Venetoclax, Dasatinib, Prednisone, Rituximab and Blinatumomab for the Treatment of Newly Diagnosed or Relapsed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia or Mixed Phenotype Acute Leukemia

NCT04872790 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: STUDY00022691NCI-2021-01791
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib trial studies the effects of venetoclax in combination with dasatinib, prednisone, rituximab and blinatumomab in treating patients with Philadelphia chromosome positive acute lymphoblastic leukemia (ALL) that is newly diagnosed or that has come back (relapsed). Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Anti-inflammatory drugs, such as prednisone lower the body's immune response and are used with other drugs in the treatment of some types of cancer. Rituximab and blinatumomab are monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving venetoclax in combination with dasatinib, prednisone, and rituximab and blinatumomab may help treat patients with newly diagnosed or relapsed Philadelphia chromosome positive acute lymphoblastic leukemia.

Conditions

B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1; B Acute Lymphoblastic Leukemia; Mixed Phenotype Acute Leukemia; Recurrent B Acute Lymphoblastic Leukemia; Recurrent Mixed Phenotype Acute Leukemia

Outcome Measures

Primary Outcomes (2)

• Incidence of dose-limiting toxicities

  A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications. In order to be declared a dose-limiting toxicity, an adverse experience must be determined related (definitely, probably, or possibly) to study drug. Point estimates and 95% exact confidence intervals will be reported for all patients in the safety set as well as in subgroups defined by whether or not a patient received blinatumomab consolidation therapy.

  At day 32 (after 30 days of combination therapy)

• Incidence of adverse events

  Adverse events will be graded and categorized according to the Common Terminology Criteria for Adverse Events version 5.0. Point estimates and 95% exact confidence intervals will be reported.

  Up to 90 days after last dose of study drug

Secondary Outcomes (4)

• Rate of complete molecular remission (CMR)

  Up to completion of cycle 3 (1 cycle = 28 days)

• Duration of complete molecular response (CMR)

  From date of CMR to date of molecular relapse, death or date of last follow-up, assessed up to 12 months after discontinuing study therapy

• Progression-free survival

  From first dose of dasatinib to relapse, disease progression, death, date of last follow-up, assessed up to 12 months after discontinuing study therapy

• Overall survival

  From first dose of dasatinib to death from any cause, assessed up to 12 months after discontinuing study therapy

Study Arms (1)

Treatment (prednisone, dasatinib, venetoclax, rituximab)

EXPERIMENTAL

See detailed description

Drug: Dasatinib; Drug: Methotrexate; Drug: Prednisone; Biological: Rituximab; Drug: Venetoclax; Biological: Blinatumomab; Procedure: Bone Marrow Aspiration and Biopsy; Procedure: Lumbar Puncture; Procedure: Biospecimen Collection

Interventions

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto, ABT 199, GDC0199

Treatment (prednisone, dasatinib, venetoclax, rituximab)

Blinatumomab BIOLOGICAL

Given IV

Also known as: 853426-35-4, AMG 103, Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody, Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103, Blincyto, MEDI-538, MEDI538, MT103, AMG-103, AMG103, MEDI 538, MT 103, MT-103

Treatment (prednisone, dasatinib, venetoclax, rituximab)

Bone Marrow Aspiration and Biopsy PROCEDURE

Undergo bone marrow aspiration and biopsy

Treatment (prednisone, dasatinib, venetoclax, rituximab)

Lumbar Puncture PROCEDURE

Undergo lumbar puncture

Also known as: LP, spinal tap

Treatment (prednisone, dasatinib, venetoclax, rituximab)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (prednisone, dasatinib, venetoclax, rituximab)

Dasatinib DRUG

Given PO

Also known as: BMS-354825, Dasatinib Hydrate, Dasatinib Monohydrate, Sprycel, BMS354825

Treatment (prednisone, dasatinib, venetoclax, rituximab)

Methotrexate DRUG

Given IT

Also known as: Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, CL 14377, CL-14377, Emtexate, Emthexat, Emthexate, Farmitrexat, Fauldexato, Folex, Folex PFS, Lantarel, Ledertrexate, Lumexon, Maxtrex, Medsatrexate, Metex, Methoblastin, Methotrexate LPF, Methotrexate Methylaminopterin, Methotrexatum, Metotrexato, Metrotex, Mexate, Mexate-AQ, MTX, Novatrex, Rheumatrex, Texate, Tremetex, Trexeron, Trixilem, WR-19039

