lytic lesions on positron emission tomography
(PET)/computed tomography (CT) scan or skeletal survey at diagnosis or study
enrollment
- Participants must have received no more than 12 months of prior chemotherapy for this
disease; participants may have received prior radiotherapy provided approval has been
obtained from the principal investigator (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
- 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 calculated creatinine clearance >
30 mL/min; the Cockcroft-Gault equation may be used to obtain calculated creatinine
clearance
- 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
- 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
- Recent (=< 6 months) myocardial infarction, unstable angina, difficult to control
congestive heart failure, uncontrolled hypertension, or difficult to control cardiac
arrhythmias
- Participants must not have light chain deposition disease-related renal failure
(creatinine > 2 mg/dl) or creatinine > 3 mg/dl at time of enrollment for any reason
- 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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
PFS
Outcome Description:
Estimated with the method of Kaplan-Meier and modeled as functions of clinicopathological factors with Cox regression.
Outcome Time Frame:
From the start of DPACE for all participants who have had at least one day of protocol treatment, assessed up to 4 years
Safety Issue:
No
Principal Investigator
Guido Tricot
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of Iowa
Authority:
United States: Federal Government
Study ID:
201208755
NCT ID:
NCT01849783
Start Date:
April 2013
Completion Date:
December 2015
Related Keywords:
- 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
- Amyloidosis
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
Name | Location |
|---|---|
| University of Iowa Hospitals and Clinics | Iowa City, Iowa 52242 |
