Clinical trial NCT00925782: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: autologous stem cell transplantation
Lead sponsor: Acrotech Biopharma Inc.
Sponsor class: INDUSTRY
First posted: 2009-06-22
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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 Blood samples for pharmacokinetic (PK) evaluation will be withdrawn through an indwelling i.v. cannula each day of melphalan dosing (Day -3 and Day -2).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.

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.

Primary outcomes:
measure: Area Under the Curve (0-t)
timeFrame: Day -3 and Day -2
measure: Concentration-Max (Cmax)
timeFrame: Day -3 and Day -2
Secondary outcomes:
measure: Determination of Myeloablation Following Melphalan-alkeran Sequence and Alkeran-melphalan Sequence Followed by ASCT
timeFrame: 30 days
measure: Determination of Engraftment Following Melphalan-alkeran Sequence and Alkeran-melphalan Sequence Followed by ASCT
timeFrame: 30 days
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: University of Kansas Medical Center/University of Kansas Cancer Center and Medical Pavillion
state: Kansas
Study officials:
affiliation: University of Kansas Medical Center
name: Omar Aljitawi, MD
role: PRINCIPAL_INVESTIGATOR
References: