Multiple MyelomaPhase 2NCT00925782

PK Study of Melphalan HCL & Alkeran for Injection of MA Conditioning in MM Patients of Autologous Transplantation

A Phase 2 study testing Melphalan HCL for Injection (Propylene Glycol-Free)/Alkeran for Injection and Alkeran for Injection/Melphalan HCL for Injection (Propylene Glycol-Free) in people with Multiple Myeloma, run by Acrotech Biopharma Inc. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

To assess and compare the pharmacokinetics of Melphalan HCL for Injection (Propylene Glycol-Free) versus Alkeran for Injection in multiple myeloma (MM) patients undergoing autologous stem cell transplant (ASCT). Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Multiple Myeloma
What is being tested?: Melphalan HCL for Injection (Propylene Glycol-Free)/Alkeran for Injection and Alkeran for Injection/Melphalan HCL for Injection (Propylene Glycol-Free)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 24 participants
Where: 1 siteUnited States
Study dates: Jan 2010to Jul 2011
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients with symptomatic MM requiring treatment at diagnosis or anytime thereafter.
Patients with MM who qualify for ASCT therapy who have received appropriate primary induction therapy for transplantation.
Adult patients (≥ 18 years old) who are 70 years of age or younger at time of transplant; patients greater than 70 years of age may qualify 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 which is defined as an unmanipulated, cryopreserved, peripheral blood stem cell graft containing at least 2 × 106 CD34+ cells/kg based upon patient weight.
Patients with adequate organ function as measured by:
Cardiac: Left ventricular ejection fraction at rest >40% (documented within 12 weeks prior to Day -3).

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Hepatic: Bilirubin <2 × the upper limit of normal (ULN) and ALT/AST <3 × ULN.
Renal: Creatinine clearance >40 mL/minutes (measured or calculated/estimated).
Pulmonary: DLCO, FEV1, FVC >50% of predicted value (corrected for Hgb) or O2 saturation > 92% on room air (documented within 12 weeks prior to Day -3)

Who cannot join

Patients who have never advanced beyond Stage 1 MM since diagnosis.
Patients who have previously received more than one autologous stem cell transplant.
Patients with plasma cell leukemia.
Patients with MM and systemic AL amyloidosis.
ECOG performance status ≥2.
Patients with uncontrolled hypertension.

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Patients with an active bacterial, viral, or fungal infection.
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 (positive ß-HCG) or breastfeeding.
Female patients of childbearing potential who are unwilling to use adequate contraceptive techniques during and for 1 month following study treatment with Melphalan HCl for Injection (Propylene Glycol-Free).
Patients seropositive for 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 21 days prior to the ASCT, or planning to receive any of these treatments prior to study discharge.
Patients concurrently participating in any other clinical study.
Patients who are hypersensitive or intolerant to any component of the study drug formulation.

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Kansas Medical Center/University of Kansas Cancer Center and Medical Pavillion
Kansas City, Kansas, 66160

Other trials in United States

About this study

Official title: AA Phase IIA Open-Label, Randomized, PK Comparative, Cross-Over Study of Melphalan HCL for Injection (Propylene Glycol-Free) and Alkeran for Injection for Myeloablative Conditioning in MM Patients Undergoing Autologous Transplantation

Read the detailed description

This study will be a multicenter, open-label, randomized, comparative, cross-over study of high-dose Melphalan HCl for Injection (Propylene Glycol-Free) and Alkeran for Injection conducted in 24 patients who have symptomatic MM and qualify for ASCT.

During the Study Period, patients will be randomized to receive 100mg/m2 of either Melphalan HCl for Injection (Propylene Glycol-Free) or Alkeran for Injection on Day -3 and the alternate drug product on Day -2. Blood samples for pharmacokinetic (PK) evaluation will be withdrawn through an indwelling i.v. cannula each day of melphalan dosing (Day -3 and Day -2).

Following one day of rest after the myeloablative conditioning (Day -1), patients will receive an autologous graft.

Conditions: Multiple Myeloma
Being tested: Melphalan HCL for Injection (Propylene Glycol-Free)/Alkeran for Injection, Alkeran for Injection/Melphalan HCL for Injection (Propylene Glycol-Free)
Keywords: autologous stem cell transplantation
Medical subject headings: Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Melphalan HCL for Injection (Propylene Glycol-Free)/Alkeran for InjectionDrug
Also called Evomela
Patients will be randomized to receive 100 mg/m2 of Melphalan HCL for Injection (Propylene Glycol-Free) on Day -3 and Alkeran for Injection on Day -2 prior to ASCT.
Alkeran for Injection/Melphalan HCL for Injection (Propylene Glycol-Free)Drug
Also called L-PAM, L-Sarcolysin
Patients will be randomized to receive 100 mg/m2 of Alkeran for Injection on Day -3 and Melphalan HCL for Injection (Propylene Glycol-Free)on Day -2 prior to ASCT.

