Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma, Burkitt Lymphoma/Leukemia, or Double-Hit Lymphoma/Leukemia

Официальное название

Lead-In and Phase II Study of Clofarabine, Etoposide, Cyclophosphamide [CEC], Liposomal Vincristine (VCR), Dexamethasone and Bortezomib in Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) and Lymphoblastic Lymphoma (LL)

Обзор

This phase II trial studies the side effects and how well combination chemotherapy works in treating patients with acute lymphoblastic leukemia, lymphoblastic lymphoma, Burkitt lymphoma/leukemia, or double-hit lymphoma/leukemia that has come back or does not respond to treatment. Drugs used in chemotherapy, such as clofarabine, etoposide, cyclophosphamide, vincristine sulfate liposome, dexamethasone and bortezomib, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Подробное описание

PRIMARY OBJECTIVE:

I. To collect the safety/toxicity information and assess the initial efficacy information (objective overall response rate: complete response \[CR\]+ CR with incomplete platelet recovery \[CRp\]/CR with incomplete bone marrow recovery \[CRi\]) after treatment with clofarabine, etoposide, cyclophosphamide (CEC), vincristine sulfate liposome (liposomal vincristine) (VCR), dexamethasone and bortezomib in relapsed/refractory acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) including relapsed/refractory Philadelphia (Ph) positive B-ALL/LL or Burkitt's leukemia/lymphoma or double-hit leukemia/lymphoma.

SECONDARY OBJECTIVE:

I. To determine the CR duration, event free survival (EFS), and overall survival (OS) after treatment with CEC, liposomal VCR, dexamethasone and bortezomib in relapsed/refractory ALL or LL including relapsed/refractory Ph positive B-ALL/LL or Burkitt's leukemia/lymphoma or double-hit leukemia/lymphoma.

OUTLINE:

INDUCTION: Patients receive clofarabine intravenously (IV) over 1-2 hours on days 1-5, etoposide IV over 2 hours on days 1-5, cyclophosphamide IV over 1 hour on days 1-5, vincristine sulfate liposome IV over 1 hour on days 2 and 11, dexamethasone orally (PO) daily or IV over 15 minutes on days 1-5, bortezomib subcutaneously (SC) on days 1, 4, 8 and 11, ofatumumab or rituximab IV over 4-24 hours on days 2 and 11, and pegfilgrastim SC on day 6 in the absence of disease progression or unacceptable toxicity. Patients may receive 1 additional course of induction therapy depending on the disease response.

CONSOLIDATION THERAPY: Patients receive clofarabine IV over 1-2 hours on days 1-4, etoposide IV over 2 hours on days 1-4, cyclophosphamide IV over 1 hour on days 1-4, vincristine sulfate liposome IV over 1 hour on days 2 and 11, dexamethasone PO or IV over 15 minutes on days 1-5, bortezomib SC on days 1, 4, 8 and 11, pegfilgrastim SC on day 6. Treatment repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. Patients may receive ofatumumab or rituximab IV over 4-24 hours on days 2 and 11 for 4 courses.

Вмешательства

• Препарат Bortezomib
  Given SC
• Препарат Clofarabine
  Given IV
• Препарат Cyclophosphamide
  Given IV
• Препарат Dexamethasone
  Given IV or PO
• Препарат Etoposide
  Given IV
• Биопрепарат Ofatumumab
  Given IV
• Биопрепарат Pegfilgrastim
  Given SC
• Биопрепарат Rituximab
  Given IV
• Препарат Vincristine Sulfate Liposome
  Given IV

Первичные конечные точки

• Incidence of adverse events [Срок оценки: Up to 8 years]
• Overall response rate (ORR) (Phase II) [Срок оценки: Up to 8 years]

Вторичные конечные точки (2)

• Overall survival [Срок оценки: From initiation of treatment, assessed up to 8 years]
• Event free survival [Срок оценки: From the treatment start, assessed up to 8 years]

Критерии участия

Критерии включения

• Relapsed/refractory acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL):

• Relapsed and/or refractory Philadelphia negative acute lymphoblastic leukemia or lymphoblastic lymphoma (LL) (Lead-in and Phase II)
• Relapsed and/or refractory Philadelphia positive acute lymphoblastic leukemia, Burkitt leukemia/lymphoma or "double-hit" leukemia/lymphoma (phase II only)
• At least 21 days elapsed from prior systemic chemotherapy (at least 14 days elapsed from prior systemic chemotherapy in the setting of rapidly progressive disease without significant residual extramedullary toxicity). Hydroxyurea and dexamethasone permitted up to approximately 24 hours prior to the start of therapy. Interruption of tyrosine kinase inhibitor (TKI) not required in Ph positive ALL subset
• Age older than 15 years
• Eastern Cooperative Oncology Group (ECOG) performance status =< 3 (There may be certain patients with performance status \[PS\] 3 in the context of rapidly proliferative/refractory ALL who would benefit from this regimen. We don't want to exclude such patients who may derive benefit from this salvage regimen)
• Serum bilirubin =< 1.5 mg/dL
• Serum glutamate pyruvate transaminase (SGPT) =< 3 x upper limit normal (ULN), with exception for Gilbert's syndrome
• Estimated creatinine clearance or GFR (glomerular filtration rate) >= 50 mL/min
• Signed informed consent

Критерии исключения

• Active >= grade 3 peripheral neuropathy
• Active hepatic graft-versus-host disease
• Known positivity for hepatitis B or C
• Pregnancy
• Breast feeding

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• M D Anderson Cancer Center — Houston

Идентификаторы

NCT: NCT03136146 · 2016-0211 · NCI-2018-01198 · 2016-0211

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