- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01548573
Tandem Auto Transplantation in Myeloma Patients With <12 Months of Prior Treatment
Tandem Autotransplantation for Multiple Myeloma in Participants With Less Than 12 Months of Preceding Therapy, Incorporating Velcade (Bortezomib) With the Transplant Chemotherapy and During Maintenance
Study Overview
Status
Conditions
Detailed Description
This study is targeted towards patients who have been diagnosed with Multiple Myeloma, POEMS(Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes), or myeloma plus amyloidosis and have had no more than 12 months of prior treatment. Furthermore, participants cannot have had a prior autologous or allogeneic transplant. The study schema consists of one round of induction chemotherapy, two transplants, one round of consolidation chemotherapy, and two years of maintenance treatment. This study design differs from its historical predecessors in the following manner:
- In contrast to Total Therapy II and III, which only allow enrollment of patients with one cycle or one month of treatment prior to enrollment, the proposed study allows enrollment of participants with up to 12 months of prior treatment.
- Induction therapy has been reduced to a single cycle.
- Bortezomib and thalidomide have been added to the transplant regimen.
- Carmustine is added to the second transplant.
- Gemcitabine is added to the second transplant regimen.
- Consolidation treatment has been reduced to a single cycle.
- The first year of maintenance consists of 12 28-day cycles of bortezomib,dexamethasone, and either thalidomide, lenalidomide, or cyclophoshamide. The second year of maintenance therapy consists of lenalidomide and dexamethasone.
- The novel agents thalidomide and bortezomib are not introduced upfront, but only with transplantation, consolidation, and maintenance.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Iowa
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Iowa City, Iowa, United States, 52242
- University of Iowa Holden Comprehensive Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Participants must have had a diagnosis of symptomatic 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 (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) focal plasmacytomas or focal lesions on MRI.
- 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 PI.
- Participants must not have had a prior transplant.
- Participants must be 18-80 years of age at the time of study entry.
- Ejection fraction by ECHO or MUGA of ≥ 40% performed.
- Participants must have adequate pulmonary function studies, > 50% of predicted on mechanical aspects (FEV1, FVC) and diffusion capacity (DLCO) > 50% of predicted (adjusted for hemoglobin). If the participant is unable to complete pulmonary function tests due to disease related pain or condition, a participant may still be enrolled provided that the PI or enrolling investigator documents that the participant is a transplant candidate.
- Participants must have a creatinine < 3 mg/dl and a calculated creatinine clearance >30mL/min. The Cockroft-Gault equation may be used to obtain calculated creatinine clearance.
- Participants must have a performance status of 0-2 based on 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 IRB-approved study ICF (Informed Consent Form).
Exclusion Criteria:
- Prior autologous or allogeneic transplant.
- Platelet count < 30 x 109/L, unless myeloma-related. If MM-related, 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 or creatinine >3 mg/dl.
- Participants must not have a concurrent malignancy unless it can be adequately treated by surgical, non-chemotherapeutic intervention. Participants may have a history of prior malignancy, provided that he/she has not had any treatment 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.
- Women of child-bearing potential must have a documented negative pregnancy test documented within one week of study entry. Women and men of reproductive potential may not participate unless they have agreed, by signing the study ICF, to use effective contraceptive method(s) as outlined in that form.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: Tandem 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 1: 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) Transplant 2: 8 weeks to 6 months after the first transplant, participants will have the second transplant Maintenance: Year 1- VTD (bortezomib, thalidomide, dexamethasone) cycles. Year 2 - VCD (bortezomib, cyclophosphamide, dexamethasone)cycles. |
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given PO
Other Names:
Given IV
Other Names:
Given PO
Other Names:
Given IV
Other Names:
Given IV or PO
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Event-Free Survival (EFS)
Time Frame: 8 years
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To determine whether, in comparison to Total Therapy II, the median Event-Free Survival (EFS) can be increased from 4.8 years to 7.2 years, which represents an increase in median EFS of approximately 50%, based on an intent-to-treat analysis.
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8 years
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Identification of Drug Resistant Genes
Time Frame: 5 years
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To determine whether repeated bone marrow samples analyzed for gene expression profiling (GEP) can identify genes related to drug resistance in myeloma.
The drug resistant genes or the gene products might then be targeted specifically to eradicate myeloma cells surviving tandem transplantation.
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5 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Grade 3 Non-hematologic and Grade 4 Hematologic Serious Adverse Events Associated With the Addition of Bortezomib, Thalidomide, and Dexamethasone Into Autologous Transplant Regimens.
Time Frame: 2 years
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To determine whether bortezomib, thalidomide and dexamethasone with transplant 1 and velcade/gemcitabine with transplant 2 can be safely incorporated into well-tested pre-transplant regimens of high-dose melphalan and carmustine/melphalan in doses equivalent to the BEAM(BCNU, etoposide, arabinoside, melphalan)regimen.
Treatment-related toxicities will be compared to those reported in the literature using similar intensive approaches.
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2 years
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Overall Survival
Time Frame: 10 years
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To determine the median overall survival based on an intent-to-treat analysis, which should exceed 10 years, based on the projected 10-year survival of Total Therapy III, keeping in mind that participants are included in this protocol with up to 12 months of prior therapy.
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10 years
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Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Autonomic Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Anti-Bacterial Agents
- Leprostatic Agents
- Antibiotics, Antineoplastic
- Dexamethasone
- Cyclophosphamide
- Etoposide
- Etoposide phosphate
- Thalidomide
- Melphalan
- Bortezomib
- Doxorubicin
- Liposomal doxorubicin
Other Study ID Numbers
- 201202818
- 7R01CA115399 (NIH)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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