Study of DSP-7888 in Patients With Myelodysplastic Syndrome (MDS)

Phase 1/2 Study of DSP-7888 in Patients With Myelodysplastic Syndrome (MDS)

This is a phase 1/2, uncontrolled, open-label, multicenter study in patients with MDS for whom no effective therapies currently exist.

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndrome
• Intervention / Treatment: Drug: DSP-7888

Detailed Description

This is a phase 1/2, uncontrolled, open-label, multicenter study in patients with MDS for whom no effective therapies currently exist. In the Phase 1 part, high risk and low risk patients with MDS requiring additional treatment will be enrolled, and two different dose levels of DSP-7888 (3.5 and 10.5 mg/body) will be investigated in a stepwise manner starting with the lower dose using the 3+3 design, to determine the MTD and the RD for the Phase 2 part based on DLT evaluation during the 29 days following the initial dose of DSP-7888. In the Phase 2 part, DSP-7888 therapy at the RD determined by the Phase 1 part will be administered to high risk patients with MDS who had received and not responded to azacitidine as a standard treatment.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan
    • Kyushu University Hospital
  • Fukuoka, Japan
    • National Hospital Organization Kyushu Medical Center
  • Okayama, Japan
    • Okayama City General Medical Center Okayama City Hospital
  • Chiba
    • Narita, Chiba, Japan
      • Japanese Red Cross Narita Hospital
  • Hiroshima
    • Fukuyama, Hiroshima, Japan
      • Chugoku Central Hospital
  • Kanagawa
    • Yokohama, Kanagawa, Japan
      • Yokohama Municipal Citizen's Hospital
  • Kochi
    • Nankoku, Kochi, Japan
      • Kochi Medical School Hospital
  • Miyagi
    • Sendai, Miyagi, Japan
      • Sendai Medical Center
  • Okayama
    • Kurashiki, Okayama, Japan
      • Kurashiki Central Hospital
  • Osaka
    • Osakasayama, Osaka, Japan
      • Kindai University Hospital
    • Suita, Osaka, Japan
      • Osaka University Hospital
  • Tokyo
    • Itabashi-ku, Tokyo, Japan
      • Tokyo Metropolitan Geriatric Hospital
    • Shibuya-ku, Tokyo, Japan
      • Japanese Red Cross Medical Center
    • Shinagawa-ku, Tokyo, Japan
      • NTT Medical Center Tokyo
    • Shinjuku-ku, Tokyo, Japan
      • Keio University Hospital
    • Tachikawa, Tokyo, Japan
      • National Hospital Organization Disaster Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

[For Phase 1 part only]

• Patients with a diagnosis of MDS according to either the fourth edition of the WHO classification or the FAB classification, with the exception of those with chronic myelomonocytic leukemia (CMML) or refractory anemia with excess blasts in transformation (RAEB-t)
• Patients with an International Prognostic Scoring System (IPSS) score of ≧ 1.5 at enrollment, or patients with an IPSS score of < 1.5 who require additional treatment to supportive therapy in the opinion of the investigator or subinvestigator.
• Patients who will be able to be hospitalized from the initial dose of DSP-7888 until the end of the post-initial dose observation (Patients may be permitted to have a temporary overnight leave during the hospitalization.)

[For Phase 2 part only]

• Patients with a diagnosis of MDS according to either the fourth edition of the WHO classification or the FAB classification
• Patients with an IPSS score of ≧ 1.5 at enrollment, or patients with an IPSS score of < 1.5 with myeloblasts ≧ 5%
• Patients who received at least one cycle of azacitidine therapy

[For both Phase 1 and 2 parts]

• Patients with a peripheral white blood cell count of ≦12,000/mm3 within 4 weeks (28 days) before enrollment (on the basis of the most recent data during the period if multiple data are available)
• Patients aged ≧20 years at the time of informed consent
• Patients who have provided written voluntary consent in person to participate in this study after fully receiving and understanding the information about this study, including study objectives, contents, expected pharmacological actions and effects, and foreseeable risks
• Patients with an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 to 2 at enrollment
• Patients with a life expectancy of ≧ 3 months (90 days)
• Patients for whom no standard therapies are currently available, including transplant treatments such as allogeneic stem cell transplant
• Patients with a human leukocyte antigen (HLA) type of HLA-A*24:02 or HLA-A*02:01/06

• Patients with adequate major organ functions meeting the following criteria on the basis of laboratory data within 4 weeks (28 days) before enrollment (if multiple data are available, most recent data during the period)

