Clinical Trial 22318

• Overview

  Study Title:

  A Phase 1 Study of Avapritinib in Combination with Decitabine in Patients with Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN)

  Objective:

  PRIMARY OBJECTIVES To establish the recommended dose of avapritinib in combination with decitabine for further clinical evaluation of efficacy. SECONDARY OBJECTIVES To assess the efficacy of avapritinib in combination with decitabine in patients with SM-AHN. To characterize the safety profile of avapritinib in combination with decitabine in patients with SM-AHN.

• Treatments

  Therapies:

  Chemotherapy (NOS); Therapy (NOS)

  Medications:

  Avapritinib (); BLU-285 (Avapritinib); Cedazuridine (); decitabine (5-aza-2'-deoxycytidine)

• Inclusion Criteria

  Key Inclusion Criteria:
  • Diagnosis of SM-AHN defined by World Health Organization 2022 criteria.
  • ECOG 0-3
  • Ability to understand and the willingness to sign a written informed consent.
  • Ability to adhere to study visit schedule and other protocol requirements.
  • Willing to receive blood products as deemed clinically necessary.
  • Adequate organ and marrow function as defined by the protocol.
  • Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
  • For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
  • Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
  • Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should undergo a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.
  • Other Inclusion criteria may apply.

• Exclusion Criteria

  Key Exclusion Criteria:
  • History of decitabine use with documented disease progression of AHN by 2006 IWG MDS response criteria while on decitabine.
  • History of avapritinib use with documented progression of mastocytosis while on avapritinib per m-IWG-MRT-ECNM criteria.
  • History of treatment with decitabine in combination with avapritinib.
  • Use of a selective KIT inhibitor (other than avapritinib) within 4 weeks of first dose of study drug.
  • Use of azacitidine within 4 weeks of first dose of study drug.
  • Diagnosis of AML defined as presence of greater than or equal to 20% myeloblasts in the peripheral blood or bone marrow or presence of a myeloid sarcoma.
  • Patients who are receiving any other investigational agents or are participating in another interventional study.
  • Patient has a history of a seizure disorder (eg, epilepsy) or requirement for antiseizure medication.
  • Previous allogeneic hematopoietic stem cell transplant within 6 months prior to enrollment, active graft versus host disease (GVHD), or requiring transplant related immunosuppression.
  • Patients receiving any medications or substances that are strong or moderate CYP3A inhibitors or strong or moderate CYP3A inducers. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.
  • Participants with uncontrolled intercurrent illness.
  • Participants with psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study because, based on the mechanism of action and data from animal reproduction studies, in utero exposure to avapritinib may cause fetal harm.
  • Women who are breast feeding.
  • Patient is unwilling or unable to comply with scheduled visits, drug administration plan, laboratory tests, or other study procedures and study restrictions.
  • Patient has a primary brain malignancy or metastases to the brain.
  • Patient has had a major surgical procedure within 14 days of the first dose of study drug. Surgical procedures such as central venous catheter placement, bone marrow (BM) biopsy, and feeding tube placement are considered minor surgical procedures.
  • Patient has history of another primary malignancy that has been diagnosed or required therapy in the past year and/or is expected to require therapy in the next year. The following are exempt: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ of any site. Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
  • Patient is participating in another interventional clinical study.
  • Other exclusion criteria may apply.

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