Back to resultsPK Study of Melphalan HCL & Alkeran for Injection of MA Conditioning in MM Patients of Autologous Transplantation
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Melphalan HCL for Injection (Propylene Glycol-Free)/Alkeran for Injection
Alkeran for Injection/Melphalan HCL for Injection (Propylene Glycol-Free)
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring autologous stem cell transplantation
Eligibility Criteria
Inclusion Criteria:
- 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).
- 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)
Exclusion Criteria:
- 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.
- 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.
Sites / Locations
- University of Kansas Medical Center/University of Kansas Cancer Center and Medical Pavillion
Arms of the Study
Arm 1
Arm 2
Arm Type
Other
Other
Arm Label
Melphalan-Alkeran
Alkeran-Melphalan
Arm Description
Subjects begin with treatment Melphalan and crossover to treatment Alkeran
Subjects begin with treatment Alkeran and crossover to treatment Melphalan.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
Full Information
NCT ID
NCT00925782
First Posted
June 18, 2009
Last Updated
December 9, 2019
Sponsor
Acrotech Biopharma Inc.
1. Study Identification
Unique Protocol Identification Number
NCT00925782
Brief Title
PK Study of Melphalan HCL & Alkeran for Injection of MA Conditioning in MM Patients of Autologous Transplantation
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
Study Type
Interventional
2. Study Status
Record Verification Date
December 2019
Overall Recruitment Status
Completed
Study Start Date
January 2010 (undefined)
Primary Completion Date
June 2011 (Actual)
Study Completion Date
July 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Acrotech Biopharma Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
autologous stem cell transplantation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Melphalan-Alkeran
Arm Type
Other
Arm Description
Subjects begin with treatment Melphalan and crossover to treatment Alkeran
Arm Title
Alkeran-Melphalan
Arm Type
Other
Arm Description
Subjects begin with treatment Alkeran and crossover to treatment Melphalan.
Intervention Type
Drug
Intervention Name(s)
Melphalan HCL for Injection (Propylene Glycol-Free)/Alkeran for Injection
Other Intervention Name(s)
Evomela
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Alkeran for Injection/Melphalan HCL for Injection (Propylene Glycol-Free)
Other Intervention Name(s)
L-PAM, L-Sarcolysin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Area Under the Curve (0-t)
Description
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.
Time Frame
Day -3 and Day -2
Title
Concentration-Max (Cmax)
Description
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.
Time Frame
Day -3 and Day -2
Secondary Outcome Measure Information:
Title
Determination of Myeloablation Following Melphalan-alkeran Sequence and Alkeran-melphalan Sequence Followed by ASCT
Description
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.
Time Frame
30 days
Title
Determination of Engraftment Following Melphalan-alkeran Sequence and Alkeran-melphalan Sequence Followed by ASCT
Description
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.
Time Frame
30 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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).
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)
Exclusion Criteria:
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.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Omar Aljitawi, MD
Organizational Affiliation
University of Kansas Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Kansas Medical Center/University of Kansas Cancer Center and Medical Pavillion
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
12. IPD Sharing Statement
Learn more about this trial
PK Study of Melphalan HCL & Alkeran for Injection of MA Conditioning in MM Patients of Autologous Transplantation
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