Clinical trial NCT05453500: Chemotherapy (DA-EPOCH+/-R) and Targeted Therapy (Tafasitamab) for the Treatment of Newly-Diagnosed Philadelphia Chromosome Negative B Acute Lymphoblastic Leukemia
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: Incyte Corporation
First posted: 2022-07-12
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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. Patients undergo bone marrow aspiration or biopsy, computed tomography (CT) scan, lumbar puncture and undergo blood sample and cerebrospinal fluid collection throughout the trial.

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).

Eligibility criteria: 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)

Primary outcomes:
measure: Rate of minimal residual disease (MRD)
timeFrame: After 1 cycle of treatment (each cycle = 21 days)
Secondary outcomes:
measure: Rate of MRD
timeFrame: After 4 cycles of treatment (each cycle = 21 days)
measure: Incidence of adverse events
timeFrame: Up to 5 years
measure: Event-free survival (EFS)
timeFrame: Up to 5 years
measure: Relapse-free survival (RFS)
timeFrame: Up to 5 years
measure: Overall survival (OS)
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutch/University of Washington Cancer Consortium
state: Washington
Study officials:
affiliation: Fred Hutch/University of Washington Cancer Consortium
name: Ryan D. Cassaday
role: PRINCIPAL_INVESTIGATOR
References: