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

NCT02197676 | Completed Phase 2

• 1 other identifier: GFM-SGI-110
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 27

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.

Conditions

MDS

Outcome Measures

Primary Outcomes (1)

• Response rate

  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

  6 month

Secondary Outcomes (2)

• Duration of response

  4 years

• Adverse event

  After 1 month

Study Arms (1)

SGI-110

EXPERIMENTAL

Drug: SGI-110 administration

Interventions

SGI-110 administration DRUG

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 Patients with no response (NR) to treatment will be withdrawn from the protocol after the last treatment Cycle.

SGI-110

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Understand the study drug is expected to have a teratogenic risk
• 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.
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Groupe Francophone des Myelodysplasies: lead
• Astex Pharmaceuticals, Inc.: collaborator

Study Sites (27)

CH Angers

Angers, 49 000, France

Location

CH Avignon

Avignon, 84000, France

Location

Centre Hospitalier de La Cote Basque

Bayonne, 64100, France

Location

Hôpital Avicenne

Bobigny, 93 000, France

Location

CHU Clémenceau

Caen, 14033, France

Location

CHU Henri Mondor

Créteil, 94010, France

Location

CHU de Grenoble

Grenoble, 38043, France

Location

Centre Hospitalier du Mans

Le Mans, 72000, France

Location

CHRU Limoges

Limoges, 87046, France

Location

CH Lyon Sud

Lyon, 69495, France

Location

Hôpital Paoli Calmettes

Marseille, 13273, France

Location

Centre Hospitalier de Meaux

Meaux, 77100, France

Location

Clinique Beausoleil (Montpellier)

Montpellier, 34000, France

Location

CHU de nantes

Nantes, 44093, France

Location

Centre Catherine de Sienne (Nantes)

Nantes, 44277, France

Location

CHU de Nice - Hopital de l'Archet 1

Nice, 06 202, France

Location

CHR Orléans

Orléans, 45000, France

Location

Hopital St Louis T4

Paris, 75475, France

Location

Centre Hospitalier Joffre

Perpignan, 66046, France

Location

CHU de Haut-Lévèque

Pessac, 33604, France

Location

CHU de Poitiers

Poitiers, 86000, France

Location

Centre Hospitalier de la région d'Annecy

Pringy, 74374, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Chu Purpan

Toulouse, 31059, France

Location

Hopital Purpan Service d'Hématologie Clinique

Toulouse, France

Location

CHU Bretonneau

Tours, 37044, France

Location

CHU Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

Study Officials

• Pierre Fenaux, PHD

  GFM

  PRINCIPAL INVESTIGATOR

• Marie Sébert, PHD

  Saint-Louis Hospital, PARIS

  PRINCIPAL INVESTIGATOR

• Lionel Ades, PHD

  Saint Louis hospital, Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2014
• First Posted: July 23, 2014
• Study Start: August 4, 2014
• Primary Completion: February 6, 2016
• Study Completion: April 23, 2018
• Last Updated: December 6, 2018

Record last verified: 2018-12

Locations

FR (27)