Clinical trial NCT03136146: Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma, Burkitt Lymphoma/Leukemia, or Double-Hit Lymphoma/Leukemia
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: 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
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2017-05-02
Enrollment: 42
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of adverse events
timeFrame: Up to 8 years
measure: Overall response rate (ORR) (Phase II)
timeFrame: Up to 8 years
Secondary outcomes:
measure: Overall survival
timeFrame: From initiation of treatment, assessed up to 8 years
measure: Event free survival
timeFrame: From the treatment start, assessed up to 8 years
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Maro Ohanian
role: PRINCIPAL_INVESTIGATOR
References: