To determine the activity of lenalidomide in the treatment of pediatric subjects with relapsed/refractory AML (with second or greater relapse or refractory to at least 2 prior induction attempts) measured by morphological complete response defined as either a CR or CRi within the first 4 cycles of treatment.
A Phase 2, Multicenter, Single-arm, Open-label Study to Evaluate the Activity, Safety and Pharmacokinetics of Lenalidomide (Revlimid®) in Pediatric Subjects From 1 to = 18 Years of Age With Relapsed or Refractory Acute Myeloid Leukemia.
This is a multicenter, open-label, single-arm, Phase 2, Simon's Optimal two-stage design study, with an Optional Extension Phase (OEP), that will assess the activity, safety and Pharmacokinetics (PK) of lenalidomide in pediatric subjects from 1 to ≤ 18 years of age with second or greater Relapsed or Refractory Acute Myeloid Leukemia (rrAML). A total of 43 evaluable subjects (18 subjects in Stage 1 and an additional 25 subjects in Stage 2) are required for assessment of the primary endpoint. To allow for subjects found to be unevaluable for the primary endpoint due to an incorrect diagnosis, not having a disease assessment post screening, or who discontinued prior to receiving lenalidomide, up to 4 additional subjects may be enrolled for a maximum of 47 evaluable subjects across approximately 70 sites. Approximately 50% of enrolled subjects will be younger than 12 years of age to provide adequate PK data for this age subset.
If during Stage 1, at least 3 of 18 subjects achieve a morphologic complete response (either CR or CRi) within the first 4 cycles of study treatment, then the study will proceed to Stage 2; otherwise, the study will be terminated. Similarly, if at the final analysis, at least 8 of 43 evaluable subjects across Stages 1 and 2 achieve a response (CR/CRi) within the first 4 cycles of study treatment, it will be concluded that lenalidomide has sufficient activity in pediatric Acute Myeloid Leukemia (AML) to warrant subsequent study.
The optional extension phase (OEP) will allow subjects who demonstrate clinical benefit, as assessed by the Investigator at the completion of 12 cycles of lenalidomide therapy, to continue receiving oral lenalidomide until they meet the criteria for study discontinuation. In the OEP, only safety, dosing, concomitant medications/procedures, and second primary malignancies (SPMs) will be monitored.
Leukemia, Myeloid Lenalidomide Revlimid Pediatric Relapsed or Refractory Acute Myeloid Leukemia Leukemia Thalidomide
Open to people ages 1 year to 18 years
Subjects must satisfy the following criteria to be enrolled in the study:
Donor lymphocyte infusion (DLI) is considered a reinduction attempt.
6 weeks if other bone marrow radiation has been administered.
If the subject has a history of maximum Grade 1 or 2 GVHD that was treated with systemic steroid (≥ 0.5 mg/kg/day prednisone equivalents) or other non-steroid systemic IST, the subject must be off all IST for at least 2 weeks, and must have ceased treatment doses of steroids for GVHD (≥ 0.5 mg/kg/day prednisone equivalents) for at least 4 weeks.
o If the subject has a history of Grade 3 or greater GVHD, the subject must be off all systemic IST for 4 weeks
o Topical therapy is permitted and does not imply the subject has active acute or chronic GVHD.
Physiologic dosing of hydrocortisone is permitted.
Creatinine clearance calculated using the Schwartz formula, or radioisotope glomerular filtration rate (GFR)> 70 mL/min/1.73 m2.
• Total bilirubin is ≤ 2 mg/dL unless the increase in bilirubin is attributable to Gilbert's Syndrome
• AST is ≤ 3.0 x upper normal limit (ULN) for age. For the purpose of this study, the ULN for AST is 50 U/L.
• ALT is ≤ 3.0 x upper normal limit (ULN) for age. For the purpose of this study, the ULN for ALT is 45 U/L.
NOTE: The pregnancy test 10 to 14 days prior to initiation of lenalidomide may be omitted,at the discretion of the investigator, for any FCCBP/FCBP who has high acuity disease requiring immediate treatment with lenalidomide. The pregnancy test within 24 hours prior to the first dose of lenalidomide is required to be performed.
The subject may not receive Investigational Product (IP) until the Investigator has verified that the results of these pregnancy tests performed on Cycle 1 Day 1 are negative. FCCBP/FCBP with regular or no menstrual cycles must agree to have pregnancy tests weekly for the first 28 days of study participation and then every 28 days while on study, at study Treatment Discontinuation Visit, and at Day 28 following IP discontinuation. If menstrual cycles are irregular, the pregnancy testing must occur weekly for the first 28 days and then every 14 days while on study, at study Treatment Discontinuation Visit, and at Days 14 and 28 following IP discontinuation.
All male and female subjects must follow all requirements defined in the Pregnancy Prevention Program.
The presence of any of the following will exclude a subject from enrollment:
We will not share your information with anyone other than the team in charge of this study. Submitting your contact information does not obligate you to participate in research.
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If you do not hear from the study team, please call 888-689-8273 and tell them you’re interested in study number NCT02538965.
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