Multiple MyelomaPhase 2NCT01660633
Safety & Efficacy Study High Dose Evomela Injection for MA Conditioning in MM Patients With Autologous Transplantation
A Phase 2 study testing High-Dose Melphalan HCL for Injection (Propylene Glycol-Free) and Autologous Transplantation in people with Multiple Myeloma, run by Acrotech Biopharma Inc. at 6 sites in United States.
Trial summary
The purpose of this trial is to confirm the safety and efficacy of high-dose Melphalan HCL for Injection (Propylene Glycol-Free) as a myeloablative conditioning regimen in multiple myeloma patients (MM) undergoing autologous transplantation. Read more about this study
- Who is it for?
- Ages Up to 70 years
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- High-Dose Melphalan HCL for Injection (Propylene Glycol-Free) and Autologous Transplantation
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 61 participants
- Where
- 6 sitesUnited States
- Study dates
- Dec 2012to Aug 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with symptomatic MM based on IMWG guidelines requiring treatment who are eligible for ASCT.
- Patients who are 70 years of age or younger at time of transplant. Patients older than 70 years of age may be enrolled on a case-by-case basis if the patient meets local institutional criteria to receive a total melphalan dose of 200 mg/m2 as a conditioning regimen and if approved by the medical monitor.
- Patients with an adequate autologous graft, defined as an unmanipulated, cryopreserved, peripheral blood stem cell graft containing at least 2 × 106 CD34+ cells/kg based on patient body weight.
- Patients with adequate organ function as measured by:
- Cardiac function: Left ventricular ejection fraction at rest >40% (documented within 8 weeks prior to Day -3).
- Hepatic function: Bilirubin <2 × the upper limit of normal and alanine aminotransferase (ALT)/aspartate aminotransferase (AST) <3 × upper limit of normal.
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- Renal function: Creatinine clearance >40 mL/minute (measured or calculated/estimated).
- Pulmonary function: Carbon monoxide diffusing capacity (DLCO)corrected for hemoglobin (Hgb), forced expiratory volume in 1 second (FEV1), forced expiratory vital capacity (FVC), and oxygen saturation >92% on room air (documented within 4 weeks prior to Day -3).
- Patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
Who cannot join
- Patients with smoldering MM not requiring therapy.
- Patients with plasma cell leukemia.
- Patients with systemic amyloid light chain amyloidosis.
- Patients with uncontrolled hypertension.
- Patients with an active bacterial, viral, or fungal infection.
- Patients with a life expectancy of < 6 months.
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- Patients with prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent >5 years previously will be allowed. Cancer treated with curative intent <5 years previously will not be allowed unless approved by the medical monitor.
- Female patients who are pregnant or breastfeeding.
- Female patients of childbearing potential who are unwilling to use adequate contraceptive techniques during and for 3 months following study treatment with Melphalan HCl for Injection (Propylene Glycol-Free).
- Patients seropositive for Human Immunodeficiency Virus(HIV).
- Patients who are unwilling to provide informed consent.
- Patients receiving other concurrent anticancer therapy (including chemotherapy, radiation, hormonal treatment, or immunotherapy, but excluding corticosteroids) within 30 days prior to the ASCT or planning to receive any of these treatments prior to Day +30.
- Patients concurrently participating in any other clinical study involving ASCT.
- Patients who are hypersensitive or intolerant to any component of the study drug formulation.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Rush University Medical Center
Chicago, Illinois, 60612
University of Kansas Medical Center
Fairway, Kansas, 66205
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792
Medical College of Wisconsin/Froedtert Hospital
Milwaukee, Wisconsin, 53226
Washington University School of Medicine
St Louis, Missouri, 63110
University of Massachusetts
Worcester, Massachusetts, 01655
About this study
Official title: A Phase IIb, Multicenter, Open-Label, Safety and Efficacy Study of High Dose Melphalan HCL for Injection (Propylene Glycol-Free)for Myeloablative Conditioning in Multiple Myeloma Patients Undergoing Autologous Transplantation
The purpose of this trial is to confirm the safety and efficacy of high-dose Melphalan HCL for Injection (Propylene Glycol-Free) as a myeloablative conditioning regimen in multiple myeloma patients (MM) undergoing autologous transplantation.
Read the detailed description
The sponsor of the current study is now Acrotech Biopharma, divested from Spectrum Pharmaceuticals Inc. (Spectrum), which licensed the Melphalan HC1 for Injection (Propylene Glycol-Free) product from Ligand Pharmaceuticals , formerly CyDex Pharmaceuticals, Inc. (CyDex). This new injectable form of melphalan HCL incorporates Captisol®, β cyclodextrin sulfobutyl ether sodium salts (also known as [SBE]7m-β-CD), into the product. Captisol is present to facilitate the use of an all aqueous diluent (normal saline) for reconstitution and administration of the freeze-dried product in place of the propylene glycol-ethanol diluent necessary for the currently used melphalan intravenous product. Captisol provides for solubilization and improved stability of the all aqueous reconstituted and diluted infusion solution.
This is the second of two studies supporting product registration. This study will be a multicenter study of high-dose Melphalan HCL for Injection (Propylene Glycol-Free) conducted in 60 patients who have symptomatic MM and qualify for autologous stem cell transplantation (ASCT).
During the Study Period, patients will receive 100mg/m2 of either Melphalan HCL for Injection (Propylene Glycol-Free) on Day -3 and on Day -2 for a total dose of 200mg/m2. Blood samples (5 timepoints post infusion) for population pharmacokinetic (PK) evaluation will be withdrawn through an indwelling i.v. cannula on the first day of administration of melphalan (Day -3) for all patients and then additional blood samples (2 timepoints post infusion) drawn in a subset of patients on the second day of melphalan administration (Day -2).
Following one day of rest after the high dose myeloablative conditioning (Day -1), patients will receive an autologous graft (Day 0).
- Conditions
- Multiple Myeloma
- Being tested
- High-Dose Melphalan HCL for Injection (Propylene Glycol-Free), Autologous Transplantation
- Keywords
- Multiple Myeloma, High-Dose Melphalan, Propylene Glycol-Free, Autologous Stem Cell Transplantation, Captisol
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High-Dose Melphalan HCL for Injection (Propylene Glycol-Free)Drug
Also called Evomela, Alkeran
200 mg melphalan/m2 will be divided into two separate, consecutive doses of 100 mg/m2 administered on day -3 and day -2 prior to ASCT. The High-Dose Melphaln HCL for Injection (Propylene Glycol-Free) will be reconstituted to 5 mg/mL (also containing 270 mg/mL of Captisol®). The Melphalan HCL for Injection (Propylene Glycol Free) will be further diluted with normal saline to a concentration of no greater than 0.45 mg/mL and infused over 30 minutes ( + or - 3 minutes)via a central venous catheter.
Autologous TransplantationOther
Also called Hematopoietic stem cell transplantation
Patients who are myeloablative conditioning in multiple myeloma undergoing autologous transplantation( patients own blood-forming stem cells are collected to replace diseased bone marrow or bone marrow damaged by cancer treatment)
| Study group | Role | What they receive |
|---|---|---|
| High-Dose Melphalan HCL for Injection (Propylene Glycol-Free) | Other | Subjects will receive only High-Dose Melphalan HCL for Injection (Propylene Glycol-free) at 200mg/m2 (100mg/m2/day for two days). Receives: Drug: High-Dose Melphalan HCL for Injection (Propylene Glycol-Free); Other: Autologous Transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
AE coding will be performed using the MedDRA Version 11.0 or greater. The severity of the toxicities will be graded according to the NCI CTCAE Version 4.0 whenever possible. AEs occurring when treatment starts on Day -3 through Day + 100 will be recorded in the AE section of the eCRF and causality will be assigned by the Principal Investigator.
Measured: Up to Day +100
Mucositis Severity according to World Health Organization Scoring System
The baseline measurement will be the last assessment prior to receiving the first dose of study treatment. The on-treatment period will be defined as the day after the first dose of study treatment to 30 days after the last dose of study treatment. The incidence of severe mucositis (WHO Grade 3 or 4) will be summarized by frequencies and percentages. In addition, the incidence of oral mucositis will be summarized by WHO grade. Time from start of the first dose of study medication to peak oral mucositis score will also be calculated.
Measured: Until Day +30
Mouth Pain Scores according to a Visual Analog Scale
Baseline VAS for mouth pain and dysphagia will be the VAS score collected prior to receiving the first dose of study medication. Analyses of changes and/or percent changes from baseline in the VAS scores will be analyzed for each time point collected during the 30 day on-treatment period. The minimum and maximum VAS scores during the 30 day on-treatment period will also be calculated for mouth pain and dysphagia, and the time to the minimum and maximum VAS scores will be summarized descriptively.
Measured: Until Day +30
Treatment Related Mortality
TRM, which is defined as death not due to disease progression before Day +90/+100, will be calculated. This outcome measure will be summarized by the cumulative incidence estimated with 95% confidence intervals.
Measured: Up to Day +100
Secondary outcomes (5)
MM response according to International Myeloma Working Group (IMWG) criteria.
Definition of active MM, clonal bone marrow plasma cells >10% or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following CRAB features and myeloma-defining events: Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder and one or more biomarkers of malignancy (MDEs) defined in the criteria.
Measured: At the Day +100 visit
Myeloablation
Absolute neutrophil count (ANC) <0.5 × 109/L, absolute lymphocyte count (ALC) <0.1 × 109/L, platelet count <20,000/mm3, or bleeding requiring transfusion.
Measured: Up to Day +30
Neutrophil engraftment
ANC >0.5 × 109/L × first 3 consecutive daily assessments
Measured: Up to Day +100
Platelet engraftment
Untransfused platelet measurement >20,000/mm3 × first 3 consecutive daily assessments
Measured: Up to Day +100
Non-engraftment
Failure to reach an ANC >0.5 × 109/L × 3 consecutive daily assessments by Day +100.
Measured: Up to Day +100
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2012 (estimated)
- Study startDec 2012
- Primary completionFeb 2014
- Study completionAug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- Acrotech Biopharma Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Clinipace Worldwide, Beckloff Associates, Inc., Kansas City Bioanalytical Laboratories
- Responsible party
- Sponsor
- Investigators
- Tim Freeman, Study director, Clinipace Worldwide
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01660633
- Sponsor's protocol ID
- CDX-353-002
- Status last verified
- Apr 2020
- First submitted
- 2 Aug 2012
- Last updated
- 21 Apr 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIb, Multicenter, Open-Label, Safety and Efficacy Study of High Dose Melphalan HCL for Injection (Propylene Glycol-Free)for Myeloablative Conditioning in Multiple Myeloma Patients Undergoing Autologous Transplantation
- ClinicalTrials.gov ID
- NCT01660633
- Acronym / sponsor ID
- CDX-353-002
- Conditions
- Multiple Myeloma
- Keywords
- Multiple Myeloma, High-Dose Melphalan, Propylene Glycol-Free, Autologous Stem Cell Transplantation, Captisol
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- Acrotech Biopharma Inc.Industry (pharma, biotech, devices)
- Collaborators
- Clinipace Worldwide, Beckloff Associates, Inc., Kansas City Bioanalytical Laboratories
- Study start
- Dec 2012
- Primary completion
- Feb 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 9 Aug 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this trial is to confirm the safety and efficacy of high-dose Melphalan HCL for Injection (Propylene Glycol-Free) as a myeloablative conditioning regimen in multiple myeloma patients (MM) undergoing autologous transplantation.
Detailed description
The sponsor of the current study is now Acrotech Biopharma, divested from Spectrum Pharmaceuticals Inc. (Spectrum), which licensed the Melphalan HC1 for Injection (Propylene Glycol-Free) product from Ligand Pharmaceuticals , formerly CyDex Pharmaceuticals, Inc. (CyDex). This new injectable form of melphalan HCL incorporates Captisol®, β cyclodextrin sulfobutyl ether sodium salts (also known as [SBE]7m-β-CD), into the product. Captisol is present to facilitate the use of an all aqueous diluent (normal saline) for reconstitution and administration of the freeze-dried product in place of the propylene glycol-ethanol diluent necessary for the currently used melphalan intravenous product. Captisol provides for solubilization and improved stability of the all aqueous reconstituted and diluted infusion solution.
This is the second of two studies supporting product registration. This study will be a multicenter study of high-dose Melphalan HCL for Injection (Propylene Glycol-Free) conducted in 60 patients who have symptomatic MM and qualify for autologous stem cell transplantation (ASCT).
During the Study Period, patients will receive 100mg/m2 of either Melphalan HCL for Injection (Propylene Glycol-Free) on Day -3 and on Day -2 for a total dose of 200mg/m2. Blood samples (5 timepoints post infusion) for population pharmacokinetic (PK) evaluation will be withdrawn through an indwelling i.v. cannula on the first day of administration of melphalan (Day -3) for all patients and then additional blood samples (2 timepoints post infusion) drawn in a subset of patients on the second day of melphalan administration (Day -2).
Following one day of rest after the high dose myeloablative conditioning (Day -1), patients will receive an autologous graft (Day 0).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| High-Dose Melphalan HCL for Injection (Propylene Glycol-Free) | Other | Drug: High-Dose Melphalan HCL for Injection (Propylene Glycol-Free), Other: Autologous TransplantationSubjects will receive only High-Dose Melphalan HCL for Injection (Propylene Glycol-free) at 200mg/m2 (100mg/m2/day for two days). |
Who may qualify
- Ages
- Up to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Patients with symptomatic MM based on IMWG guidelines requiring treatment who are eligible for ASCT.
