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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by University of Iowa
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Guido Tricot, University of Iowa
ClinicalTrials.gov Identifier:
NCT01849783
First received: May 6, 2013
Last updated: November 26, 2013
Last verified: November 2013
  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.


Condition Intervention Phase
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
Drug: dexamethasone
Drug: cisplatin
Drug: doxorubicin
Drug: cyclophosphamide
Drug: etoposide
Drug: bortezomib
Drug: thalidomide
Drug: melphalan
Procedure: autologous stem cell transplant
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of Iowa:

Primary Outcome Measures:
  • PFS [ 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 ] [ Designated as safety issue: No ]
    Estimated with the method of Kaplan-Meier and modeled as functions of clinicopathological factors with Cox regression.

  • Severe complications (ICU admission, death), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 [ Time Frame: Up to 4 years ] [ Designated as safety issue: Yes ]
    Frequencies of toxicities will be tabulated on all participants who have completed at least one day of induction therapy. Toxicities will be compared descriptively to historical controls.

  • Percentage of participants able to complete full course of therapy [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Complete response (CR) rate using the International Myeloma Working group uniform response criteria [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Summarized with binomial proportions.

  • Event free survival [ Time Frame: Time from initial study enrollment to progression/relapse of disease or death from any cause, assessed up to 4 years ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    Estimated with the method of Kaplan-Meier and modeled as functions of clinicopathological factors with Cox regression.

  • Overall survival [ Time Frame: Time from initial study enrollment to death from any cause, assessed up to 4 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 41
Study Start Date: April 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Drug: dexamethasone
Given PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: doxorubicin
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: cyclophosphamide
Given IV or PO
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Drug: thalidomide
Given PO
Other Names:
  • Kevadon
  • Synovir
  • THAL
  • Thalomid
Drug: melphalan
Given IV
Other Names:
  • Alkeran
  • CB-3025
  • L-PAM
  • L-phenylalanine mustard
  • L-Sarcolysin
Procedure: autologous stem cell transplant

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.

  Eligibility

Ages Eligible for Study:   65 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01849783

Locations
United States, Iowa
University of Iowa Hospitals and Clinics Recruiting
Iowa City, Iowa, United States, 52242
Contact: Guido J. Tricot    319-356-3425    guido-tricot@uiowa.edu   
Principal Investigator: Guido J. Tricot         
Sponsors and Collaborators
University of Iowa
Investigators
Principal Investigator: Guido Tricot University of Iowa
  More Information

No publications provided

Responsible Party: Guido Tricot, Principal Investigator, University of Iowa
ClinicalTrials.gov Identifier: NCT01849783     History of Changes
Other Study ID Numbers: 201208755, NCI-2013-00883, 10120146, P30CA086862
Study First Received: May 6, 2013
Last Updated: November 26, 2013
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Plasmacytoma
Amyloidosis
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Metabolic Diseases
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Proteostasis Deficiencies
Vascular Diseases
BB 1101
Bortezomib
Cisplatin
Cyclophosphamide
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Doxorubicin
Etoposide
Liposomal doxorubicin
Melphalan
Thalidomide

ClinicalTrials.gov processed this record on October 29, 2014