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A Study of PAD Followed by Autologous Stem Cell Transplantation (ASCT) to Treat Newly Diagnosed Multiple Myeloma

Primary Purpose

Multiple Myeloma

Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
PAD Followed by ASCT
Sponsored by
Shanghai Changzheng Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple myeloma, PAD, ASCT, Bone metabolites, Bone marker

Eligibility Criteria

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

Inclusion Criteria:

  1. Man or woman aged 18 to 65 years old;
  2. Subjects are newly diagnosed MM patients which are scheduled by the investigators to be treated with vincristine, adriamycin and dexamethasone standard therapy. Stage II/III (according to Durie and Salmon criteria) with skeletal involvement, such as bone pain, bone lytic lesions, diffuse osteoporosis or pathologic fractures;
  3. Life expectancy > 3 months;

  4. Patient has measurable disease in which to capture response, defined as one or more of the following;

    • Serum M-protein level >10.0 g/L measured by serum protein electrophoresis or immunoglobulin electrophoresis; or
    • Urinary M-protein excretion > 1 g/24 hours; or
    • Bone marrow plasmacytosis of > 30% by bone marrow aspirate and/or biopsy; or
    • Serum free light chains (by the Freelite test) > 2 X the upper limit of normal (ULN), in the absence of renal failure.
  5. Performance status (PS) of ECOG ≤2.0, unless PS of 3-4 based solely on bone pain;
  6. Patients must have a Platelets count≥50×109 cells /L; Absolute neutrophil count (ANC)≥0.75×109 cells /L;
  7. Patients must have adequate hepatic function defined as Alanine transaminase(ALT) ≤ 2.5 × upper limit of normal(ULN); Aspartate transaminase (AST) ≤2.5×ULN; Total bilirubin ≤2×ULN;
  8. Patients must have adequate renal function defined as creatinine clearance >30 ml /min;
  9. Subjects (or their legally acceptable representatives) must have signed a informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.

Exclusion Criteria:

  1. Non-secretory MM, unless the patient has measurable lesions on computed tomography (CT), magnetic resonance imaging (MRI) and/or positron emission tomography (PET);
  2. Peripheral neuropathy or neuropathy pain grade 2 or high as defined by National Cancer Institute Common Terminology Criteria for Adverse Events(NCI CTCAE) Version 3;
  3. Uncontrolled or severe cardiovascular disease, including myocardial infarction (MI ) within 6 months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis;
  4. History of allergy reaction attributable to compounds containing boron or mannitol;
  5. Any serious, active disease or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol or the investigator's decision;
  6. Concurrent treatment with another investigational agent;
  7. Female subject who is pregnant or breast-feeding.

Sites / Locations

  • Shanghai Changzheng Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PAD Followed by ASCT

Arm Description

Drug: Bortezomib, Adriamycin (Doxorubicin) /Epidoxorubicin(EPI), Dexamethasone. After received induction therapy, patients will proceed to receive ASCT based on the willing of the patients and the decision of the investigators.

Outcomes

Primary Outcome Measures

Bone Formation Markers Measurement
The bone formation marker- bone alkaline phosphatase(bALP) and osteoblast inhibitor- Dickkopf-1(DKK-1）are measured on serum samples by ELISA methodology at baseline, on day 28 of cycles 1,4, and after 4, 6, 12 and 18 months of follow-up or until start of alternative multiple myeloma(MM) treatment, if earlier.

Secondary Outcome Measures

Measurement of Bone Mineral Density
The effect on bone mineral density（BMD） will be measured by quantitative analysis of qCT scans of the intra-individual same region [lumbar spine and hip] at baseline, on day 28 of cycles 4, and after 4, 6, 12 and 18 months of follow-up or until start of alternative MM treatment, if earlier.
Skeletal Related Events' Evaluation
Skeletal survey of the skeleton using plain radiography will be performed at baseline, on day 28 of cycle 4, and after 6, 12 and 18 months of follow-up or until start of alternative MM treatment, if earlier. SREs, such as pathological fractures, need for radiation therapy or surgery will be recorded at the time of the event.

