CC-4047 (Pomalidomide) for Graft vs. Host Disease
A Phase 2, Open-Label, Single-Arm, Pilot Study of Safety and Efficacy of CC-4047 (Pomalidomide) in Patients With Advanced Chronic Graft-Versus-Host Disease Developing After Allogeneic Hematological Stem Cell Transplantation
調査の概要
詳細な説明
Chronic Graft vs. Host Disease is a major complication after allogeneic hematopoietic stem cell transplantation developing in 30 - 70% of patients. It is a multisystem alloimmune and autoimmune disorder with a negative impact on quality of life and functional status, increased need for extended immunosuppression and is the leading cause of late transplant related mortality.
CC-4047 is a novel immune modulatory drug that is a thalidomide analog with a 4,000 fold greater inhibition of TNF-α production related to thalidomide. Several features of CC-4047 suggest that this drug may be useful in treating chronic GVHD including in vitro suppression of TNF-α production, increasing Th1 and stimulation of IL-12 and sIL-Rα.
This study is an open-label, single-arm, pilot study of efficacy and safety of CC-4047 in patients with advanced chronic GvHD who failed to achieve a response with high-dose corticosteroids or second line systemic immunosuppressive therapy.
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
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Missouri
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St. Louis、Missouri、アメリカ、63122
- Washington University School of Medicine
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Patient must meet all of the following inclusion criteria:
- Must be greater than or equal to 18 years of age at the time of consent.
- Must be able to adhere to the study visit schedule and other protocol requirements.
- Chronic graft versus host disease (GHVD) developing after allogeneic hematological stem cell transplantation diagnosed using NIH criteria for diagnosis and staging of chronic GvHD (including both "classic chronic GvHD" and "overlap syndrome")
- Must have moderate or severe chronic GvHD according to Global Staging System for Chronic GvHD or mild chronic GvHD with platelet count less than 100 x 109/L
- Must have failed to achieve response to high dose corticosteroid (average 0.5 mg/kg/day prednisone or equivalent for greater than or equal to 8 weeks), or have failed second line systemic immunosuppressive therapy.
- If taking corticosteroids at the time of enrollment, must be on stable or tapering schedule without corticosteroid pulses in the preceding 8 weeks.
- If taking secondary systemic immunosuppressive therapy at the time of enrolment, must be on stable or tapering schedule in the preceding 4 weeks.
- Karnofsky performance score (KPS) greater than or equal to 60%.
- Life expectancy greater than or equal to 3 months.
- Female of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse for at least 28 days before starting study drug, while participating in the study, and for at least 28 days after discontinuation from the study. The two methods of reliable contraception must include one highly effective method (i.e. intrauterine device (IUD), hormonal [birth control pills, injections, or implants], tubal ligation, partner's vasectomy) and one additional effective (barrier) method (i.e. latex condom, diaphragm, cervical cap). FCBP must be referred to a qualified provider of contraceptive methods if needed.
- FCBP must agree to pregnancy testing and contraceptive counseling every 28 days during the study. FCBP must also refrain from donating blood and/or egg while participating in the study and for at least 28 days after discontinuation from this study
- FCBP must have two negative pregnancy tests (sensitivity of at least 25 mIU/mL) prior to starting study drug. The first pregnancy test must be performed within 10-14 days prior to the start of study drug and the second pregnancy test must be performed within 24 hours prior to the start of study drug.
- Must agree to abstain from breastfeeding during study participation and for at least 28 days after study drug discontinuation.
- Male Subjects must agree to complete abstinence or to use a condom during sexual contact with with a pregnant female or a female of childbearing potential while participating in the study and for at least 90 days following study drug discontinuation even if he has undergone a successful vasectomy
- Must agree to counseling about sexual contact and the potential risks of fetal exposure to pomalidomide every 28 days.
- Male subjects will be warned that sharing study drug is prohibited
- Must agree to abstain from donating blood for at least 28 days following discontinuation of the study drug.
- Must agree to abstain from donating semen or sperm during study participation and for at least 90 days after study drug discontinuation.
- Must agree that if a pregnancy or a positive pregnancy test does occur in a the partner of a male study subject during study participation, the investigator must be notified immediately
- Patients must agree to not share study drug with anyone during participation in the study.
- Must understand and voluntarily sign an informed consent form, or must have a legally authorized representative who is able and willing to voluntarily sign an informed consent form on behalf of the patient.
Exclusion Criteria:
- Pregnant or lactating females.
- New immunosuppressive therapy started within the preceding 4 weeks.
- Extracorporeal photopheresis within the preceding 3 months.
- Hypersensitivity to any immune modulator drug (IMiD™).
- Unable to take prophylactic anticoagulation.
- Any condition which places the patient at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
- Acute, persistent, recurrent or late-onset acute GvHD defined by NIH criteria.
Any of the following laboratory values at registration:
- absolute neutrophil count (ANC) less than 1.0 x 109/L,
- platelets less than 75 x 109/L, or
- creatinine clearance less than 50 mL/min (Cockroft-Gault formula).
- Uncontrolled infection requiring systemic antibiotics.
- Known human immunodeficiency virus (HIV), hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection.
- Known uncontrolled arrhythmias or symptomatic heart disease or left ventricular ejection fraction less than 40% (an ECHO should be performed as clinically indicated)
- Recurrence of cancer for which the transplant was done except for presence of minimal residual disease by PCR.
- Other cancer less than or equal to 2 years prior study-entry except:
- Basal cell carcinoma of the skin,
- Squamous cell carcinoma of the skin,
- Carcinoma in situ of the cervix,
- Carcinoma in situ of the breast, or
- Prostate cancer (Tumor, Node, Metastasis [TNM] stage T1a or T1b)
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:なし
- 介入モデル:単一グループの割り当て
- マスキング:なし(オープンラベル)
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的:CC-4047 Arm
CC-4047 2 mg orally every day for 1 course (12 weeks or 84 days).
Every 28 days of treatment are considered as 1 cycle and every 3 cycles are are considered as 1 course of treatment.
A total of 4 courses of treatment are planned (12 months).
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他の名前:
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この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Overall Response (Complete Response + Partial Response + Other)
時間枠:1 year after last dose of CC-4047
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1 year after last dose of CC-4047
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Safety as Measured by the Most Common Adverse Effects and Reasons for Dose Reductions or Study-discontinuation
時間枠:30 days after last dose of CC-4047 or until resolution of event
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-Toxicities will be graded according to the NCI CTCAE v3.0.
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30 days after last dose of CC-4047 or until resolution of event
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協力者と研究者
捜査官
- 主任研究者:John F. DiPersio, M.D., Ph.D.、Washington Univerisity School of Medicine
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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