Chemotherapy (DA-EPOCH+/-R) and Targeted Therapy (Tafasitamab) for the Treatment of Newly-Diagnosed Philadelphia Chromosome Negative B Acute Lymphoblastic Leukemia

B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative Clinical Trial

Official title:

Dose-Adjusted Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (DA-EPOCH) +/- Rituximab (R) + Tafasitamab-cxix for the Treatment of Newly-Diagnosed Adults With Philadelphia Chromosome-Negative (Ph-) B-cell Lymphoblastic Lymphoma/Leukemia (B-ALL)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05453500
• Other study ID #: RG1122464
• Secondary ID: NCI-2022-0522511
• Status: Recruiting
• Phase: Phase 2
• Start date: March 27, 2023
• Est. completion date: September 1, 2030

Study information

• Verified date: April 2024
• Source: University of Washington
• Contact: Allie Rasmussen
• Phone: 206-606-2446
• Email: allegr[@]uw.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II clinical trial tests a chemotherapy regimen (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin with or without rituximab [DA-EPOCH+/-R]) with the addition of targeted therapy (tafasitamab) for the treatment of patients with newly diagnosed Philadelphia chromosome negative (Ph-) B acute lymphoblastic leukemia (B-ALL). Chemotherapy drugs, such as those in EPOCH+/-R, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Tafasitamab is in a class of medications called monoclonal antibodies. It works by helping the body to slow or stop the growth of cancer cells. Adding tafasitamab to the DA-EPOCH+/-R regimen may work better than DA-EPOCH+/-R alone in treating newly diagnosed Ph- B-ALL.

Description:

OUTLINE: Patients receive etoposide, doxorubicin, and vincristine intravenously (IV) continuously over 96 hours on days 1-4 of each cycle, cyclophosphamide IV over 1 hour on day 5 of each cycle, prednisone orally (PO) twice daily (BID) on days 1-5 of each cycle, and tafasitamab IV weekly on days 1, 8, and 15 of each cycle. CD20 positive patients also receive rituximab IV per guidelines on days 1 or 5 of each cycle. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years and every 6 months for 3 years (total follow-up time 5 years).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: September 1, 2030
• Est. primary completion date: September 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adults (age 18 years and older) with newly-diagnosed CD19+ Ph- B-ALL
• In the opinion of the treating investigator, patients must be an unsuitable candidate for a pediatric-inspired regimen, reasons for which may include (but not be limited to) older age (e.g., >= 40 years), practical/logistical barriers to or toxicity concerns from administration of a pediatric-inspired regimen
• Marrow or blood involvement detectable by MFC
• Total bilirubin =< 2.0 x upper limit of normal (ULN) (unless attributed to Gilbert's disease or other causes of inherited indirect hyperbilirubinemia, at which point total bilirubin must be =< 4.0 x ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5.0 x institutional ULN. (Note: Patients with liver test abnormalities attributable to hepatic involvement by ALL will be permitted if the total bilirubin is =< 5.0 x ULN and ALT/AST are =< 8.0 x ULN)
• Calculated creatinine clearance of > 30 ml/min, as measured by the Modification of Diet in Renal Disease (MDRD) equation, will be eligible
• As patients with ALL frequently have cytopenias, no hematologic parameters will be required for enrollment or to receive the first cycle of treatment. However, adequate recovery of blood counts will be required to receive subsequent cycles
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. (Performance status of 3 will be allowed if poor performance status is thought to be directly secondary to ALL)
• Ability to give informed consent and comply with the protocol
• Anticipated survival of at least 3 months, independent of ALL

Exclusion Criteria:

• Burkitt lymphoma/leukemia
• No prior systemic therapy for ALL except to control acute symptoms and/or hyperleukocytosis (e.g., corticosteroids, cytarabine, etc.)
• No isolated extramedullary or known parenchymal central nervous system (CNS) disease
• Known hypersensitivity or intolerance to any of the agents under investigation
• Other medical or psychiatric conditions that in the opinion of the investigator would preclude safe participation in the protocol
• May not be pregnant or nursing
• Pregnancy test is only required in women, unless they are highly unlikely to conceive (defined as [1] surgically sterilized, or [2] postmenopausal [i.e., a woman who is > 50 years old or who has not had menses for >=1 year], or [3] not heterosexually active)

Related Conditions & MeSH terms

• B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative
• Leukemia
• Leukemia, Lymphoid
• Philadelphia Chromosome
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Procedure:
• Bone Marrow Aspiration and Biopsy
Ancillary studies

Drug:
• Cyclophosphamide
Given IV
• Doxorubicin
Given IV
• Etoposide
Given IV
• Prednisone
Given PO

Biological:
• Rituximab
Given IV
• Tafasitamab
Given IV

Drug:
• Vincristine
Given IV

Locations

Country	Name	City	State
United States	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	Incyte Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of minimal residual disease (MRD)	Efficacy of the addition of tafasitamab (tafa) to dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin with our without rituximab (DA-EPOCH±R) will be assessed using the rate of minimal residual disease (MRD) as measured by multiparameter flow cytometry (MFC) in the University of Washington (UW) hematopathology lab. Will consider an absolute increase in the rate of MRD- after one cycle to 50% to be a signal of interest (i.e., increase from 28%).	After 1 cycle of treatment (each cycle = 21 days)
Secondary	Rate of MRD	Measured by MFC. Will be assessed only descriptively, using means and associated confidence intervals for continuous measures, simple ratios and Clopper-Pearson confidence intervals for binary measures, and either Kaplan-Meier or cumulative incidence estimates for time-to-event outcomes (depending on whether competing risks are present).	After 4 cycles of treatment (each cycle = 21 days)
Secondary	Incidence of adverse events	Safety measured by the incidence of non-hematologic toxicities >= grade 3 evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v) 5.0. Will be assessed only descriptively, using means and associated confidence intervals for continuous measures, simple ratios and Clopper-Pearson confidence intervals for binary measures, and either Kaplan-Meier or cumulative incidence estimates for time-to-event outcomes (depending on whether competing risks are present).	Up to 5 years
Secondary	Event-free survival (EFS)	Will be assessed only descriptively, using means and associated confidence intervals for continuous measures, simple ratios and Clopper-Pearson confidence intervals for binary measures, and either Kaplan-Meier or cumulative incidence estimates for time-to-event outcomes (depending on whether competing risks are present).	Up to 5 years
Secondary	Relapse-free survival (RFS)	Will be assessed only descriptively, using means and associated confidence intervals for continuous measures, simple ratios and Clopper-Pearson confidence intervals for binary measures, and either Kaplan-Meier or cumulative incidence estimates for time-to-event outcomes (depending on whether competing risks are present).	Up to 5 years
Secondary	Overall survival (OS)	Will be assessed only descriptively, using means and associated confidence intervals for continuous measures, simple ratios and Clopper-Pearson confidence intervals for binary measures, and either Kaplan-Meier or cumulative incidence estimates for time-to-event outcomes (depending on whether competing risks are present).	Up to 5 years