A Phase 1 Dose-escalation Study to Evaluate the Safety and Pharmacokinetics (PK) of Palifermin in Subjects With Acute Leukemias Undergoing HSCT

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• Leukemia 5,441

Keywords

• Oral Mucositis
• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Palifermin
• Kepivance

Leukemia

5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.

This study's enrollment of 27 is below the median of 38 across 4,247 interventional studies indexed under Leukemia.

Lead sponsor

Swedish Orphan Biovitrum is the lead sponsor of 78 studies on the registry; 4 are open to participants now.

Of its 17 completed or terminated interventional studies of FDA-regulated products, 15 (88%) have results posted.

Study arms

• Experimental
  Palifermin Dose Escalation

  A 3 dose escalation design. Sucessive cohorts of patient (9 patients per group) will each be administered Palifermin as an IV bolus injection (40, 60 or 80 µg) once daily for 3 consecutive days before the start of conditioning regimen (chemotherapy and total body irradiation) and after HCST (Day -10, -9, -8 and Day 0, +1, +2 respectively).

  Drug: Palifermin · Radiation: Total Body irradiation · Drug: Chemotherapy

Interventions

• DrugPalifermin

  Palifermin will be administered as an IV bolus injection (40, 60 or 80 µg/kg/day)once daily for 3 consecutive days before the start of conditioning regimen and after HCST (Day -10, -9, -8 and Day 0, +1, +2 respectively).

  Also known as: Kepivance

• RadiationTotal Body irradiation
• DrugChemotherapy

  High dose etoposide, Cyclophosphamide

Primary outcomes

1. Incidence of Dose Limiting Toxicities (DLTs)

   A DLT is appearance of side effects during treatment severe enough to prevent further increase in dosage or strength of treatment agent, or to prevent continuation of treatment at any dosage level. A DLT was defined as: Grade 3 or 4 AE \[based on Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE) v3.0\] considered by the investigator to be related to palifermin with the exceptions: Grade 3 erythema, pruritus or rash that resolves within 7 days of the last dose of palifermin. The percentage of particiapnts with a DLT during the study was assessed.

   Time frame: Approximately 1 month duration (Day -10 through Day +16)

Secondary outcomes

1. Incidence of Serum Palifermin Antibody Formation

   The percentage of participants developing palifermin antibodies during the study was assessed.

   Time frame: Approximately 4 month duration (Through Day + 100 (+/- 40 days))

2. Incidence of Severe Adverse Events (AEs)

   The percentage of participants with a severe AE during the study was assessed.

   Time frame: Approximately 1 1/2 months duration (Through Day +30/End of Treatment)

3. Incidence of Laboratory Abnormalities

   The percentage of participants with a laboratory value outside the normal ranges during the study.

   Time frame: Approximately 1 1/2 months duration (Through Day +30/End of Treatment)

4. Pharmacokinetics of Palifermin, Clearence (CL) After the 1st Intravenous (IV) Bolus Injection for Multiple Dose Levels

   Clearence was estimated as dose divided by the area under serum concentration-time curve from time zero to infinity where the dose was given in amount palifermin actually administered.

   Time frame: Day -10

5. Pharmacokinetics of Palifermin, Volume of Distribution at Steady State (Vss) After the 1st IV Bolus Injection for Multiple Dose Levels

   Time frame: Day -10

6. Pharmacokinetics of Palifermin, Terminal Half-life (t½,z) After the 1st IV Bolus Injection for Multiple Dose Levels

   The terminal half-life was calculated as ln(2)/lambda,z where lambda,z was estimated using at least three quantifiable serum concentrations of the terminal log-linear phase.

   Time frame: Day -10

7. Pharmacokinetics of Palifermin, t½,z After the 3rd IV Bolus Injection for Multiple Dose Levels

   The terminal half-life was calculated as ln(2)/lambda,z where lambda,z was estimated using at least three quantifiable serum concentrations of the terminal log-linear phase.

   Time frame: Day -8

8. Pharmacokinetics of Palifermin, Area Under the Concentration Time Curve From Zero to the End of the Dosing Interval (AUCtau) After the 1st IV Bolus Injection for Multiple Dose Levels

   The AUC was estimated using the linear/log trapezoidal method for AUC0-tau from time zero to the end of the dosing interval (24 hours (hrs) post-dose) Data collected at time points: 0, 2 minutes (min), 15 min, 30 min, 60 min, 2 hrs, 4 hrs, 6, hrs, 10, hrs and 24 hrs post-dose.

   Time frame: Day -10

9. Pharmacokinetics of Palifermin, AUCtau After the 3rd IV Bolus Injection for Multiple Dose Levels

   The AUC was estimated using the linear/log trapezoidal method for AUC0-tau from time zero to the end of the dosing interval (24 hours (hrs) post-dose) Data collected at time points: 0, 2 minutes (min), 15 min, 30 min, 60 min, 2 hrs, 4 hrs, 6, hrs, 10, hrs and 24 hrs post-dose.

   Time frame: Day -8

10. Long-Term Follow-Up: Incidence of Secondary Malignancies

    Time frame: Up to 4 years duration (Assessments performed on months 6, 9, 12 (+/- 30 Days) for the first year and then annually)

11. Long-Term Follow-Up: Progression Free Survival

    Progression free survival (PFS) was defined as the number of days between the date of first investigational product administration and the date when physical or radiological evidence of disease progression is determined or death (regardless of cause)

    Time frame: Up to 4 years duration (Assessments performed on months 6, 9, 12 (+/- 30 Days) for the first year and then annually)

12. Long-Term Follow-Up: Overall Survival

    Overall survival was defined as the number of days from the date of first investigational product administration to the date of death (regardless of cause)

    Time frame: Up to 4 years duration (Assessments performed on months 6, 9, 12 (+/- 30 Days) for the first year and then annually)

Baseline characteristics