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- Klinische proef NCT01204164
Phase 1 Study of TG02 Citrate in Patients With Advanced Hematological Malignancies (TG02-101)
Phase 1 Dose-Escalation and Pharmacokinetic Study of TG02 Citrate in Patients With Advanced Hematological Malignancies
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
This is a multicenter, open-label, dose escalation, Phase 1/1b study.
For Parts 1, 2, and 3 of the study, the primary objective is to determine the highest dose of TG02 citrate that can safely be given to patients with different types of hematological malignancy.
For Part 4, the primary objective is to evaluate the safety and tolerability of once-weekly dosing at the maximum-tolerated dose/ Recommended Phase 2 Dose of TG02 in combination with carfilzomib.
This study consists of four parts:
- Part 1: single agent TG02 in acute leukemia patients
- Part 2: single agent TG02 in multiple myeloma patients
- Part 3: TG02 in combination with carfilzomib in multiple myeloma patients
- Part 4: TG02 in combination with carfilzomib in carfilzomib refractory multiple myeloma patients.
Studietype
Inschrijving (Verwacht)
Fase
- Fase 1
Contacten en locaties
Studie Locaties
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Colorado
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Denver, Colorado, Verenigde Staten, 80218
- RMCC
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Georgia
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Atlanta, Georgia, Verenigde Staten, 30322
- Emory
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Illinois
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Chicago, Illinois, Verenigde Staten, 60612
- Rush
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Indiana
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Indianapolis, Indiana, Verenigde Staten, 46202
- IU
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New Jersey
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Hackensack, New Jersey, Verenigde Staten, 07601
- HUMC
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New York
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New York City, New York, Verenigde Staten, 10021
- Cornell
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Ohio
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Columbus, Ohio, Verenigde Staten, 43210
- OSU
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Tennessee
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Nashville, Tennessee, Verenigde Staten, 37203
- SCRI
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Texas
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Houston, Texas, Verenigde Staten, 77030
- MDACC
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Niet-gerandomiseerd
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: TG02 in AL
Single agent TG02 citrate in acute leukemia patients
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TG02 citrate capsules given orally.
Andere namen:
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Experimenteel: TG02 in MM
Single Agent TG02 citrate in multiple myeloma patients
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TG02 citrate capsules given orally.
Andere namen:
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Experimenteel: TG02 + CFZ in MM
TG02 in combination with carfilzomib and dexamethasone in multiple myeloma patients
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TG02 citrate capsules given orally.
Andere namen:
Carfilzomib per PI
Andere namen:
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Experimenteel: TG02 + CFZ + DEX in CFZ refractory MM
TG02 in combination with carfilzomib and dexamethasone in carfilzomib refractory multiple myeloma patients
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TG02 citrate capsules given orally.
Andere namen:
Carfilzomib per PI
Andere namen:
Dexamethasone (Oral or IV)
Andere namen:
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Maximum Tolerated Dose
Tijdsspanne: 28 days
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Maximum Tolerated Dose refers to the highest dose of TG02 administered that will produce the desired effect without unacceptable toxicity.
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28 days
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
---|---|---|
Safety
Tijdsspanne: 28 days
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Safety data will include vital signs, ECGs, PE findings, clinical laboratory parameters, ECOG PS, AEs/SAEs and concomitant medications.
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28 days
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Pharmacokinetics of TG02
Tijdsspanne: 28 days
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Plasma will be analyzed to determine TG02 concentration.
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28 days
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Clinical Benefit Response
Tijdsspanne: 28 days
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Clinical Benefit Response is defined as the sum of all response categories for Overall Response Rate (ORR is defined as the sum of patients with sCR, CR, VGPR and PR) plus minimal response (MR).
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28 days
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Overall Response Rate
Tijdsspanne: 28 days
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Overall Response Rate is defined as the sum of patients with sCR, CR, VGPR and PR.
