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- Klinische proef NCT00906334
Efficacy and Safety of ON 01910.Na in Myelodysplastic Syndrome (MDS) Patients With Trisomy 8 or Classified as Intermediate-1, -2 or High Risk
22 juni 2017 bijgewerkt door: Onconova Therapeutics, Inc.
A Phase 2, Single-Arm Study To Assess The Efficacy and Safety Of 72-Hour Continuous Intravenous Dosing Of ON 01910.Na Administered Every Other Week in Myelodysplastic Syndrome Patients With Trisomy 8 or Classified as Intermediate-1, 2 or High Risk
This study will explore the efficacy and safety of a regimen of ON 01910.Na as a 48-hour continuous intravenous infusion once a week for 3 weeks of a 4-week cycle in MDS patients with Trisomy 8 or classified as Intermediate-1, -2 or High Risk who are not responding to current therapeutic options.
The rationale for this trial is based upon data from laboratory studies with ON 01910.Na and upon activity that has been observed in other clinical trials with ON 01910.Na in patients with MDS.
Studie Overzicht
Toestand
Voltooid
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
This is a phase 2, study in which 14 MDS patients with Trisomy 8 or classified as Intermediate-1, -2 and High risk who meet all other inclusion/exclusion criteria will receive ON 01910.Na 800 mg/m^2/24h as an continuous intravenous infusion (CIV) over 48 hours once a week for 3 weeks of a 4-week cycle.
As of Amendment 3 to the Protocol, the regimen is changed to 1800 mg/24h for 72 hours every other week for the first four 2-week cycles and every 4 weeks afterwards.
The total study duration is 31 weeks, which includes a 2-week screening phase, a 27-week dosing phase, and a 4-week follow-up phase that begins after the last dose of ON 01910.Na.
Beginning at week 4, and every 2 weeks thereafter, patients will be assessed for response.
Patients who drop out for any reason will not be replaced.
Patients who achieve by week 29 a complete or partial response or stabilization of their disease are eligible to receive an additional 24 weeks of ON 01910.Na 1800 mg/24 h over 72 hours per week of a 4-week cycle.
Studietype
Ingrijpend
Inschrijving (Werkelijk)
14
Fase
- Fase 2
Contacten en locaties
In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.
Studie Locaties
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California
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Stanford, California, Verenigde Staten, 94305
- Stanford Cancer Center
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Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
18 jaar en ouder (Volwassen, Oudere volwassene)
Accepteert gezonde vrijwilligers
Nee
Geslachten die in aanmerking komen voor studie
Allemaal
Beschrijving
Inclusion Criteria:
- Diagnosis of MDS confirmed within 2 weeks prior to study entry according to the World Health Organization (WHO) Criteria or the French-American-British (FAB) Classification.
- Trisomy 8 cytogenetics (simple or combined to other karyotypes) or patient classified as Intermediate-1 with bone marrow blasts equal to or greater than 5%, Intermediate-2 or High Risk MDS according to the IPSS score, or Patients with peripheral blood blasts equal to or greater than 5%.
- At least one cytopenia (Absolute Neutrophil Count < 1800/µl or Platelet Count <100,000/µl or Hemoglobin < 10 g/dL).
- Failure of, or insufficient response to Azacytidine or Decitabine administered for 4 to 6 cycles in patients classified as Intermediate-2 or High risk or to Erythrocyte stimulating agents (failure or insufficient response defined as transfusion dependence or Hemoglobin remaining below 10 g/dl) in Low or Intermediate-1 Risk Trisomy 8 patients.
- Failed to respond to, relapsed following, or opted not to participate in bone marrow transplantation.
- Off all other treatments for MDS (including filgrastim (G-CSF) and erythropoietin) for at least four weeks. As an exception, filgrastim (G-CSF) can be used before, during and after the protocol treatment for patients with documented febrile neutropenia (< 500/µl).
- ECOG Performance Status 0, 1 or 2.
- Willing to adhere to the prohibitions and restrictions specified in this protocol.
- Patient (or his/her legally authorized representative) must have signed an informed consent document indicating that he/she understands the purpose of and procedures required for the study and is willing to participate in the study.
