Escalating Dose Study in Subjects With Relapsed or Refractory B Cell Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, and Waldenstrom's Macroglobulinemia

Celgene

Status and phase: Completed; Phase 1

Conditions: Waldenstrom Macroglobulinemia; Chronic Lymphocytic Leukemia; B Cell Non-Hodgkin's Lymphoma

Treatments: Drug: AVL-292

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01351935

AVL-292-003

Details and patient eligibility

About

The purpose of this study is to evaluate the safety and tolerability of AVL-292 as monotherapy in subjects with relapsed or refractory B cell non-Hodgkin lymphoma (B-NHL), chronic lymphocytic leukemia (CLL) or Waldenstrom's macroglobulinemia (WM).

Full description

Bruton's tyrosine kinase (Btk) is non-receptor tyrosine kinase with restricted cellular expression largely limited to B-lymphocytes, monocytes, and mast cells or basophils. Btk is a critical component of the B cell receptor (BCR) signaling network and is crucial for B cell development. Investigation has revealed that some B cell lymphomas and CLL depend on BCR signaling, suggesting that interruption of such signaling could be a promising therapeutic opportunity in B-NHL, CLL and WM.

Enrollment: 113 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Women and men ≥18 years of age

• Body weight ≥50 kg.

• Confirmed diagnosis of B cellNon-Hodgkin Lymphoma(according to World Health Organization [WHO] classification)including Chronic Lymphocytic Leukemia/Small cell Lymphocytic Leukemia (International Workshop),or Waldenstrom's Macroglobulinemia(Second International Workshop)

• Have failed ≥1 previous treatment for B-NHL/CLL/WM, and have relapsed or refractory disease following last prior treatment.

• Eastern Cooperative Oncology Group performance status of ≤ 2 and a life expectancy of at least 3 months.

• Ability to swallow oral capsules without difficulty

• Has recovered from adverse toxic effects of prior therapies

• Meet the following clinical laboratory requirements:

  • Creatinine ≤ 1.5 × upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 x ULN
  • AST and ALT ≤ 3 × ULN
  • Platelet count ≥ 50,000/µL (non-hodgkin & Waldenstrom's)
  • Platelet count ≥ 30,000/µL (chronic lymphocytic leukemia)
  • Absolute Neutrophil count ≥ 1000/µL

Exclusion criteria

• Prior allogeneic bone marrow transplant
• Autologous stem cell transplant within 3 months of screening
• Active central nervous system involvement
• Subjects with autoimmune hemolytic anemia or immune thrombocytopenia
• Prior treatment with a Btk inhibitor
• Active uncontrolled infection
• History of malabsorption
• Uncontrolled illness, i.e cardiac, endocrine, respiratory, etc.
• History of myocardial infarction, acute coronary syndromes, coronary angioplasty and/or stenting with in the previous 6 months
• History of another currently active cancer
• History of major surgery within 4 weeks or minor surgery within 1 week
• Other medical or psychiatric illness or organ dysfunction
• HIV positive
• Positive for Hepatitis B surface antigen or Hepatitis C-virus

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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113 participants in 1 patient group

AVL-292

Experimental group

Treatment:

Drug: AVL-292