Autologous Stem Cell Transplant Followed By Maintenance Therapy in Treating Elderly Patients With Multiple Myeloma
Overview[ - collapse ][ - ]
Purpose | This phase II trial investigates whether patients >= 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. |
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Condition | 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 |
Intervention | Drug: dexamethasone Drug: cisplatin Drug: doxorubicin Drug: cyclophosphamide Drug: etoposide Drug: bortezomib Drug: thalidomide Drug: melphalan Procedure: autologous stem cell transplant |
Phase | Phase 2 |
Sponsor | University of Iowa |
Responsible Party | University of Iowa |
ClinicalTrials.gov Identifier | NCT01849783 |
First Received | May 6, 2013 |
Last Updated | November 26, 2013 |
Last verified | November 2013 |
Tracking Information[ + expand ][ + ]
First Received Date | May 6, 2013 |
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Last Updated Date | November 26, 2013 |
Start Date | April 2013 |
Estimated Primary Completion Date | December 2015 |
Current Primary Outcome Measures |
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Current Secondary Outcome Measures |
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Descriptive Information[ + expand ][ + ]
Brief Title | Autologous Stem Cell Transplant Followed By Maintenance Therapy in Treating Elderly Patients With Multiple Myeloma |
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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 |
Brief Summary | This phase II trial investigates whether patients >= 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. |
Detailed Description | 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. |
Study Type | Interventional |
Study Phase | Phase 2 |
Study Design | Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment |
Condition |
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Intervention | Drug: dexamethasone Given PO Other Names:
Given IV Other Names:
Given IV Other Names:
Given IV or PO Other Names:
Given IV Other Names:
Given IV Other Names:
Given PO Other Names:
Given IV Other Names:
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Study Arm (s) | 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: VDT-PACE(bortezomib,dexamethasone,thalidomide,cisplatin,doxorubicin,cyclophosphamide, etoposide) Maintenance: Year 1 - VTD (bortezomib, thalidomide, dexamethasone) or VRD (bortezomib,lenalidomide,dexamethasone) cycles. Year 2 - VCD (bortezomib, cyclophosphamide, dexamethasone)cycles. |
Recruitment Information[ + expand ][ + ]
Recruitment Status | Recruiting |
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Estimated Enrollment | 41 |
Estimated Completion Date | December 2015 |
Estimated Primary Completion Date | December 2014 |
Eligibility Criteria | 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 |
Gender | Both |
Ages | 65 Years |
Accepts Healthy Volunteers | No |
Contacts | Not Provided |
Location Countries | United States |
Administrative Information[ + expand ][ + ]
NCT Number | NCT01849783 |
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Other Study ID Numbers | 201208755 |
Has Data Monitoring Committee | Yes |
Information Provided By | University of Iowa |
Study Sponsor | University of Iowa |
Collaborators | National Cancer Institute (NCI) |
Investigators | Principal Investigator: Guido Tricot University of Iowa |
Verification Date | November 2013 |
Locations[ + expand ][ + ]
University of Iowa Hospitals and Clinics | Iowa City, Iowa, United States, 52242 Contact: Guido J. Tricot | 319-356-3425 | guido-tricot@uiowa.eduPrincipal Investigator: Guido J. Tricot Recruiting |
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