Full Information

First Posted
April 28, 2013
Last Updated
November 11, 2017
Sponsor
Shanghai Changzheng Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01852799
Brief Title
A Study of PAD Followed by Autologous Stem Cell Transplantation (ASCT) to Treat Newly Diagnosed Multiple Myeloma
Official Title
A Phase 2, Multicenter, Single Arm Study to Evaluate the Effect of PAD Followed by Autologous Stem-cell Transplantation(ASCT) on the Concentrations of Bone Metabolites in Patients With Newly Diagnosed Multiple Myeloma(MM)
Study Type
Interventional

2. Study Status

Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
December 2012 (undefined)
Primary Completion Date
September 2016 (Actual)
Study Completion Date
January 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Changzheng Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a multicentre; single arm study in subjects with newly diagnosed multiple myeloma. The primary objectives of this study is to assess the effect of bortezomib combination therapy (PAD regimen) followed by ASCT on bone metabolites in patients with newly diagnosed multiple myeloma, as measured by ELISA methodology as previously described analyzing the change in biochemical bone marker compared with the baseline value: bone formation marker- bone alkaline phosphatase(bALP) and osteoblast inhibitor- Dickkopf-1(DKK-1）. The secondary objectives of this study are: Subgroup analysis for the change from baseline in biochemical bone marker based on whether or not Bisphosphonate was used. Assessment of other bone markers parameters: bone formation marker -carboxy terminal propeptide of type I procollagen (PICP); bone resorption markers -carboxy terminal telopeptide region of type I collagen ( ICTP); osteoclast stimulators -osteoprotegerin(OPG), soluble receptor activator of nuclear factor kappaB ligand(sRANKL); To observe the effect of bortezomib on bone mineral density (BMD) as measured by repeated quantitative CT-scan; The evaluation of Skeletal related events (SRE) and appearance of new bone lesions; To determine progression free survival (PFS), 1 year survival, overall survival and safety profile following treatment with PAD and ASCT as first-line therapy.
Detailed Description
After providing written informed consent, subjects will be evaluated for eligibility during a 14-day screening period. Eligible subjects will receive 4 cycles PAD treatment prior to ASCT. Bisphosphonate therapy can be administered as medically indicated and according to local practice. After the end of the treatment phase, there will be 18 months follow-up period for every patient with visits at 4, 6, 12 and 18 months after the end of the treatment phase. In case the disease progresses before completing the 18 months of follow-up and once the subject started alternative MM treatment, study assessments will stop, except for survival follow-up which will be collected every 6 months by either a telephone call or a visit to the study site. The follow-up for survival will continue for all subjects until the last subject has completed follow-up. One interim analysis of efficacy and safety will be performed when all subjects have achieved the end of treatment. Safety will be assessed by the monitoring of adverse events, physical examination, vital signs measurements and clinical laboratory tests.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Multiple myeloma, PAD, ASCT, Bone metabolites, Bone marker