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28 days
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Progression-Free Survival
Tijdsspanne: 28 days
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Progression-Free Survival is the time to disease progression or death, which is measured from the date of first study drug administration until the first date that recurrent or progressive disease is objectively documented or the date of death.
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28 days
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Overall Survival
Tijdsspanne: 28 days
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Overall Survival is time to death, which is measured from the date of first study drug administration until the date of death.
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28 days
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Duration of Response
Tijdsspanne: 28 days
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Duration of Response is the duration from first observation of response to the first documentation of disease progression, with deaths from causes other than disease progression censored.
For the purposes of the calculation of the DOR, the date at which the response status was first observed rather than the date of confirmation is used as the start date.
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28 days
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Pharmacodynamics
Tijdsspanne: 28 days
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Pharmacodynamic sampling may include whole blood and bone marrow at baseline and post-treatment for pathway determination if available.
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28 days
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Medewerkers en onderzoekers
Sponsor
Onderzoekers
- Studie directeur: T Parrott, Tragara Pharmaceuticals
Studie record data
Bestudeer belangrijke data
Studie start
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
Laatste update geplaatst (Schatting)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
- Pathologische processen
- Hart-en vaatziekten
- Vaatziekten
- Ziekten van het immuunsysteem
- Neoplasmata per histologisch type
- Neoplasmata
- Lymfoproliferatieve aandoeningen
- Immunoproliferatieve aandoeningen
- Neoplasmata per site
- Beenmergziekten
- Hematologische ziekten
- Hemorragische aandoeningen
- Myeloproliferatieve aandoeningen
- Hemostatische aandoeningen
- Paraproteïnemieën
- Bloed eiwit stoornissen
- Neoplastische processen
- Neoplasmata, plasmacel
- Leukemie
- Celtransformatie, neoplastisch
- Kankerverwekkendheid
- Leukemie, myeloïde
- Leukemie, Myelogeen, Chronisch, BCR-ABL Positief
- Hematologische neoplasmata
- Multipel myeloom
- Ontploffingscrisis
- Fysiologische effecten van medicijnen
- Autonome agenten
- Agenten van het perifere zenuwstelsel
- Ontstekingsremmende middelen
- Antineoplastische middelen
- Anti-emetica
- Gastro-intestinale middelen
- Glucocorticoïden
- Hormonen
- Hormonen, hormoonvervangers en hormoonantagonisten
- Antineoplastische middelen, hormonaal
- Dexamethason
Andere studie-ID-nummers
- TG02-101
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .
Klinische onderzoeken op Multipel myeloom
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University of ArkansasVoltooidMEERDERE MYELOMAVerenigde Staten
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PETHEMA FoundationGlaxoSmithKlineWervingTERUGVALLEN EN/OF REFRACTAIRE MEERDERE MYELOMASpanje
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Mario BoccadoroActief, niet wervend
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Beth Israel Deaconess Medical CenterAmgenVoltooidAML | MDS | CLL | ALLE | CML Chronic Phase, Accelerated Phase, or Blast Crisis | RELAPSED NON-HODGKIN'S OR HODGKIN'S LYMPHOMA | APLASTIC ANEMIA | MEERDERE MYELOMA | MYELOPROLIFERATIVE DISORDER (P Vera, CMML, ET)
Klinische onderzoeken op TG02 citrate
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National Cancer Institute (NCI)VoltooidGlioblastoom | Astrocytoom | Hersentumor | Gliosarcoom | AstroglioomVerenigde Staten
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Lee's Pharmaceutical LimitedChina Oncology Focus LimitedIngetrokkenHepatocellulair carcinoom
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Lee's Pharmaceutical LimitedOnbekend
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Targovax ASABeëindigd
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Tragara Pharmaceuticals, Inc.VoltooidChronische lymfatische leukemie | Klein lymfocytisch lymfoomVerenigde Staten
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European Organisation for Research and Treatment...Tragara Pharmaceuticals, Inc.VoltooidGlioblastoom | Astrocytoom, graad IIIFrankrijk, Oostenrijk, Duitsland, Nederland, Zwitserland