- Patients who are 70 years of age or younger at time of transplant. Patients older than 70 years of age may be enrolled on a case-by-case basis if the patient meets local institutional criteria to receive a total melphalan dose of 200 mg/m2 as a conditioning regimen and if approved by the medical monitor.
- Patients with an adequate autologous graft, defined as an unmanipulated, cryopreserved, peripheral blood stem cell graft containing at least 2 × 106 CD34+ cells/kg based on patient body weight.
- Cardiac function: Left ventricular ejection fraction at rest >40% (documented within 8 weeks prior to Day -3).
- Hepatic function: Bilirubin <2 × the upper limit of normal and alanine aminotransferase (ALT)/aspartate aminotransferase (AST) <3 × upper limit of normal.
Key exclusion criteria (14 listed)
- Patients with smoldering MM not requiring therapy.
- Patients with plasma cell leukemia.
- Patients with systemic amyloid light chain amyloidosis.
- Patients with uncontrolled hypertension.
- Patients with an active bacterial, viral, or fungal infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High-Dose Melphalan HCL for Injection (Propylene Glycol-Free)Also: Evomela, Alkeran200 mg melphalan/m2 will be divided into two separate, consecutive doses of 100 mg/m2 administered on day -3 and day -2 prior to ASCT. The High-Dose Melphaln HCL for Injection (Propylene Glycol-Free) will be reconstituted to 5 mg/mL (also containing 270 mg/mL of Captisol®). The Melphalan HCL for Injection (Propylene Glycol Free) will be further diluted with normal saline to a concentration of no greater than 0.45 mg/mL and infused over 30 minutes ( + or - 3 minutes)via a central venous catheter. | Drug | High-Dose Melphalan HCL for Injection (Propylene Glycol-Free) |
| Autologous TransplantationAlso: Hematopoietic stem cell transplantationPatients who are myeloablative conditioning in multiple myeloma undergoing autologous transplantation( patients own blood-forming stem cells are collected to replace diseased bone marrow or bone marrow damaged by cancer treatment) | Other | High-Dose Melphalan HCL for Injection (Propylene Glycol-Free) |
Primary outcome
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time frame: Up to Day +100
AE coding will be performed using the MedDRA Version 11.0 or greater. The severity of the toxicities will be graded according to the NCI CTCAE Version 4.0 whenever possible. AEs occurring when treatment starts on Day -3 through Day + 100 will be recorded in the AE section of the eCRF and causality will be assigned by the Principal Investigator.
Mucositis Severity according to World Health Organization Scoring System
Time frame: Until Day +30
The baseline measurement will be the last assessment prior to receiving the first dose of study treatment. The on-treatment period will be defined as the day after the first dose of study treatment to 30 days after the last dose of study treatment. The incidence of severe mucositis (WHO Grade 3 or 4) will be summarized by frequencies and percentages. In addition, the incidence of oral mucositis will be summarized by WHO grade. Time from start of the first dose of study medication to peak oral mucositis score will also be calculated.
Mouth Pain Scores according to a Visual Analog Scale
Time frame: Until Day +30
Baseline VAS for mouth pain and dysphagia will be the VAS score collected prior to receiving the first dose of study medication. Analyses of changes and/or percent changes from baseline in the VAS scores will be analyzed for each time point collected during the 30 day on-treatment period. The minimum and maximum VAS scores during the 30 day on-treatment period will also be calculated for mouth pain and dysphagia, and the time to the minimum and maximum VAS scores will be summarized descriptively.
Treatment Related Mortality
Time frame: Up to Day +100
TRM, which is defined as death not due to disease progression before Day +90/+100, will be calculated. This outcome measure will be summarized by the cumulative incidence estimated with 95% confidence intervals.
5 secondary outcomes
MM response according to International Myeloma Working Group (IMWG) criteria.
Time frame: At the Day +100 visit
Myeloablation
Time frame: Up to Day +30
Neutrophil engraftment
Time frame: Up to Day +100
Platelet engraftment
Time frame: Up to Day +100
Non-engraftment
Time frame: Up to Day +100
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tim Freeman study director
Clinipace Worldwide
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing High-Dose Melphalan HCL for Injection (Propylene Glycol-Free) and Autologous Transplantation in people with Multiple Myeloma, run by Acrotech Biopharma Inc. at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Adverse Events as a Measure of Safety and Tolerability (time frame: Up to Day +100). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2020.