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
PAD Followed by ASCT
Arm Type
Experimental
Arm Description
Drug: Bortezomib, Adriamycin (Doxorubicin) /Epidoxorubicin(EPI), Dexamethasone. After received induction therapy, patients will proceed to receive ASCT based on the willing of the patients and the decision of the investigators.
Intervention Type
Drug
Intervention Name(s)
PAD Followed by ASCT
Other Intervention Name(s)
Induction Therapy (4 cycles), ASCT
Intervention Description
Drug: Bortezomib, Bortezomib (1.3mg/m2, iv, on day 1, 4, 8, 11, of each 28 day cycle) Drug: Adriamycin (Doxorubicin) /EPI, Adriamycin (Doxorubicin) (9 mg/m2, iv, on days 1-4 of each 28 day cycle) or EPI (15mg/m2, iv, on days 1-4 of each 28 day cycle) Drug: Dexamethasone, Dexamethasone (20mg, iv, on days 1-4, 8-11of each 28 day cycle) After received induction therapy, patients will proceed to receive ASCT based on the willing of the patients and the decision of the investigators.
Primary Outcome Measure Information:
Title
Bone Formation Markers Measurement
Description
The bone formation marker- bone alkaline phosphatase(bALP) and osteoblast inhibitor- Dickkopf-1(DKK-1）are measured on serum samples by ELISA methodology at baseline, on day 28 of cycles 1,4, and after 4, 6, 12 and 18 months of follow-up or until start of alternative multiple myeloma(MM) treatment, if earlier.
Time Frame
Up to Cycle 4 with 28 days per cycle
Secondary Outcome Measure Information:
Title
Measurement of Bone Mineral Density
Description
The effect on bone mineral density（BMD） will be measured by quantitative analysis of qCT scans of the intra-individual same region [lumbar spine and hip] at baseline, on day 28 of cycles 4, and after 4, 6, 12 and 18 months of follow-up or until start of alternative MM treatment, if earlier.
Time Frame
At baseline, on day 28 of cycles 1,4, and after 4, 6, 12 and 18 months of follow-up or until start of alternative MM treatment
Title
Skeletal Related Events' Evaluation
Description
Skeletal survey of the skeleton using plain radiography will be performed at baseline, on day 28 of cycle 4, and after 6, 12 and 18 months of follow-up or until start of alternative MM treatment, if earlier. SREs, such as pathological fractures, need for radiation therapy or surgery will be recorded at the time of the event.
Time Frame
At baseline, on day 28 of cycles 4, and after 4, 6, 12 and 18 months of follow-up or until start of alternative MM treatment
Other Pre-specified Outcome Measures:
Title
Evaluation of Responses
Description
Evaluation of responses was performed every cycle. Responses were assessed according to the european group for blood and marrow transplantation（EBMT） criteria (An attempt will be made to collect data for the assessment of stringent complete response (sCR) if these data are available.). Other efficacy parameters including PFS and 1-year overall survival rate and overall survival will be evaluated by normal methodology. According to EBMT criteria, responses were assessed by changes in the level of the serum paraprotein and/or urinary light chain excretion.The specific assessment rules may refer to EBMT criteria for MM.
Time Frame
At baseline, on day 28 of cycles 4, and after 4, 6, 12 and 18 months of follow-up
Title
Safety Evaluation
Description
Safety evaluations will be based on scheduled physical examinations, Eastern Cooperative Oncology Group(ECOG) scores, vital signs (blood pressure, heart rate) and clinical laboratory tests.
Time Frame
Starting with informed consent signature through study completion, an average of 1 year
Title
Evaluation of Responses(PFS)
Description
Efficacy parameters PFS will be evaluated by normal methodology. PFS =（date of signing informed consent form minus the date of first documented progression or date of death from any cause plus 1）/30.5（months）
Time Frame
From date of signing informed consent form until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Man or woman aged 18 to 65 years old; Subjects are newly diagnosed MM patients which are scheduled by the investigators to be treated with vincristine, adriamycin and dexamethasone standard therapy. Stage II/III (according to Durie and Salmon criteria) with skeletal involvement, such as bone pain, bone lytic lesions, diffuse osteoporosis or pathologic fractures; Life expectancy > 3 months; Patient has measurable disease in which to capture response, defined as one or more of the following; Serum M-protein level >10.0 g/L measured by serum protein electrophoresis or immunoglobulin electrophoresis; or Urinary M-protein excretion > 1 g/24 hours; or Bone marrow plasmacytosis of > 30% by bone marrow aspirate and/or biopsy; or Serum free light chains (by the Freelite test) > 2 X the upper limit of normal (ULN), in the absence of renal failure. Performance status (PS) of ECOG ≤2.0, unless PS of 3-4 based solely on bone pain; Patients must have a Platelets count≥50×109 cells /L; Absolute neutrophil count (ANC)≥0.75×109 cells /L; Patients must have adequate hepatic function defined as Alanine transaminase(ALT) ≤ 2.5 × upper limit of normal(ULN); Aspartate transaminase (AST) ≤2.5×ULN; Total bilirubin ≤2×ULN; Patients must have adequate renal function defined as creatinine clearance >30 ml /min; Subjects (or their legally acceptable representatives) must have signed a informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. Exclusion Criteria: Non-secretory MM, unless the patient has measurable lesions on computed tomography (CT), magnetic resonance imaging (MRI) and/or positron emission tomography (PET); Peripheral neuropathy or neuropathy pain grade 2 or high as defined by National Cancer Institute Common Terminology Criteria for Adverse Events(NCI CTCAE) Version 3; Uncontrolled or severe cardiovascular disease, including myocardial infarction (MI ) within 6 months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis; History of allergy reaction attributable to compounds containing boron or mannitol; Any serious, active disease or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol or the investigator's decision; Concurrent treatment with another investigational agent; Female subject who is pregnant or breast-feeding.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jian Hou, PhD
Organizational Affiliation
Shanghai Changzheng Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai Changzheng Hospital
City
Shanghai
State/Province
Shanghai
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Study of PAD Followed by Autologous Stem Cell Transplantation (ASCT) to Treat Newly Diagnosed Multiple Myeloma

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