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

University of Washington

Status and phase

Enrolling

Phase 2

Conditions

B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative

Treatments

Procedure: Computed Tomography

Procedure: Bone Marrow Biopsy

Biological: Rituximab

Drug: Vincristine

Drug: Etoposide

Procedure: Biospecimen Collection

Drug: Cyclophosphamide

Procedure: Lumbar Puncture

Drug: Prednisone

Drug: Doxorubicin

Procedure: Bone Marrow Aspiration

Biological: Tafasitamab

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT05453500

RG1122464

NCI-2022-05225 (Registry Identifier)

11008 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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).

Enrollment

30 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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)

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

30 participants in 1 patient group

Treatment (DA-EPOCH+/-R, tafasitamab)

Experimental group

Description:

Patients receive etoposide, doxorubicin, and vincristine IV continuously over 96 hours on days 1-4 of each cycle, cyclophosphamide IV over 1 hour on day 5 of each cycle, prednisone PO 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, CT scan, lumbar puncture and undergo blood sample and cerebrospinal fluid collection throughout the trial.

Treatment: