Re-Induction Therapy for Relapsed Pediatric T-Cell Acute Lymphoblastic Leukemia or Lymphoma

This is an interventional treatment trial for Acute Lymphoblastic Leukemia focused on measuring Hematopoietic Stem Cell Transplantation, Salvage Regimen, Re-Induction Therapy, Multi-agent chemotherapy Read More

Inclusion Criteria:

• Participants must have relapsed or refractory acute lymphoblastic leukemia or lymphoma (ALL):

  • Stratum I: T-cell lymphoblastic leukemia or lymphoma in first relapse or refractory to one or two courses of frontline induction therapy.
  • Stratum II: B-cell or T-cell lymphoblastic leukemia or lymphoma in second or third relapse or refractory to 2 or 3 induction or re-induction attempts. Patients with Ph+ ALL must be refractory or relapsed after treatment with regimen that included a tyrosine kinase inhibitor (TKI).

• Relapse in ALL is defined as the reappearance (in a patient who has previously achieved remission) of leukemic blasts in the bone marrow.

  • Should flow cytometric analyses suggest relapse (by the reappearance of a similar immunophenotype to the original leukemia) in the presence of <5% blasts morphologically, a repeat bone marrow test is recommended to confirm relapse.
  • Molecular or genetic relapse is characterized by the reappearance of a cytogenetic or molecular abnormality.
• Age is ≤ 21 years (participant has not yet reached 22nd birthday).
• Able to swallow capsules.
• Karnofsky or Lansky performance score is ≥ 60%. The Lansky performance score should be used for participants < 16 years and the Karnofsky performance score for participants ≥ 16 years.

• Prior therapy:

  • There is no waiting period for participants who relapse while receiving therapy if they are free from side effects attributable to such therapy.
  • Emergent radiation therapy, one dose of intrathecal chemotherapy and up to 7 days of steroids or hydroxyurea are permitted before start of treatment in participants who relapse after completion of frontline therapy. Other circumstances must be cleared by PI or medical designee.
  • At least 90 days have elapsed since bone marrow transplant and participant is off immune suppression for ≥ 2 weeks, if applicable.

• Adequate renal function defined as glomerular filtration rate ≥ 60 cc/min/1.73m^2 or serum creatinine based on age as follows:

  • If age is 1 to 2 years, then maximum serum creatinine (mg/dL) is 0.6 for males or females.
  • If age is 2 to 6 years, then maximum serum creatinine (mg/dL) is 0.8 for males or females.
  • If age is 6 to 10 years, then maximum serum creatinine (mg/dL) is 1 for males or females.
  • If age is 10 to <13 years, then maximum serum creatinine (mg/dL) is 1.2 for males or females.
  • If age is 13 to 16 years, then maximum serum creatinine (mg/dl) is 1.5 for males or 1.4 for females.
  • If age is > 16 years, then maximum serum creatinine (mg/dl) is 1.7 for males or 1.4 for females.

• Adequate hepatic function defined as:

  • Direct bilirubin ≤ 1.4 mg/dL (if total bilirubin > 1.4 mg/dL) AND
  • AST and ALT < 5 x ULN for age.
• Adequate cardiac function defined as shortening fraction of ≥ 27% or ejection fraction ≥ 45%.

• Lymphoma participants without bone marrow involvement must have:

  • Absolute neutrophil count (ANC) >1,000/mm3, AND
  • Platelet count ≥50,000/mm^3 (without transfusion support)
  • NOTE: These criteria are waived for participants with leukemia or lymphoma participants with bone marrow involvement.
• Written, informed consent and assent following Institutional Review Board, NCI, FDA and OHRP guidelines.

Exclusion Criteria:

• Prior histone deacytylases (HDAC), DAC, HSP90 inhibitors or valproic acid for treatment of cancer.
• Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment.
• Impaired cardiac function or clinically significant cardiac diseases, history of arrhythmia (including ventricular fibrillation or torsade de pointes), bradycardia <50 bpm, screening ECG with prolonged QTc or uncontrolled hypertension.
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat.
• Patients with diarrhea > CTCAE grade 2.
• Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes or active or uncontrolled infection) including abnormal laboratory values, that could cause unacceptable safety risks or compromise compliance with the protocol.
• Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting treatment.
• Patients who have received targeted agents within 2 weeks or within 5 half-lives of the agent and active metabolites (whichever is longer) and who have not recovered from side effects of those therapies.
• Patients who have undergone major surgery ≤ 4 weeks prior to starting treatment or who have not recovered from side effects of such therapy.
• Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis B/C.
• Inability to swallow capsules.
• Active, uncontrolled infection or severe concurrent medical disease, including but not limited to congestive heart failure, cardiac arrhythmias, or psychiatric illness.
• Isolated extramedullary relapse (leukemia) or isolated CNS lymphoma.
• Pregnant or lactating (female participant of childbearing potential must have negative serum or urine pregnancy test required within 7 days prior to start of treatment). Male or female of reproductive potential has agreed to use effective contraception method for duration of study treatment.
• Down syndrome.
• Inability or unwillingness or research participant or legal guardian/representative to give written informed consent.