Exclusion Criteria:
- Anemia due to factors other than MDS (including hemolysis or gastrointestinal bleeding).
- Hypoplastic MDS (cellularity <10%).
- Any active malignancy within the past year except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast.
- History of HIV-1 seropositivity.
- Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia.
- Active infection not adequately responding to appropriate therapy.
- Total bilirubin > 1.5 mg/dL not related to hemolysis or Gilbert's disease, ALT or AST > 2 X ULN.
- Serum creatinine > 2.0 mg/dL or calculated creatinine clearance < 60 ml/min/1.73 m^2.
- Ascites requiring active medical management including paracentesis, or hyponatremia (defined as serum sodium value of <134 Meq/L).
- Women patients who are pregnant or lactating; Male patients with female sexual partners who are unwilling to follow the strict contraception requirements described in this protocol; Patients who do not agree to use adequate contraceptive [including prescription oral contraceptives (birth control pills), contraceptive injections, intrauterine device (IUD), double-barrier method (spermicidal jelly or foam with condoms or diaphragm), contraceptive patch, or surgical sterilization] before entry and throughout the study; Female patients with reproductive potential who do not have a negative serum beta-HCG pregnancy test at screening.
- Major surgery without full recovery or major surgery within 3 weeks of ON 01910.Na treatment start.
- Uncontrolled hypertension (defined as a systolic pressure equal to or greater than 160 mmHg and/or a diastolic pressure equal to or greater than 110 mmHg).
- New onset seizures (within 3 months prior to the first dose of ON 01910.Na) or poorly controlled seizures
- Any concurrent investigational agent or chemotherapy, radiotherapy or immunotherapy.
- Treatment with standard MDS therapies or investigational therapy within 4 weeks of starting ON 01910.Na.
- Psychiatric illness/social situations that would limit the patient's ability to tolerate and/or comply with study requirements.
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
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: 800 mg/m^2 ON 01910.Na
800 mg/m^2 ON 01910.Na administered as a continuous intravenous infusion (CIV) over 24 hours for 48 hours (i.e. 2 consecutive 24-hour infusions) every week for the first 3 weeks of 4-week cycle.
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The original dosing regimen was 800 mg/m^2 ON 01910.Na.
Andere namen:
Per Amendment 3 to the Protocol, the dosing regimen was changed to 1800 mg ON 01910.Na.
Patients enrolled at the original dosing regimen could choose to remain in the original regimen or switch to the new regimen.
Andere namen:
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Experimenteel: 1800 mg ON 01910.Na
1800 mg ON 01910.Na administered as a continuous intravenous infusion (CIV) over 24 hours for 72 hours (i.e., 3 consecutive 24-hour infusions) every 2 weeks for the first four 2-week cycles and every 4 weeks afterwards.
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The original dosing regimen was 800 mg/m^2 ON 01910.Na.
Andere namen:
Per Amendment 3 to the Protocol, the dosing regimen was changed to 1800 mg ON 01910.Na.
Patients enrolled at the original dosing regimen could choose to remain in the original regimen or switch to the new regimen.
Andere namen:
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Overall Response Rate (ORR)
Tijdsspanne: 29 weeks
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The Overall Response Rate is defined as the proportion of patients who achieve a Complete Response, a Partial Response, A Complete Bone Marrow Response or a Hematologic Improvement (HI) according to the 2006 International Working Group (IWG) criteria.
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29 weeks
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Number of patients with adverse events
Tijdsspanne: From date of signing informed consent until 30 days after last dose of study drug up to 29 weeks
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The NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 will be used to determine the grade of adverse events.
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From date of signing informed consent until 30 days after last dose of study drug up to 29 weeks
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
---|---|---|
Time to Overall Response
Tijdsspanne: 29 weeks
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Time to Overall Response is calculated from date of first study drug administration to date of first occurrence of any of the following responses: Complete Response (CR), Partial Response (PR), Marrow Complete Response (BMCR) or Hematologic Improvement (HI) as defined by the 2006 International Working Group (IWG) criteria.
