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Study of ABT-888 in Combination With Bortezomib and Dexamethasone in Patients With Relapsed Refractory Myeloma

21. september 2017 opdateret af: AHS Cancer Control Alberta

Phase I Study of ABT-888 in Combination With Bortezomib and Dexamethasone in Patients With Relapsed Refractory Myeloma

The combination of PARP inhibitor (ABT-888) with a proteasome inhibitors (bortezomib) have demonstrated significant anti-myeloma effects in preclinical lab and animal studies. The goal of this phase I trial is to evaluate in patients with relapsed or refractory multiple myeloma the safety, toxicity profile and tolerability of ABT-888 (Veliparib) administered on a schedule including twice daily oral dosing for 14 days followed by 1 week rest in combination with standard dosing of Bortezomib.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

This is a dose-finding / dose escalation phase I trial of ABT-888 (Veliparib) in combination with Bortezomib and Dexamethasone in patients with relapsed or refractory multiple myeloma. ABT-888 is given orally (PO) twice daily (every 12 hours) for 14 days in a 21 days cycle.

First dose to be given within 1 hour of Bortezomib on day 1. Planned starting dose is 20 mg PO every 12 hours. Starting dose escalation is planned until an MTD is reached.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

19

Fase

  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Tom Baker Cancer Centre

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  • Confirmed diagnosis of multiple myeloma.
  • Measurable disease, according to the International Myeloma Working Group criteria.
  • ECOG performance status 0, 1 or 2.
  • Patients must have received prior treatment for MM and have relapsed or progressed on prior therapy; no limit on number of prior treatment regimens, but prior treatment must be completed 2 weeks prior to registration. Prior exposure to Bortezomib is not an exclusion criteria as long as patients did not progress or relapse while receiving or within 3 months of completing trt with bortezomib
  • Prior radiation, completed at least 4 weeks prior to registration, is permitted.
  • Adequate marrow reserve, liver and renal function

Exclusion Criteria:

  • patients with a history of other malignancies, except: adequately treated nonmelanoma skin cancer, curatively treated in-situ cancer of the cervix, prostate cancer with stable PSA for > 3 years, or other solid tumours curatively treated with no evidence of disease for > 5 years.
  • Patients with preexisting grade 2 (or higher) sensory neuropathy or grade 1 sensory neuropathy with neuropathic pain.
  • Pregnant or lactating women
  • Patients receiving concurrent treatment with other anti-cancer therapy any other investigational agents.
  • Active or uncontrolled infections
  • Patient with known documented congenital or acquired risk factor for thromboembolic event
  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: ABT-888/Bortezomib
Patients will be on a treatment schedule including twice daily oral dosing for 14 days followed by 1 week rest in combination with standard dosing of Bortezomib and Dexamethasone in a 21 days cycle for a total of 14 cycles.
Medicin: ABT-888/Bortezomib
ABT-888 is given orally (PO) twice daily (every 12 hours) for 14 days in a 21 days cycle. First dose to be given within 1 hour of Bortezomib on day 1. Planned starting dose is 20 mg PO every 12 hours. Starting dose escalation is planned until an MTD is reached.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Determine the maximum tolerated dose (MTD) of ABT-888.
Tidsramme: 21 Day Cycle
Study follows a modified dose escalation scheme with a 3+3 design (3 to 6 patients per dose level or cohort). Only the ABT-888 dose will be escalated with a maximum dose of ABT-888 of 100 mg PO BID. If >1 out 6 patients at any dose level suffer dose limiting toxicity, then dose escalation is stopped, and this dose is declared as MTD. 3 additional patients will be entered at the next lowest dose level. The recommended phase 2 dose is defined as the dose level with ≤ 1 out of 6 patients experiencing DLTs at the highest dose level below the MTD.
21 Day Cycle
Identify the Dose Limiting Toxicities (DLT) of ABT-888
Tidsramme: 21 Day Cycle
All adverse events, including DLTs, are graded according to the NCI CTCAE, v4.0. A DLT is defined as any grade 3 or higher non-hematologic toxicity, or any grade 4 hematologic toxicity, considered by the investigator to be related to the study drugs and occurring during Days 1-22 of Cycle 1.
21 Day Cycle

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Activity Objective - Preliminary assessment of the anti-tumor activity of ABT-888
Tidsramme: 21 day cycle
Response to study drugs is assessed at the end of each cycle according to the International Myeloma Working Group (IMWG) response criteria.
21 day cycle
Exploratory Objective - Preliminary assessment of potential biomarkers
Tidsramme: 24 months
Gene expression profiling is performed at baseline and compared between responders versus non-responders in order to identify a "treatment response signature". 2.5 mg of RNA will be extracted from plasma cells sorted from pre-treatment (D1, cycle 1) (n=20) and post-treatment (D11, cycle 1) (n=20) bone marrow aspirates collected from patients treated in the extension cohort. cRNAs will be hybridized onto the U133 Plus 2.0 gene chips and raw data files acquired using Affymetrix Microarray Suite version 5.1 software and analyzed with the Partek Genomics Suite v6.4.
24 months
Exploratory Objective - Determine in vivo the effect of ABT-888 on PARP inhibitors.
Tidsramme: 24 Months
Poly-ADP-ribose (PAR) levels are measured in sorted CD138+ plasma cells from pre-ABT-888 treatment on day 1 cycle1, as well as post ABT-888 treatment (within 4-6 hours) on days 4 and 11. PAR levels will be measured by standardized ELISA assays (HT PARP in vivo Pharmacodynamic Assay II™, Trevigen).
24 Months
Determine invivo the effects of Bortezomib on the plasma cells DNA genes expression and function
Tidsramme: 24 Months
Gene expression profiling is performed at baseline prior to treatment with bortezomib and on days 4 and 11 post bortezomib treatment. 2.5 mg of RNA will be extracted from plasma cells sorted from bone marrow aspirates collected from patients treated on trial. cRNAs will be hybridized onto the U133 Plus 2.0 gene chips and raw data files acquired using Affymetrix Microarray Suite version 5.1 software and analyzed with the Partek Genomics Suite v6.4.
24 Months

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

AHS Cancer Control Alberta

Samarbejdspartnere

Abbott
Tom Baker Cancer Centre

Efterforskere

  • Studiestol: Nizar J Bahlis, M.D., Tom Baker Cancer Centre, University of Calgary

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

1. oktober 2011

Primær færdiggørelse (Faktiske)

1. februar 2015

Studieafslutning (Faktiske)

10. februar 2015

Datoer for studieregistrering

Først indsendt

16. november 2011

Først indsendt, der opfyldte QC-kriterier

16. december 2011

Først opslået (Skøn)

20. december 2011

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

25. september 2017

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

21. september 2017

Sidst verificeret

1. september 2017

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • MM11-01
  • E24055 (Anden identifikator: CHREB- University of Calgary)

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Kliniske forsøg med Myelomatose

Kliniske forsøg med ABT-888/Bortezomib

Søg i lignende forsøg

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

CROs by country

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Betingelser

Sjældne sygdomme

Narkotikainterventioner

Kosttilskud

Sponsor / samarbejdspartnere

Placeringer

Abonner