  • Serum creatinine: ≦ 2-fold the upper limit of the normal range of the study site (ULN)
  • Total bilirubin: ≦2-fold the ULN
  • AST, ALT: ≦3-fold the ULN
• Female patients of childbearing potential and male patients with female partners of childbearing potential must agree to use appropriate contraception from the time of consent until 6 months (180 days) after the last dose of the study drug to avoid pregnancy
• Female patients of childbearing potential must have a negative pregnancy test (urine) within 4 weeks (28 days) before enrollment

Exclusion Criteria:

• Patients with a dry tap on bone marrow aspiration before enrollment
• Patients with grade ≧ 3 infection according to the Common Terminology Criteria for Adverse Events, version 4.0 (CTCAE v4.0)
• Patients with a positive test result for HIV antibody, HBs antigen or HCV antibody
• Patients with any intracranial metastasis that is symptomatic or requires treatment
• Patients with active multiple cancers (synchronous multiple cancers, or metachronous multiple cancers with a disease-free period of ≦ 5 years, with the exception of carcinoma in situ, mucosal carcinoma, or other such carcinomas curatively treated with local therapy)
• Patients who had myocardial infarction within 6 months (180 days) before enrollment
• Patients with significant diseases at enrollment that may affect study treatment, such as New York Heart Association (NYHA) Functional Class III or IV heart disease, CTCAE v4.0 grade ≧ 3 arrhythmia, angina pectoris, abnormal electrocardiogram findings, interstitial pneumonia or pulmonary fibrosis
• Patients with uncontrollable complications
• Patients with CTCAE v4.0 grade ≧2 hemorrhage
• Patients who underwent allogeneic hematopoietic stem cell transplant

• Patients who received any of the following treatments within the specified period before enrollment:

  • Surgery, radiotherapy, chemotherapy (including molecular-targeted drugs): 4 weeks (28 days)
  • Immunosuppressants, cytokine preparations (excluding G-CSF): 4 weeks (28 days)
  • Endocrine therapy, immunotherapy (including biological response modifier therapy): 2 weeks (14 days)
• Pregnant women or breastfeeding women
• Patients with concurrent autoimmune disease or a history of chronic or recurrent autoimmune disease, or patients who require long-term systemic steroid therapy (excluding therapy given on a PRN basis)
• Patients with any ongoing CTCAE v4.0 grade ≧ 2 adverse effects of prior treatment (excluding alopecia and phlebitis)
• Patients who received any investigational product or post-marketing study drug within 4 weeks (28 days) before enrollment
• Patients with a history of allergy to any oily drug products
• Patients who previously received DSP-7888, any other WT1 peptide, or WT1 immunotherapy
• Patients who are inappropriate for participation in the study for other reasons in the opinion of the investigator or subinvestigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DSP-7888	Drug: DSP-7888; 3.5-10.5 mg/body,Id every 2-4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival （OS）	Participants follow-up for overall survival will occur. Maximum follow-up time is 2 year after the initial administration of the last subject.	24 months
Safety and tolerability assessed by adverse events (AEs), serious adverse events (SAEs), dose-limiting toxicity (DLT)	Safety and tolerability assessed by adverse events (AEs), serious adverse events (SAEs), dose-limiting toxicity (DLT)	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate（ORR）	HR（Hematologic Response）, HI（Hematologic improvement） and Cytogenetic response assessed by IWG MDS response criteria 2006	6 months
TI （Blood transfusion independence）	Defined as the absence of any RBC or PLT transfusion for any consecutive 8 weeks	6 months
Time to transformation to AML	Participants follow-up for time to transformation to AML will occur. Maximum follow-up time is 2 year after the initial administration of the last subject.	24 months
Biomarkers	Explore efficacy related biomarkers assessed by delayed-type hypersensitivity (DTH) reactions to WT1 peptide and WT1 peptide-specific CTL-induction activity	6 months

Collaborators and Investigators

• Sponsor: Sumitomo Pharma Co., Ltd.
• Investigators: Study Director: Sumitomo Pharma Co., Ltd. Japan, Sumitomo Pharma Co., Ltd.

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): March 1, 2020
• Study Completion (Actual): March 1, 2020

Study Registration Dates

• First Submitted: April 23, 2015
• First Submitted That Met QC Criteria: May 5, 2015
• First Posted (Estimate): May 6, 2015

Study Record Updates

• Last Update Posted (Actual): April 12, 2022
• Last Update Submitted That Met QC Criteria: April 9, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: MDS; Myelodysplastic Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia
• Other Study ID Numbers: DB650027