ClinicalTrials.gov
ClinicalTrials.gov Menu

A Phase II Trial of SGI-110 in Patients With IPSS High and Int 2 Myelodysplastic Syndrome, Acute Myeloid Leukemia With 20-30% Marrow Blasts or Chronic Myelomonocytic Leukemia Type 2 Not Responding to Azacitidine or Decitabine After at Least 6 Courses or Relapsing After a Response

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02197676
Recruitment Status : Completed
First Posted : July 23, 2014
Last Update Posted : July 25, 2018
Sponsor:
Collaborator:
Astex Pharmaceuticals
Information provided by (Responsible Party):
Groupe Francophone des Myelodysplasies

Brief Summary:
Treatment of patients with WHO defined IPSS int 2 and high risk MDS , AML with 20-30% marrow blasts and CMML type 2, after failure of azacitidine or decitabine exposure for at least 6 courses, or relapse after initial response.

Condition or disease Intervention/treatment Phase
MDS Drug: SGI-110 administration Phase 2

Detailed Description:

All eligible patients will be treated with SGI-110 for 9 cycles of 28 days.

Patients who meet eligibility criteria will be administered subcutaneous SGI-110 at 60mg/m²/d one time daily for 5 days. Each cycle will last 28 days with SGI-110 starting on day 1 of each cycle. Patients will receive at least 9 cycles unless overt progression is documented. (Overt progression will be defined by the presence of more than 30% marrow blasts and doubling of marrow blast percentage from onset of SGI-110). Dose reduction to 45 and even 30 mg/m²/d will be made in case of toxicity.

Patients with Complete Remission (CR), Partial Remission (PR), marrow CR, Hematological Improvement (HI) or stable disease (SD) after 6 Cycles of therapy (IWG 2006 criteria) may receive 3 additional cycles. Response will be re-evaluated after 9 cycles. Patients with no response (NR) to treatment after 9 cycles will be withdrawn from the protocol. Patients with progression at any time will be withdrawn from the protocol after the last treatment Cycle.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 56 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of SGI-110 in Patients With IPSS High and Int 2 Myelodysplastic Syndrome, Acute Myeloid Leukemia With 20-30% Marrow Blasts or Chronic Myelomonocytic Leukemia Type 2 Not Responding to Azacitidine or Decitabine After at Least 6 Courses or Relapsing After a Response
Actual Study Start Date : August 4, 2014
Actual Primary Completion Date : February 6, 2016
Actual Study Completion Date : April 23, 2018


Arm Intervention/treatment
Experimental: SGI-110 Drug: SGI-110 administration

SGI-110 will be administered SC at 60 mg/m²/day x5 consecutive days for each cycle. Cycle duration is 28 days. Patients with Complete Remission (CR), Partial Remission (PR), marrow CR or Hematological Improvement (HI) after 6 Cycles of therapy (IWG 2006 criteria) may continue treatment until progression.

A dose reduction to 45 and even 30 mg/m²/day will be made in case of haematological toxicity. Patients with no response (NR) to treatment will be withdrawn from the protocol after the last treatment Cycle.





Primary Outcome Measures :
  1. Response rate [ Time Frame: 6 month ]
    Number of complete Remission (CR), CR with incomplete hematological recovery (CRi), Partial Remission (PR), Marrow CR and Hematological Improvement (HI) according to IWG 2006 criteria after 6 treatment cycles


Secondary Outcome Measures :
  1. Duration of response [ Time Frame: 4 years ]
    Measured from the date an objective response was achieved to the date of relapse or progression (cf. definition in appendix 5) or the date of last contact if no event occurred.

  2. Adverse event [ Time Frame: After 1 month ]
    Patients must have received at least one dose of treatment in order to be considered evaluable for toxicity.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Myelodysplastic syndrome including the following categories of the WHO classification: refractory anemia with excess blasts (RAEB), non-proliferative chronic myelomonocytic leukemia (CMML) (leukocytes < 13 G/L but > 10% marrow blasts), AML with 20-30% marrow blasts (RAEB-T according to the FAB classification), at screening time.
  • Prior treatment with azacitidine or decitabine for at least 6 courses without response(CR, PR, marrow CR or stable disease with HI according to IWG 2006 criteria) or relapsing after a response. Non responders will be eligible only in the absence of overt progression, ie AML progression (if patients had no AML at onset of azacitidine/decitabine) or doubling of marrow blast percentage between onset of azacitidine/decitabine and screening
  • IPSS score >1 (IPSS: Int-2 or High).
  • Age ≥ 18 years.
  • Normal liver function, defined by total bilirubin and transaminases less than 1.5 times the upper limit of normal.
  • Normal renal function, defined by creatinine less than 1.5 times the upper limit of normal, creatinine clearance ≥ 50 mL/min.
  • Patient is known not to be refractory to platelet transfusions.
  • Written informed consent.
  • Patient must understand and voluntarily sign consent form.
  • Patient must be able to adhere to the visit schedule as outlined in the study and follow protocol requirements.
  • ECOG performance status between 0-2 at the time of screening.
  • Women of chilbearing potential* must:

