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

• Status: Completed
• Trial end date: 2016-04-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a multicenter, open-label, dose escalation Phase 1 study.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Tragara Pharmaceuticals, Inc.
• Treatments: BB 1101; Citric Acid; Dexamethasone; Dexamethasone 21-phosphate; Dexamethasone acetate

Criteria

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