Study groups in NCT00925782
Study group	Role	What they receive
Melphalan-Alkeran	Other	Subjects begin with treatment Melphalan and crossover to treatment Alkeran Receives: Drug: Melphalan HCL for Injection (Propylene Glycol-Free)/Alkeran for Injection; Drug: Alkeran for Injection/Melphalan HCL for Injection (Propylene Glycol-Free)
Alkeran-Melphalan	Other	Subjects begin with treatment Alkeran and crossover to treatment Melphalan. Receives: Drug: Melphalan HCL for Injection (Propylene Glycol-Free)/Alkeran for Injection; Drug: Alkeran for Injection/Melphalan HCL for Injection (Propylene Glycol-Free)

What is being measured

The primary outcome is the main question the study is designed to answer.

Area Under the Curve (0-t)
AUC (0-t) was one of the pharmacokinetic endpoints to confirm pharmacokinetic similarity between Melphalan HCl for Injection (Propylene Glycol-Free) and Alkeran for Injection in patients with multiple myeloma. Pharmacokinetic similarity was defined as a difference of 20% or less in the 90% confidence intervals (CIs) for the ratios of the pharmacokinetic parameters (calculated using log-transformed data) for the two formulations.
The AUC results provided is the summary of Melphalan PK following Melphalan-Alkeran injection in Sequence 1 and Alkeran-melphalan injection in Sequence 2.
Measured: Day -3 and Day -2
Concentration-Max (Cmax)
Cmax was one of the pharmacokinetic endpoints to confirm pharmacokinetic similarity between Melphalan HCl for Injection (Propylene Glycol-Free) and Alkeran for Injection in patients with multiple myeloma. Pharmacokinetic similarity was defined as a difference of 20% or less in the 90% confidence intervals (CIs) for the ratios of the pharmacokinetic parameters (calculated using log-transformed data) for the two formulations.
The Cmax results provided is the summary of Melphalan PK following Melphalan-Alkeran injection in Sequence 1 and Alkeran-melphalan injection in Sequence 2.
Measured: Day -3 and Day -2

Secondary outcomes (2)

Determination of Myeloablation Following Melphalan-alkeran Sequence and Alkeran-melphalan Sequence Followed by ASCT
ANC <0.5 × 109/L, absolute lymphocyte count (ALC) <0.1 × 109/L, platelet count <20,000/mm3, or bleeding requiring transfusion. The first of 2 consecutive days for which cell counts drop below these cutoff levels was recorded as the date of myeloablation.
Since the two treatments were administered consecutively with 1 day rest, the time to myeloablation and myeloablation rate was measured after both treatments were administered.
Comparison of sequence effect was not planned in the study and due to small sample size, it was not performed.
Measured: 30 days
Determination of Engraftment Following Melphalan-alkeran Sequence and Alkeran-melphalan Sequence Followed by ASCT
Neutrophil engraftment was defined as the first day of 3 consecutive days where ANC (absolute neutrophil count) was higher than 500/ul. The two drug treatments in this cross-over design were administered on 2 subsequent days (Day -3 and Day -2). No per arm analysis was performed.
Since the two treatments were administered consecutively with 1 day rest, the time to engraftment and engraftment rate was measured after both treatments were administered.
Measured: 30 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2010Jul 2011

First posted22 Jun 2009 (estimated)
Study startJan 2010
Primary completionJun 2011
Study completionJul 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
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: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 24 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00925782
Sponsor's protocol ID: CDX-353-001
Status last verified: Dec 2019
First submitted: 18 Jun 2009
Last updated: 17 Dec 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Multiple Myeloma trials

Study at a glance

From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: AA Phase IIA Open-Label, Randomized, PK Comparative, Cross-Over Study of Melphalan HCL for Injection (Propylene Glycol-Free) and Alkeran for Injection for Myeloablative Conditioning in MM Patients Undergoing Autologous Transplantation
ClinicalTrials.gov ID: NCT00925782
Acronym / sponsor ID: CDX-353-001
Conditions: Multiple Myeloma
Keywords: autologous stem cell transplantation
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 24 participants (actual)
Lead sponsor: Acrotech Biopharma Inc.Industry (pharma, biotech, devices)
Study start: Jan 2010
Primary completion: Jun 2011 (actual)
Study completion: Jul 2011 (actual)
First posted: 22 Jun 2009 (estimated)
Results: Posted 20 Aug 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Following one day of rest after the myeloablative conditioning (Day -1), patients will receive an autologous graft.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Melphalan-Alkeran	Other	Drug: Melphalan HCL for Injection (Propylene Glycol-Free)/Alkeran for Injection, Drug: Alkeran for Injection/Melphalan HCL for Injection (Propylene Glycol-Free)Subjects begin with treatment Melphalan and crossover to treatment Alkeran
Alkeran-Melphalan	Other	Drug: Melphalan HCL for Injection (Propylene Glycol-Free)/Alkeran for Injection, Drug: Alkeran for Injection/Melphalan HCL for Injection (Propylene Glycol-Free)Subjects begin with treatment Alkeran and crossover to treatment Melphalan.