    1. Understand the study drug is expected to have a teratogenic risk
    2. Agree to have a medically supervised pregnancy test on the day of the study visit or in the 3 days prior to the study visit once the subject has been on effective contraception for at least 4 weeks. This requirement also applies to women of childbearing potential who practice complete and continued abstinence. The test should ensure the subject is not pregnant when she starts treatment.
    3. Agree to have a medically supervised pregnancy test every 4 weeks including 2 months after the end of study treatment, except in the case of confirmed tubal sterilization. These pregnancy tests should be performed on the day of the study visit or in the 3 days prior to the study visit. This requirement also applies to women of childbearing potential who practice complete and continued abstinence
    4. Agree to use, and to be able to comply with, Two medically acceptable contraceptive measures without interruption, 4 weeks before starting study drug throughout the entire duration study drug therapy (including doses interruptions) and for 2 months after the end of the study drug therapy even if she has amenorrhoea. This applies unless the subject commits to absolute and continuous abstinence confirmed on a monthly basis, to avoid pregnancy for the duration of study.
    5. Understand that even if she has amenorrhea, she must follow all the advice on effective contraception.
    6. She understands the potential consequences of pregnancy and the need to rapidly consult if there is a risk of pregnancy
  • Men must: Agree to not conceive during the treatment and to use effective contraception during the treatment period (including periods of dose reduction or temporary suspension) and for a further 2 3 months after the end of treatment if their partner is of childbearing potential.

Exclusion Criteria:

  • Severe infection or any other uncontrolled severe condition.
  • Significant cardiac disease - NYHA Class III or IV or having suffered a myocardial infarction in the last 6 months.
  • Less than 30 days since prior treatment with growth factors (EPO, G-CSF).
  • Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea. The patient must have recovered from all acute toxicities from any previous therapy.
  • Active cancer, or cancer during the year prior to trial entry other than basal cell carcinoma, or carcinoma in situ of the cervix or breast.
  • Patient already enrolled in another therapeutic trial of an investigational drug.
  • HIV infection or active hepatitis B or C.
  • Women who are or could become pregnant or who are currently breastfeeding.
  • Any medical or psychiatric contraindication that would prevent the patient from understanding and signing the informed consent form.
  • Patient eligible for allotransplantation.
  • Known allergy to SGI-110 or any of its excipients.
  • No affiliation to an insurance system.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02197676


Locations
France
CH Angers
Angers, France, 49 000
CH Avignon
Avignon, France, 84000
Centre Hospitalier de La Cote Basque
Bayonne, France, 64100
Hôpital Avicenne
Bobigny, France, 93 000
CHU Clémenceau
Caen, France, 14033
CHU Henri Mondor
Créteil, France, 94010
CHU de Grenoble
Grenoble, France, 38043
Centre Hospitalier du Mans
Le Mans, France, 72000
CHRU Limoges
Limoges, France, 87046
CH Lyon Sud
Lyon, France, 69495
Hôpital Paoli Calmettes
Marseille, France, 13273
Centre Hospitalier de Meaux
Meaux, France, 77100
Clinique Beausoleil (Montpellier)
Montpellier, France, 34000
CHU de nantes
Nantes, France, 44093
Centre Catherine de Sienne (Nantes)
Nantes, France, 44277
CHU de Nice - Hopital de l'Archet 1
Nice, France, 06 202
CHR Orléans
Orléans, France, 45000
Hopital St Louis T4
Paris, France, 75475
Centre Hospitalier Joffre
Perpignan, France, 66046
CHU de Haut-Lévèque
Pessac, France, 33604
CHU de Poitiers
Poitiers, France, 86000
Centre Hospitalier de la région d'Annecy
Pringy, France, 74374
Centre Henri Becquerel
Rouen, France, 76038
Chu Purpan
Toulouse, France, 31059
Hopital Purpan Service d'Hématologie Clinique
Toulouse, France
CHU Bretonneau
Tours, France, 37044
CHU Brabois
Vandœuvre-lès-Nancy, France, 54511
Sponsors and Collaborators
Groupe Francophone des Myelodysplasies
Astex Pharmaceuticals
Investigators
Principal Investigator: Pierre Fenaux, PHD GFM
Principal Investigator: Marie Sébert, PHD Saint-Louis Hospital, PARIS
Principal Investigator: Lionel Ades, PHD Saint Louis hospital, Paris

Responsible Party: Groupe Francophone des Myelodysplasies
ClinicalTrials.gov Identifier: NCT02197676     History of Changes
Other Study ID Numbers: GFM-SGI-110
First Posted: July 23, 2014    Key Record Dates
Last Update Posted: July 25, 2018
Last Verified: July 2018

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Myelodysplastic-Myeloproliferative Diseases
Azacitidine
Decitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors