Phase 1 Study of TG02 Citrate in Patients With Advanced Hematological Malignancies

Part 1 Inclusion Criteria: * Relapsed AML, ALL, CML in blast crisis, or MDS * 65+ yrs with AML not eligible for standard frontline chemo * Interval from prior treatment to time of study drug at least 5 half-lives for cytotoxic/ noncytotoxic agents. * Persistent clinically significant toxicities from prior chemo ≤ Grd 1 * ECOG PS 0-2 * Lab values: * Cr ≤ 2X ULN * ALT and/or AST ≤2.5 X ULN * Total bilirubin ≤1.5 X ULN unless considered due to Gilbert's syndrome * Negative pregnancy test * Can take oral med Part 2 Inclusion Criteria: * Relapsed multiple myeloma. At least ≥1 line of therapy and progressed after ≥1 prior therapy * Measurable disease defined as at least one of the following: * Serum M ≥500 mg/dL * Urine M ≥200 mg per 24hr * Involved FLC ≥10 mg/dL and abnormal FLC ratio in serum (\<0.26 or \>1.65) * Measurable soft tissue plasmacytoma * Persistent clinically significant toxicities from prior chemo ≤ Grd 1 * ECOG PS 0-2 * Lab values: * ANC of \>1000/mm3 * Platelets ≥50,000/mm3 * Cr ≤2X the ULN * ALT and/or AST ≤2.5X ULN * Total bilirubin ≤1.5X ULN, unless considered due to Gilbert's syndrome * Negative pregnancy test * Can take oral med Part 3 Inclusion Criteria: * Measurable disease defined as at least one of the following: * Serum M ≥500 mg/dL * Urine M protein ≥200 mg per 24hr * Involved FLC level ≥10 mg/dL and abnormal FLC ratio in serum (\<0.26 or \>1.65) * Meet at least one of the criteria below: * a. ≥2 prior therapies including proteasome inhibitor and immunomodulatory agent (IMiD) * b. ≥1 prior therapy and one of the following abnormalities: 17p del, p53, 1q amp, 1p del, t(4;14) * Interval from prior treatment to time of study drug at least 5 half-lives or 3 wks, which ever is shorter, for noncytotoxic agents * Persistent clinically significant toxicities from prior chemo ≤ Grd 1 or Grd 2 neuropathy without pain * ECOG PS 0-2 * Lab values: * ANC of \>1000/mm3 independent of G-CSF * Platelets ≥50,000/mm3 independent of transfusion * MDRD calculated or measured CrCl of ≥30 mL/min * ALT and/or AST ≤3X ULN * Total bilirubin ≤2X ULN, unless considered due to Gilbert's syndrome * Negative pregnancy test * Can take oral med Part 4 Inclusion Criteria: * Measurable disease defined as at least one of the following: * Serum M ≥500 mg/dL * Urine M protein ≥200 mg per 24hr * Involved FLC level ≥10 mg/dL and an abnormal FLC ratio in serum (\<0.26 or \>1.65) * Received prior therapies including: * a. bortezomib * b. an IMiD * c. carfilzomib. Demonstrated disease progression on or within 60d of completion of carfilzomib therapy * Interval from prior treatment to time of study drug at least 5 half-lives or 3 wks, which ever is shorter, for noncytotoxic agents. * Persistent clinically significant toxicities from prior chemo ≤ Grd 1, or Grd 2 neuropathy without pain. * ECOG PS 0-2 * Lab values: * ANC of \>1000/mm3 independent of G-CSF * Platelets ≥50,000/mm3 independent of transfusion * MDRD calculated or measured CrCl of ≥30 mL/min * ALT and/or AST ≤3X ULN * Total bilirubin ≤2X ULN, unless considered due to Gilbert's syndrome * Negative pregnancy test * Can take oral med Parts 1 and 2 Exclusion Criteria: * Previous allogenic hematopoietic transplant within 90 d * Concurrent severe or uncontrolled medical disease that would compromise the safety or compromise the ability of the patient to complete the study * Prolonged QTC interval \>450ms * Symptomatic CNS metastases * Known HIV or AIDS * Actively treated for a second malignancy * Pregnant or nursing women Part 3 Exclusion Criteria: * Multiple myeloma of IgM subtype, POEMS, plasma cell leukemia * Corticosteroids discontinued ≥7 days of initiating therapy * Previous chemo within 2 wks * Hx of ventricular arrhythmia or symptomatic conduction abnormality within 12m * CHF, symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, myocardial infarction within 6m * Prolonged QTc interval (males \>450ms, females \>470ms) * Previous allogeneic hematopoietic transplant within 90 days of study enrollment, Active GVHD requiring treatment. * Concurrent severe or uncontrolled medical disease that would compromise the safety or compromise the ability of the patient to complete the study * Symptomatic CNS metastases * Known HIV or AIDS * Prior or 2nd malignancy, except non-melanoma skin cancer, completely resected cervical or prostate cancer (with PSA of less than or equal to 0.1 ng/ml), or other cancer for which the subject has received curative therapy at least 3 yrs prior to study entry * Treatment-related MDS * Significant neuropathy (Grd 3-4 or Grd 2 with pain) at the time of 1st dose * Primary AL amyloidosis * Pleural effusions requiring thoracentesis or ascites requiring paracentesis * Pregnant or nursing women Part 4 Exclusion Criteria: * Multiple myeloma of IgM subtype, POEMS, plasma cell leukemia * Previous chemo within 2 wks * Hx ventricular arrhythmia or symptomatic conduction abnormality within 12m * CHF, symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, and myocardial infarction within 6m * Prolonged QTc interval (males \>450ms, females \>470ms) * Previous allogeneic hematopoietic transplant within 90 days. Active GVHD requiring treatment * Concurrent severe or uncontrolled medical disease that would compromise the safety or compromise the ability of the patient to complete study * Symptomatic CNS metastases * Known HIV or AIDS * Prior or 2nd malignancy, except non-melanoma skin cancer, completely resected cervical or prostate cancer (with PSA of less than or equal to 0.1 ng/ml), or other cancer for which the subject has received curative therapy at least 3 yrs prior to study entry * Treatment-related MDS * Significant neuropathy (Grd 3-4 or Grd 2 with pain) at the time of 1st dose * Primary AL amyloidosis * Pleural effusions requiring thoracentesis or ascites requiring paracentesis * Pregnant or nursing women