Clinical trial NCT02518750 (phase 2, status: terminated)
Conditions: acute lymphoblastic leukemia, lymphoma, non-hodgkin's, leukemia, t-cell, leukemia, b-cell
ICD codes: C91.01, C91.02, C91.00, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, C91.61, C91.62, C91.51, C91.52, C91.60, C91.50, C91.31, C91.32, C91.A1, C91.A2, C91.11, C91.12, C91.30
Drugs: dexamethasone, panobinostat, liposomal vincristine, mitoxantrone, peg-asparaginase, bortezomib, intrathecal triples, high-dose methotrexate, 6-mercaptopurine, high-dose cytarabine, nelarabine, cyclophosphamide, etoposide, clofarabine
SMILES: C[C@@H](O[C@H]1OCCN(CC2=NNC(=O)N2)[C@H]1C1=CC=C(F)C=C1)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F, [H]\C(=C(\[H])C1=CC=C(CNCCC2=C(C)NC3=CC=CC=C23)C=C1)C(O)=NO, CC[C@]1(O)C[C@@H]2CN(C1)CCC1=C(NC3=CC=CC=C13)[C@@](C2)(C(=O)OC)C1=C(OC)C=C2N(C=O)[C@@H]3[C@]4(CCN5CC=C[C@](CC)([C@@H]45)[C@@H](OC(C)=O)[C@]3(O)C(=O)OC)C2=C1, OCCNCCNC1=CC=C(NCCNCCO)C2=C1C(=O)C1=C(C(O)=CC=C1O)C2=O, ClCCN(CCCl)P1(=O)NCCCO1, CN(CC1=CN=C2N=C(N)N=C(N)C2=N1)C1=CC=C(C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O, CN(CC1=CN=C2N=C(N)N=C(N)C2=N1)C1=CC=C(C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O, S=C1N=CNC2=C1NC=N2, NC1=NC(=O)N(C=C1)[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O, COC1=NC(N)=NC2=C1N=CN2[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O, ClCCN(CCCl)P1(=O)NCCCO1, OCCOCCN1CCN(CC1)C(C1=CC=CC=C1)C1=CC=C(Cl)C=C1, [H][C@@]12C[C@@H](C)[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)C=C[C@]12C
Reason stopped: 
    due to slow accrual
  
Eligibility criteria:

        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.