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29 weeks
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Duration of Response
Tijdsspanne: 29 weeks
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Duration of response is calculated from date of first occurrence of any of the following responses: Complete Response (CR), Partial Response (PR), Marrow Complete Response (BMCR) or Hematologic Improvement (HI) as defined by the 2006 International Working Group (IWG) criteria) until the date of disease progression.
Patients who did not have disease progression are censored at the last bone marrow or bone marrow morphology assessment date.
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29 weeks
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Bone Marrow Complete Response
Tijdsspanne: Weeks 5, 13, 21 and 29
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The proportion of patients who achieve a Bone Marrow Complete Response (BMCR) according to 2006 International Working Group (IWG) criteria.
Bone marrow blasts are determined in bone marrow differential count.
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Weeks 5, 13, 21 and 29
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Cytogenetic Response
Tijdsspanne: 29 weeks
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Cytogenetic Response is defined as the number of patients who achieve a cytogenic response according to 2006 International Working Group criteria.
Complete response is defined as the disappearance of the chromosomal abnormality without appearance of new ones.
Partial response is defined as at least 50% reduction of the chromosomal abnormality.
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29 weeks
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Neutrophil Response
Tijdsspanne: 29 weeks
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The number of patients who achieve a Neutrophil Response according to 2006 International Working Group (IWG).
Neutrophil Response is defined as at least a 100% increase and an absolute increase greater than 0.5 x 10^9/L.
Pretreatment values must be less than 1.0 x 10^9/L.
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29 weeks
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Platelet Response
Tijdsspanne: 29 weeks
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The number of patients who achieve a Platelet Response according to 2006 International Working Group (IWG).
Platelet Response is defined as an absolute of greater than or equal to 30 x 10^9 for patients starting with less than 20 x 10^9/L.
increase and an absolute increase greater than 0.5 x 10^9/L.
Pretreatment values must be less than 1.0 x 10^9/L.
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29 weeks
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Erythroid Response
Tijdsspanne: 29 weeks
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The number of patients who achieve an Erythroid Response according to 2006 International Working Group (IWG).
Erythroid Response is defined as a Hgb increase equal to or greater than 1.5 g/dL and a relevant reduction of units of red blood cells (RBC) transfusions by an absolute number of at least 4 RBC transfusions/8 weeks compared with the pretreatment transfusion number in the previous 8 wells.
Only RBC transfusions given for a Hgb of 9.0 g/dL or lower pretreatment will count in the RBC transfusion response evaluation.
Pretreatment values of Hgb must be lower than 11 g/dL.
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29 weeks
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Time to Disease Progression
Tijdsspanne: 29 weeks
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Time to Disease Progression is calculated from date of first dose of study drug administration to date of disease progression recorded on the hematology response assessment clinical report form.
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29 weeks
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Time to Acute Myeloid Leukemia (AML) Progression
Tijdsspanne: 29 and 53 weeks
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Time to Acute Myeloid Leukemia (AML) Progression is calculated from date of first study drug administration to date of AML progression recorded on the Off Study Summary clinical report form.
Patients who do not have AML disease progression are censored at the last bone marrow or bone marrow morphology assessment date.
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29 and 53 weeks
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Overall Survival
Tijdsspanne: 29 and 53 weeks
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Overall Survival is calculated from date of first study drug administration to date of death.
In event of no death prior to study termination or data analysis cutoff, overall survival is censored at the last known date patient was alive
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29 and 53 weeks
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Proportion of patients who achieve a Complete Hematologic Response
Tijdsspanne: Up to 29 weeks
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The proportion of patients who achieve a Complete Remission (CR) Hematologic Response according to 2006 International Working Group (IWG) criteria.
Bone marrow blasts are determined in bone marrow differential count.
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Up to 29 weeks
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The proportion of patients who achieve a Partial Remission (CR)
Tijdsspanne: Up to 29 weeks
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The proportion of patients who achieve a Partial Remission (PR) Hematologic Response according to 2006 International Working Group (IWG) criteria.
Bone marrow blasts are determined in bone marrow differential count.
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Up to 29 weeks
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Medewerkers en onderzoekers
Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.
Sponsor
Onderzoekers
- Hoofdonderzoeker: Peter L. Greenberg, MD, Stanford University
Publicaties en nuttige links
De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.
