A Study of Venetoclax in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Официальное название

A Phase 2 Open-Label Study of the Efficacy of Venetoclax in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Обзор

This is a Phase 2, open-label, multicenter study, evaluating the efficacy of venetoclax in participants with relapsed or refractory Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) either in presence of 17p deletion (Cohort 1) or those who have failed a B-receptor signaling pathway inhibitor (BCRI) therapy and who have also failed, or were unable to receive chemoimmunotherapy (CIT) irrespective of 17p status (Cohort 2).

Вмешательства

• Препарат Venetoclax
  Tablet; Oral

Первичные конечные точки

• Overall Response Rate (ORR) [Срок оценки: Measured up to 2 years after the last participant has enrolled in the study.]

Вторичные конечные точки (7)

• Complete Response Rate (CRR) [Срок оценки: Measured up to 2 years after the last participant has enrolled into the study.]
• Duration of Overall Response (DOR) [Срок оценки: Measured up to 2 years after the last participant has enrolled into the study.]
• Progression Free Survival (PFS) [Срок оценки: Measured up to 5 years after the last participant has enrolled into the study.]
• Event Free Survival (EFS) [Срок оценки: Measured up to 5 years after the last participant has enrolled into the study.]
• Time to Progression (TTP) [Срок оценки: Measured up to 5 years after the last participant has enrolled into the study.]
• Time to 50% reduction in absolute lymphocyte count (ALC) [Срок оценки: Measured up to 2 years after the last participant has enrolled into the study.]
• Overall Survival (OS) [Срок оценки: Measured up to 5 years after the last participant has enrolled into the study.]

Критерии участия

Критерии включения

• Participant must have a diagnosis of relapsed or refractory chronic lymphocytic leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) that meets 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (iwCLL) National Cancer Institute-Working Group (NCI-WG) Guidelines and the following:

• Participant must have an indication for treatment according to the 2008 Modified iwCLL NCI-WG Guidelines.
• SLL participant must have measurable disease (B-lymphocytosis greater than 5 × 10\^9/L or an enlarged lymph node(s) (Longest Diameter (LDi) > 1.5 cm at baseline) or hepatomegaly or splenomegaly due to CLL).
• SLL participant must have presence of lymphadenopathy and absence of cytopenias caused by a clonal marrow infiltrate.
• Participant must have relapsed or refractory CLL/SLL after receiving at least one prior line of therapy.
• Participants (in Cohort 1) must have 17p deletion, assessed by a central laboratory.
• Participants (in Cohort 2) must meet both of the following:

• Relapsed/refractory disease to B-Cell Receptor Signaling Pathway Inhibitor (BCRI) treatment;
• And either of the following: (a) relapsed/refractory disease to chemoimmunotherapy (CIT), or (b) ineligible to receive CIT, defined as having known 17p deletion or TP53 mutation, or Cumulative Illness Rating Scale (CIRS) >6 or calculated creatinine clearance <70 mL/min, or participants in whom the investigator evaluated that the use of CIT was inappropriate.
• Participant must have an Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to 2.
• Participant must have adequate bone marrow function, coagulation profile, renal, and hepatic function, per laboratory reference range at Screening.
• No known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Критерии исключения

• Participant has undergone an allogeneic stem cell transplant.
• Participant has developed Richter's transformation confirmed by biopsy.
• Participant has prolymphocytic leukemia.
• Participant has active and uncontrolled autoimmune cytopenias (for 2 weeks prior to screening), including autoimmune hemolytic anemia (AIHA) and idiopathic thrombocytopenic purpura (ITP).
• Participant has previously received venetoclax or other BCL-2 inhibitors.
• Participant is known to be positive for Human Immunodeficiency Virus (HIV).
• Participant has received a biologic agent for anti-neoplastic intent within 30 days prior to the first dose of study drug.
• Participant has received any of the following within 14 days or 5 half-lives (whichever is shorter) prior to the first dose of venetoclax, or has not recovered to less than Common Toxicity Criteria for Adverse Events (CTCAE) grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy:

• Any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy or targeted small molecule agents.
• Investigational therapy, including targeted small molecule agents.
• Participant has known allergy to both xanthine oxidase inhibitors and rasburicase.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 21 центр

• Anhui Provincial Cancer Hospital /ID# 209458 — Хэфэй
• Peking University People's Hospital /ID# 156575 — Пекин
• Peking Union Medical College Hospital (East) - Dongdan Campus /ID# 156576 — Пекин
• Fujian Medical University Union Hospital /ID# 156579 — Фучжоу
• Guangdong Provincial Peoples Hospital /ID# 160509 — Гуанчжоу
• Nanfang Hospital of Southern Medical University /ID# 156571 — Гуанчжоу
• The Second Hospital of Hebei Medical University /ID# 159143 — Shijiazhuang
• Henan Cancer Hospital /ID# 156573 — Чжэнчжоу
• … и ещё 13 центров

Тайвань · 5 центров

• National Taiwan University Hospital /ID# 210733 — Taipei City
• Changhua Christian Hospital /ID# 202768 — Changhua City, Changhua County
• Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 202765 — Kaohsiung City
• China Medical University Hospital /ID# 202767 — Taichung
• Linkou Chang Gung Memorial Hospital /ID# 203636 — Taoyuan City

Австралия · 3 центра

• Concord Repatriation General Hospital /ID# 201261 — Concord
• St George Hospital /ID# 206484 — Kogarah
• Monash Health - Monash Medical Centre /ID# 201263 — Clayton

Новая Зеландия · 2 центра

• North Shore Hospital /ID# 204637 — Takapuna
• Christchurch Hospital. /ID# 201650 — Christchurch

Идентификаторы

NCT: NCT02966756 · M14-728

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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