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

Patients with symptomatic MM requiring treatment at diagnosis or anytime thereafter.
Patients with MM who qualify for ASCT therapy who have received appropriate primary induction therapy for transplantation.
Adult patients (≥ 18 years old) who are 70 years of age or younger at time of transplant; patients greater than 70 years of age may qualify 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 which is defined as an unmanipulated, cryopreserved, peripheral blood stem cell graft containing at least 2 × 106 CD34+ cells/kg based upon patient weight.
Patients with adequate organ function as measured by:

Key exclusion criteria (15 listed)

Patients who have never advanced beyond Stage 1 MM since diagnosis.
Patients who have previously received more than one autologous stem cell transplant.
Patients with plasma cell leukemia.
Patients with MM and systemic AL amyloidosis.
ECOG performance status ≥2.

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
Melphalan HCL for Injection (Propylene Glycol-Free)/Alkeran for InjectionAlso: EvomelaPatients will be randomized to receive 100 mg/m2 of Melphalan HCL for Injection (Propylene Glycol-Free) on Day -3 and Alkeran for Injection on Day -2 prior to ASCT.	Drug	Alkeran-Melphalan, Melphalan-Alkeran
Alkeran for Injection/Melphalan HCL for Injection (Propylene Glycol-Free)Also: L-PAM, L-SarcolysinPatients will be randomized to receive 100 mg/m2 of Alkeran for Injection on Day -3 and Melphalan HCL for Injection (Propylene Glycol-Free)on Day -2 prior to ASCT.	Drug	Alkeran-Melphalan, Melphalan-Alkeran

Primary outcome

Area Under the Curve (0-t)
Time frame: Day -3 and Day -2
AUC (0-t) was one of the pharmacokinetic endpoints to confirm pharmacokinetic similarity between Melphalan HCl for Injection (Propylene Glycol-Free) and Alkeran for Injection in patients with multiple myeloma. Pharmacokinetic similarity was defined as a difference of 20% or less in the 90% confidence intervals (CIs) for the ratios of the pharmacokinetic parameters (calculated using log-transformed data) for the two formulations. The AUC results provided is the summary of Melphalan PK following Melphalan-Alkeran injection in Sequence 1 and Alkeran-melphalan injection in Sequence 2.
Concentration-Max (Cmax)
Time frame: Day -3 and Day -2
Cmax was one of the pharmacokinetic endpoints to confirm pharmacokinetic similarity between Melphalan HCl for Injection (Propylene Glycol-Free) and Alkeran for Injection in patients with multiple myeloma. Pharmacokinetic similarity was defined as a difference of 20% or less in the 90% confidence intervals (CIs) for the ratios of the pharmacokinetic parameters (calculated using log-transformed data) for the two formulations. The Cmax results provided is the summary of Melphalan PK following Melphalan-Alkeran injection in Sequence 1 and Alkeran-melphalan injection in Sequence 2.

2 secondary outcomes

Determination of Myeloablation Following Melphalan-alkeran Sequence and Alkeran-melphalan Sequence Followed by ASCT
Time frame: 30 days
Determination of Engraftment Following Melphalan-alkeran Sequence and Alkeran-melphalan Sequence Followed by ASCT
Time frame: 30 days

Results and safety

Results posted to the registry on 20 Aug 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Melphalan - Alkeran	12	12
Alkeran - Melphalan	12	12

Primary outcome: Area Under the Curve (0-t)

Time frame: Day -3 and Day -2. Geometric mean (Standard Deviation). Unit: min*ng/mL

Measure	Melphalan n = 24	Alkeran n = 24
Value	376577 (93401)	341183 (91349)

Population analysed: The pharmacokinetic-evaluable population was defined as all patients who completed dosing and adequate pharmacokinetic blood draws for the calculation of AUC and Cmax for both Melphalan HCl for Injection and Alkeran for Injection. The results are presented by each drug group that combines data from both sequence.

Primary outcome: Concentration-Max (Cmax)

Time frame: Day -3 and Day -2. Geometric mean (Standard Deviation). Unit: ng/mL

Measure	Melphalan n = 24	Alkeran n = 24
Value	4374 (1050)	3931 (1034)

Population analysed: The pharmacokinetic-evaluable population was defined as all patients who completed dosing and adequate subsequent pharmacokinetic blood draws for the calculation of area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax) for both Melphalan HCl for Injection and Alkeran for Injection.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Day -30 to 7 days post day of engraftment.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
All Study Participants	7 of 24 (29.2%)	24 of 24 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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.

Omar Aljitawi, MD principal investigator

University of Kansas Medical Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 15 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 17 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

Yes. Results are posted in the registry (first posted 20 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Area Under the Curve (0-t) (time frame: Day -3 and Day -2). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00925782.

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 17 Dec 2019.