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

Phase 2

Recruiting

• Conditions: Recurrent Acute Lymphoblastic Leukemia; Recurrent High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Burkitt Leukemia; Recurrent Burkitt Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Refractory Burkitt Leukemia; Refractory Lymphoblastic Lymphoma; Refractory Acute Lymphoblastic Leukemia; Refractory Burkitt Lymphoma
• Interventions: Drug: Bortezomib; Drug: Clofarabine; Drug: Cyclophosphamide; Drug: Dexamethasone; Drug: Etoposide; Biological: Ofatumumab; Biological: Pegfilgrastim; Biological: Rituximab; Drug: Vincristine Sulfate Liposome

• Registration Number: NCT03136146
• Lead Sponsor: M.D. Anderson Cancer Center

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2017-04-27
• Study First Submitted QC: 2017-04-27
• Study First Posted: 2017-05-02
• Study Start: 2017-08-09
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-08
• Last Update Posted: 2025-04-10
• Primary Completion: 2025-08-01
• Study Completion: 2026-08-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 42

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (combination chemotherapy)	Ofatumumab	See detailed description
Treatment (combination chemotherapy)	Bortezomib	See detailed description
Treatment (combination chemotherapy)	Rituximab	See detailed description
Treatment (combination chemotherapy)	Vincristine Sulfate Liposome	See detailed description
Treatment (combination chemotherapy)	Cyclophosphamide	See detailed description
Treatment (combination chemotherapy)	Clofarabine	See detailed description
Treatment (combination chemotherapy)	Dexamethasone	See detailed description
Treatment (combination chemotherapy)	Etoposide	See detailed description
Treatment (combination chemotherapy)	Pegfilgrastim	See detailed description

Primary Outcome Measures

Name	Time	Method
Incidence of adverse events	Up to 8 years	The severity of the toxicities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events.
Overall response rate (ORR) (Phase II)	Up to 8 years	Will be estimated along with the exact 95% confidence interval.

Secondary Outcome Measures

Name	Time	Method
Overall survival	From initiation of treatment, assessed up to 8 years	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.
Event free survival	From the treatment start, assessed up to 8 years	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.

Trial Locations

Locations (1)

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States