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

Recurrent Adult Lymphoblastic Lymphoma Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03136146
• Other study ID #: 2016-0211
• Secondary ID: NCI-2018-0119820
• Status: Recruiting
• Phase: Phase 2
• Start date: August 9, 2017
• Est. completion date: August 1, 2026

Study information

• Verified date: March 2024
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: August 1, 2026
• Est. primary completion date: August 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• Active >= grade 3 peripheral neuropathy

• Active hepatic graft-versus-host disease

• Known positivity for hepatitis B or C

• Pregnancy

• Breast feeding

Related Conditions & MeSH terms

• Burkitt Lymphoma
• Leukemia
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Recurrence
• Recurrent Acute Lymphoblastic Leukemia
• Recurrent Adult Lymphoblastic Lymphoma
• Recurrent Burkitt Leukemia
• Recurrent Burkitt Lymphoma
• Recurrent Childhood Lymphoblastic Lymphoma
• Recurrent High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements
• Refractory Acute Lymphoblastic Leukemia
• Refractory Burkitt Leukemia
• Refractory Burkitt Lymphoma
• Refractory High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements
• Refractory Lymphoblastic Lymphoma

Intervention

Drug:
• Bortezomib
Given SC
• Clofarabine
Given IV
• Cyclophosphamide
Given IV
• Dexamethasone
Given IV or PO
• Etoposide
Given IV

Biological:
• Ofatumumab
Given IV
• Pegfilgrastim
Given SC
• Rituximab
Given IV

Drug:
• Vincristine Sulfate Liposome
Given IV

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events	The severity of the toxicities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events.	Up to 8 years
Primary	Overall response rate (ORR) (Phase II)	Will be estimated along with the exact 95% confidence interval.	Up to 8 years
Secondary	Overall survival	Will be estimated using the method of Kaplan and Meier. The log-rank tests will be used to compare the time-to-event outcomes among subgroups of patients.	From initiation of treatment, assessed up to 8 years
Secondary	Event free survival	Will be estimated using the method of Kaplan and Meier. The log-rank tests will be used to compare the time-to-event outcomes among subgroups of patients.	From the treatment start, assessed up to 8 years

External Links

•   MD Anderson Cancer Center