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

Primary Purpose

Extramedullary Plasmacytoma, Isolated Plasmacytoma of Bone, Light Chain Deposition Disease

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
dexamethasone
cisplatin
doxorubicin
cyclophosphamide
etoposide
bortezomib
thalidomide
melphalan
autologous stem cell transplant
Sponsored by
Margarida Magalhaes-Silverman
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Extramedullary Plasmacytoma

Eligibility Criteria

65 Years - 85 Years (Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Iowa Hospitals and Clinics

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

autologous stem cell transplant

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
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.
Percentage of Participants Able to Complete Full Course Therapy
Percentage of participants able to complete the full course of therapy.

Secondary Outcome Measures

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.

Full Information

First Posted
May 6, 2013
Last Updated
April 17, 2022
Sponsor
Margarida Magalhaes-Silverman
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01849783
Brief Title
Autologous Stem Cell Transplant Followed By Maintenance Therapy in Treating Elderly Patients With Multiple Myeloma
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
April 4, 2013 (Actual)
Primary Completion Date
September 30, 2020 (Actual)
Study Completion Date
September 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Margarida Magalhaes-Silverman
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Data Monitoring Committee
Yes

5. Study Description

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.
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: 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 .

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
autologous stem cell transplant
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
dexamethasone
Other Intervention Name(s)
Aeroseb-Dex, Decaderm, Decadron, DM, DXM
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
cisplatin
Other Intervention Name(s)
CACP, CDDP, CPDD, DDP
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
doxorubicin
Other Intervention Name(s)
ADM, ADR, Adria, Adriamycin PFS, Adriamycin RDF
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
CPM, CTX, Cytoxan, Endoxan, Endoxana
Intervention Description
Given IV or PO
Intervention Type
Drug
Intervention Name(s)
etoposide
Other Intervention Name(s)
EPEG, VP-16, VP-16-213
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
bortezomib
Other Intervention Name(s)
LDP 341, MLN341, VELCADE
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
thalidomide
Other Intervention Name(s)
Kevadon, Synovir, THAL, Thalomid
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
melphalan
Other Intervention Name(s)
Alkeran, CB-3025, L-PAM, L-phenylalanine mustard, L-Sarcolysin
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
autologous stem cell transplant
Primary Outcome Measure Information:
Title
Median Progression Free Survival (mPFS)
Description
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.
Time Frame
From the start of DPACE for all participants who have had at least one day of protocol treatment. Up to 6 years.
Title
Percentage of Participants With Serious Treatment-Related Complications
Description
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.
Time Frame
From the start of DPACE for all participants who have had at least one day of protocol treatment. Up to 6 years.
Title
Percentage of Participants Able to Complete Full Course Therapy
Description
Percentage of participants able to complete the full course of therapy.
Time Frame
Up to 6 years
Secondary Outcome Measure Information:
Title
Mean Change in Quality-Of-Life Indicators Post-Transplant
Description
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.
Time Frame
Pre-DPACE, Pre-maintenance, every 6 months for up to 2 years during maintenance. Up to 6 years.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Margarida Magalhaes-Silverman, MD
Organizational Affiliation
University of Iowa
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Iowa Hospitals and Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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