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

NCT01849783 | Completed Phase 2 Results DMC FDA Drug

• 4 other identifiers: 20120877510120146P30CA086862NCI-2013-00883
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  Up to 6 years

Secondary Outcomes (1)

• Mean Change in Quality-Of-Life Indicators Post-Transplant

  Pre-DPACE, Pre-maintenance, every 6 months for up to 2 years during maintenance. Up to 6 years.

Study Arms (1)

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.

Drug: dexamethasone; Drug: cisplatin; Drug: doxorubicin; Drug: cyclophosphamide; Drug: etoposide; Drug: bortezomib; Drug: thalidomide; Drug: melphalan; Procedure: autologous stem cell transplant

Interventions

dexamethasone DRUG

Given PO

Also known as: Aeroseb-Dex, Decaderm, Decadron, DM, DXM

autologous stem cell transplant

cisplatin DRUG

Given IV

Also known as: CACP, CDDP, CPDD, DDP

autologous stem cell transplant

doxorubicin DRUG

Given IV

Also known as: ADM, ADR, Adria, Adriamycin PFS, Adriamycin RDF

autologous stem cell transplant

cyclophosphamide DRUG

Given IV or PO

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana

autologous stem cell transplant

etoposide DRUG

Given IV

Also known as: EPEG, VP-16, VP-16-213

autologous stem cell transplant

bortezomib DRUG

Given IV

Also known as: LDP 341, MLN341, VELCADE

autologous stem cell transplant

thalidomide DRUG

Given PO

Also known as: Kevadon, Synovir, THAL, Thalomid

autologous stem cell transplant

melphalan DRUG

Given IV

Also known as: Alkeran, CB-3025, L-PAM, L-phenylalanine mustard, L-Sarcolysin

autologous stem cell transplant

autologous stem cell transplant PROCEDURE

autologous stem cell transplant

Eligibility Criteria

• Age: 65 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Margarida Magalhaes-Silverman: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis; Multiple Myeloma

Interventions

Dexamethasone; Calcium Dobesilate; Cisplatin; Doxorubicin; Cyclophosphamide; Etoposide; Bortezomib; Thalidomide; Melphalan

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Boronic Acids; Acids, Noncarboxylic; Acids; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Margarida Magalhaes-Silverman, MD
• Organization: University of Iowa

margarida-silverman@uiowa.edu

319-384-9156

Study Officials

• Margarida Magalhaes-Silverman, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 6, 2013
• First Posted: May 9, 2013
• Study Start: April 4, 2013
• Primary Completion: September 30, 2020
• Study Completion: September 30, 2020
• Last Updated: May 11, 2022
• Results First Posted: May 11, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)