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

NCT00925782 | Completed Phase 2 Results DMC

• 1 other identifier: CDX-353-001
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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).

Conditions

Multiple Myeloma

Keywords

autologous stem cell transplantation

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Day -3 and Day -2

Secondary Outcomes (2)

• Determination of Myeloablation Following Melphalan-alkeran Sequence and Alkeran-melphalan Sequence Followed by ASCT

  30 days

• Determination of Engraftment Following Melphalan-alkeran Sequence and Alkeran-melphalan Sequence Followed by ASCT

  30 days

Study Arms (2)

Melphalan-Alkeran

OTHER

Subjects begin with treatment Melphalan and crossover to treatment Alkeran

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.

Drug: Melphalan HCL for Injection (Propylene Glycol-Free)/Alkeran for Injection; Drug: Alkeran for Injection/Melphalan HCL for Injection (Propylene Glycol-Free)

Interventions

Melphalan HCL for Injection (Propylene Glycol-Free)/Alkeran for Injection DRUG

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.

Also known as: Evomela

Alkeran-Melphalan; Melphalan-Alkeran

Alkeran for Injection/Melphalan HCL for Injection (Propylene Glycol-Free) DRUG

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.

Also known as: L-PAM, L-Sarcolysin

Alkeran-Melphalan; Melphalan-Alkeran

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Acrotech Biopharma Inc.: lead

Study Sites (1)

University of Kansas Medical Center/University of Kansas Cancer Center and Medical Pavillion

Kansas City, Kansas, 66160, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Melphalan; Injections

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)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Drug Administration Routes; Drug Therapy; Therapeutics

Results Point of Contact

• Title: Omar Aljitawi, M.D., Assistant Professor of Medicine
• Organization: University of Kansas Medical Center

oaljitawi@kumc.edu

913-588-6029

Study Officials

• Omar Aljitawi, MD

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2009
• First Posted: June 22, 2009
• Study Start: January 1, 2010
• Primary Completion: June 1, 2011
• Study Completion: July 1, 2011
• Last Updated: December 17, 2019
• Results First Posted: August 20, 2014

Record last verified: 2019-12

Locations

US (1)