Phase 1 Study of CC-486 in Japanese Subjects With Hematological Neoplasms

NCT01908387 | Terminated Phase 1 DMC

• 1 other identifier: CC-486-MDS-001
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 3

Brief Summary

To identify the maximum tolerated dose (MTD) of oral azacitidine on different treatment schedules in Japanese subjects with hematological neoplasms

Conditions

Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Acute Myeloid Leukemia; Multiple Myeloma; Non-Hodgkin Lymphoma; Hodgkin Lymphoma

Keywords

Oral azacitidine; CC-486; Hematological neoplasms; Phase 1

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicities

  Number of subjects experiencing dose limiting toxicity during the first 28-day cycle

  For 28 days

Secondary Outcomes (14)

• Number of participants with adverse events.

  Up to 4 years

• Pharmacokinetics - Cmax

  On day 1 and day 8

• Pharmacokinetics - Tmax

  On day 1 and day 8

• Pharmacokinetics - AUCt

  On day 1 and day 8

• Pharmacokinetics - AUC Zero to Infinity

  On day 1 and day 8

Study Arms (1)

Oral azacitidine

EXPERIMENTAL

Drug: Oral azacitidine

Interventions

Oral azacitidine DRUG

100 mg to 300 mg oral azacitidine once daily for 14 days or 21 days of the initial 28-day cycle

Also known as: CC-486

Oral azacitidine

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Eighteen years of age to 80 years of age at the time of signing the informed consent document; 2. Understand and voluntarily sign an informed consent document prior to any study related assessments and/or procedures being conducted; 3. Able to adhere to the study visit schedule and other protocol requirements; 4. Have a documented diagnosis of one of the following:
• Myelodysplastic syndromes or Chronic myelomonocytic leukemia (based on a bone marrow aspirate or bone marrow biopsy) or;
• Acute myeloid leukemia (based on a bone marrow aspirate or bone marrow biopsy), limited to those subjects for whom standard curative or palliative measures do not exist or are no longer effective or;
• Multiple myeloma, limited to those subjects for whom standard curative or palliative measures do not exist or are no longer effective or;
• Non-Hodgkin lymphoma or Hodgkin lymphoma, limited to those subjects for whom standard curative or palliative measures do not exist or are no longer effective; 5. For subjects with myelodysplastic syndromes only, have at least one of the following:
• Hemoglobin level ≤ 9.0 g/dL;
• Platelet count ≤ 75,000 /μL;
• Red blood cell transfusion-dependent as defined by:
• Average red blood cell transfusion requirement of ≥ 4 units per 28 days confirmed for a minimum of 84 days prior to starting study treatment. Hemoglobin levels within 7 days prior to administration of an red blood cell transfusion must be ≤ 9.0 g/dL in order for the transfusion to be counted towards red blood cell transfusion-dependent status. Red blood cell transfusions administered when hemoglobin levels were \> 9.0 g/dL and/or red blood cell transfusions administered for elective surgery will not qualify as a required transfusion for the purpose of providing evidence of red blood cell transfusion-dependent status. Note that 4 units of red blood cell in Japan is equivalent to 2 units of red blood cell outside of Japan;
• No consecutive 42 days that are red blood cell -transfusion-free during the 84 days prior to starting study treatment;
• Platelet transfusion-dependent as defined by:
• Have at least two separate platelet transfusion episodes during 56 days prior to starting study treatment. Platelet transfusions administered for elective surgery will not qualify as a required transfusion for the purpose of providing evidence of platelet transfusion-dependent status;
• No consecutive 28 days that are platelet-transfusion-free during the 56 days prior to starting study treatment; 6. Eastern Cooperative Oncology Group performance status of 0 or 1; 7. Females of childbearing potential (FCBP: a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal \[ie, amenorrhea following cancer therapy does not rule out childbearing potential\] for at least 24 consecutive months \[ie, has had menses at any time in the preceding 24 consecutive months\]) must:
• Agree to use at least two effective contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner; injectable and implantable hormonal contraceptive have not been approved in Japan as of March 2013) throughout the study, and for 3 months following the last dose of oral azacitidine and;
• Have a negative serum pregnancy test (sensitivity of at least 25 mIU/mL) at screening and;

You may not qualify if:

• Hypoplastic myelodysplastic syndromes defined as bone marrow cellularity of \< 20%;
• Atypical chronic myeloid leukemia and unclassifiable myeloproliferative neoplasms. Subjects with white blood cell counts ≥ 12,000/μL must be excluded (for subjects with acute myeloid leukemia: subjects with white blood cell counts ≥ 15,000/μL must be excluded, and for subjects with chronic myelomonocytic leukemia: subjects with white blood cell counts ≥ 20,000/μL must be excluded);
• Active central nerve system lymphoma unless the subject has been previously treated and remains asymptomatic for 3 months;
• Dry tap bone marrow aspirate due to myelofibrosis, and/or myelofibrosis accompanied by splenomegaly;
• Percentage of neoplasm cells in bone marrow more than 50%;
• Prior treatment with azacitidine or other hypomethylating agent that was discontinued due to adverse event related to that therapy except adverse events related to topical reactions related to injection of azacitidine;
• Prior allogeneic or autologous stem cell transplant;
• History of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis), celiac disease (ie, sprue), prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect that would interfere with the absorption, distribution, metabolism or excretion of the study drug and/or predispose the subject to an increased risk of gastrointestinal toxicity;
• Thrombocytopenia secondary to other possible causes, including medication(s), congenital disorder(s), immune disorder(s) (eg, idiopathic thrombocytopenic purpura \[ITP\]), or microvascular disorder(s) (eg, disseminated intravascular coagulation, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura);
• Treatment with any anticancer therapy (standard or investigational) within the previous 21 days prior to the first dose of study drug or less than full recovery (CTCAE grade 1) from the clinically significant toxic effects of that treatment. Treatment with hydroxyurea within the previous 28 days prior to the first dose of study drug must be excluded;
• Concurrent use of corticosteroids, except for subjects on a stable or decreasing dose for at least 1 week prior to starting study treatment for medical conditions other than primary diseases. Topical use of corticosteroids is permitted regardless of dose
• Prior history of malignancies, other than myelodysplastic syndromes, chronic myelomonocytic leukemia, acute myeloid leukemia, multiple myeloma, non-hodgkin lymphoma, or hodgkin lymphoma, unless the subject has been free of the disease for ≥ 3 years. Exceptions include the following:
• Basal or squamous cell carcinoma of the skin;
• Carcinoma in situ of the cervix or breast;
• Incidental histological finding of prostate cancer (Tumor nodes metastasis \[TNM\] stage of T1a N0M0 or T1b N0M0);

Sponsors & Collaborators

• Celgene Corporation: lead

Study Sites (3)

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan

Location

National Cancer Center Hospital

Tokyo, Tokyo, 104-0045, Japan

Location

The Cancer Institute Hospital of JFCR

Tokyo, Tokyo, 135-8550, Japan

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic; Leukemia, Myeloid, Acute; Multiple Myeloma; Lymphoma, Non-Hodgkin; Hodgkin Disease; Hematologic Neoplasms

Interventions

Azacitidine; cc-486

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Lymphoma; Lymphatic Diseases; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Toru Sasaki, Director

  Celgene K.K.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2013
• First Posted: July 25, 2013
• Study Start: July 1, 2013
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: July 28, 2015

Record last verified: 2015-07

Locations

JP (3)