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

NCT01852799 | Completed Phase 2 Results DMC

• 1 other identifier: 26866138MMY2074
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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:

1. 1.Subgroup analysis for the change from baseline in biochemical bone marker based on whether or not Bisphosphonate was used.
2. 2.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);
3. 3.To observe the effect of bortezomib on bone mineral density (BMD) as measured by repeated quantitative CT-scan;
4. 4.The evaluation of Skeletal related events (SRE) and appearance of new bone lesions;
5. 5.To determine progression free survival (PFS), 1 year survival, overall survival and safety profile following treatment with PAD and ASCT as first-line therapy.

Conditions

Multiple Myeloma

Keywords

Multiple myeloma; PAD; ASCT; Bone metabolites; Bone marker

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to Cycle 4 with 28 days per cycle

Secondary Outcomes (2)

• Measurement of Bone Mineral Density

  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

• Skeletal Related Events' Evaluation

  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 Outcomes (3)

• Evaluation of Responses

  At baseline, on day 28 of cycles 4, and after 4, 6, 12 and 18 months of follow-up

• Safety Evaluation

  Starting with informed consent signature through study completion, an average of 1 year

• Evaluation of Responses(PFS)

  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

Study Arms (1)

PAD Followed by ASCT

EXPERIMENTAL

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.

Drug: PAD Followed by ASCT

Interventions

PAD Followed by ASCT DRUG

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.

Also known as: Induction Therapy (4 cycles), ASCT

PAD Followed by ASCT

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shanghai Changzheng Hospital: lead

Study Sites (1)

Shanghai Changzheng Hospital

Shanghai, Shanghai Municipality, China

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics

Results Point of Contact

• Title: Jian Hou, PhD
• Organization: Shanghai Changzheng Hospital

houjian@medmail.com.cn

86021-63610109-73221

Study Officials

• Jian Hou, PhD

  Shanghai Changzheng Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician, Professor of Shanghai Changzheng Hospital

Study Record Dates

• First Submitted: April 28, 2013
• First Posted: May 14, 2013
• Study Start: December 1, 2012
• Primary Completion: September 1, 2016
• Study Completion: January 1, 2017
• Last Updated: August 10, 2018
• Results First Posted: August 10, 2018

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)