Algemene publicaties
- Garcia-Manero G, Fenaux P. Comprehensive Analysis of Safety: Rigosertib in 557 Patients with Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML). Blood Dec 2016, 128 (22) 2011; ASH 2016.
- Silverman LR, Greenberg P, Raza A, Olnes MJ, Holland JF, Reddy P, Maniar M, Wilhelm F. Clinical activity and safety of the dual pathway inhibitor rigosertib for higher risk myelodysplastic syndromes following DNA methyltransferase inhibitor therapy. Hematol Oncol. 2015 Jun;33(2):57-66. doi: 10.1002/hon.2137. Epub 2014 Apr 29.
- Navada SC, Silverman LR. The safety and efficacy of rigosertib in the treatment of myelodysplastic syndromes. Expert Rev Anticancer Ther. 2016 Aug;16(8):805-10. doi: 10.1080/14737140.2016.1209413. Epub 2016 Jul 15.
- Seetharam M, Fan AC, Tran M, Xu L, Renschler JP, Felsher DW, Sridhar K, Wilhelm F, Greenberg PL. Treatment of higher risk myelodysplastic syndrome patients unresponsive to hypomethylating agents with ON 01910.Na. Leuk Res. 2012 Jan;36(1):98-103. doi: 10.1016/j.leukres.2011.08.022. Epub 2011 Sep 14.
Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start
1 mei 2009
Primaire voltooiing (Werkelijk)
1 november 2013
Studie voltooiing (Werkelijk)
1 november 2013
Studieregistratiedata
Eerst ingediend
19 mei 2009
Eerst ingediend dat voldeed aan de QC-criteria
20 mei 2009
Eerst geplaatst (Schatting)
21 mei 2009
Updates van studierecords
Laatste update geplaatst (Werkelijk)
26 juni 2017
Laatste update ingediend die voldeed aan QC-criteria
22 juni 2017
Laatst geverifieerd
1 juni 2017
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
- Pathologische processen
- Neoplasmata
- Ziekte
- Beenmergziekten
- Hematologische ziekten
- Voorstadia van kanker
- Chromosoomafwijkingen
- Aneuploïdie
- Chromosoom duplicatie
- Syndroom
- Myelodysplastische syndromen
- Preleukemie
- Trisomie
- Fysiologische effecten van medicijnen
- Neurotransmitter agenten
- Moleculaire mechanismen van farmacologische werking
- Enzymremmers
- Antineoplastische middelen
- Proteïnekinaseremmers
- Glycine-agenten
- Glycine
- OP 01910
Andere studie-ID-nummers
- Onconova 04-17
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 ON 01910.Na
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Onconova Therapeutics, Inc.VoltooidNeoplasmata | Kanker | Geavanceerde kanker | Vaste tumorenVerenigde Staten
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Onconova Therapeutics, Inc.IngetrokkenMyelodysplastisch syndroomVerenigde Staten
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Onconova Therapeutics, Inc.VoltooidNeoplasmata | Kanker | Geavanceerde kanker | Vaste tumorenVerenigde Staten
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Onconova Therapeutics, Inc.VoltooidGeavanceerde vaste tumor | HepatoomVerenigde Staten
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Onconova Therapeutics, Inc.VoltooidGeavanceerde solide tumorenVerenigde Staten
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Onconova Therapeutics, Inc.VoltooidHoofd-hals plaveiselcelcarcinoom | Slokdarm plaveiselcelcarcinoom | Anale plaveiselcelcarcinoom | Cervicaal plaveiselcelcarcinoom | Plaveiselcelcarcinoom van de huid | Longplaveiselcelcarcinoom | Plaveiselcelcarcinoom van de penisVerenigde Staten
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First Affiliated Hospital of Zhejiang UniversityWerving
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M.D. Anderson Cancer CenterOnconova Therapeutics, Inc.BeëindigdLeukemie | Bloedarmoede | Myelofibrose | SplenomegalieVerenigde Staten
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National Heart, Lung, and Blood Institute (NHLBI)VoltooidMyelodysplastisch syndroom (MDS)Verenigde Staten
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Onconova Therapeutics, Inc.IngetrokkenMyelodysplastisch syndroomVerenigde Staten