Treatment (prednisone, dasatinib, venetoclax, rituximab)

Prednisone DRUG

Given PO

Also known as: .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Lisacort, Meprosona-F, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, Perrigo Prednisone, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisone Intensol, Prednisonum, Prednitone, Promifen, Rayos, Servisone, SK-Prednisone

Treatment (prednisone, dasatinib, venetoclax, rituximab)

Rituximab BIOLOGICAL

Given IV

Also known as: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Riabni, Rituxan, Rituximab ABBS, Rituximab ARRX, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar JHL1101, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, Rituximab Biosimilar SIBP-02, rituximab biosimilar TQB2303, Rituximab PVVR, rituximab-abbs, Rituximab-arrx, Rituximab-pvvr, RTXM83, Ruxience, Truxima, BI-695500, BI695500, Blitzima, IDEC 102, IDEC102, PF05280586, Ritemvia, Rituximab-rite, Rituximab-rixa, Rituximab-rixi, Rixathon, Riximyo, RTXM 83, RTXM-83

Treatment (prednisone, dasatinib, venetoclax, rituximab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have diagnosis of B acute lymphoblastic leukemia harboring the t(9;22) translocation (Philadelphia chromosome positive acute lymphoblastic leukemia \[Ph+ ALL\]) or Ph+ mixed phenotype acute leukemia (MPAL)) confirmed according to criteria.
• Diagnosis of MPAL will only be considered for enrollment during the dose finding period. Participants with MPAL will be enrolled for induction therapy only
• All individuals must have a bone marrow biopsy completed during the screening period. Patients with central nervous system (CNS) disease will be included
• Expression of CD19 by flow cytometry on bone marrow, if individual has received prior chimeric antigen receptor (CAR) T therapy. If CD19 negative, enrollment may be considered for induction treatment only
• Newly diagnosed subjects must have received no prior treatment for their ALL with the exception of steroids (prednisone, dexamethasone), hydrea or IT methotrexate. Individuals may receive pre-treatment with steroids during the screening phase prior to enrollment
• Individuals with relapsed disease may not have had prior treatment with dasatinib, however treatment with other tyrosine kinases is permitted
• At least 3 half-lives must have passed before cycle 1 day 1 (C1D1) for participants that have used strong CYP3A inhibitors (such as fluconazole, ketoconazole and clarithromycin) prior to enrollment
• At least 3 half-lives must have passed before cycle 1 day 3 (C1D3) for participants that have used moderate CYP3A inhibitors (such as fluconazole, ketoconazole and clarithromycin), strong or moderate CYP3A inducers (such as rifampin, carbamazepine, phenytoin, and St. John's wort), P-glycoprotein (P-gp) inhibitors, or warfarin prior to enrollment
• At least 4 weeks must have passed before (C1D3) for participants that have recently received a live vaccine
• Age \>= 18 years. All participants irrespective of their gender identity and members of all races and ethnic groups will be included
• Eastern Cooperative Oncology Group (ECOG) status =\< 2
• Must be able to take oral medication
• Aspartate aminotransferase (AST) \< 2.5 x upper limit of normal (ULN)
• Unless considered due to leukemic organ involvement
• Alanine aminotransferase (ALT) \< 2.5 x ULN

You may not qualify if:

• For newly diagnosed subjects: who have received treatment with cytotoxic chemotherapy, radiotherapy or immunotherapy for their ALL/MPAL, or prior dasatinib treatment. For relapsed subjects: prior dasatinib treatment (however treatment with other tyrosine kinase inhibitors \[TKIs\] is permitted)
• Subjects who have received any investigational agents or subjects who are taking investigational or commercial agents or therapies with the intent to treat the subject's malignancy within seven days or three half-lives of enrollment (i.e. initiation of dasatinib)
• Subjects with chronic myelogenous leukemia (CML) in myeloid blast crisis, Ph+ acute myeloid leukemia (AML) or acute leukemia lineage that cannot be classified based on existing criteria (e.g., from the World Health Organization \[WHO\] or International Consensus Classification \[ICC\])
• Subjects with clinically serious infections as determined by the provider requiring ongoing antibiotic therapy. This does not include antibiotic treatment for neutropenic fever
• Individuals with a pleural or pericardial effusion of any grade
• Subjects with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to dasatinib or other agents used in the study
• Subjects who have undergone stem cell transplant must be at least 100 days after transplant, and without active treatment for graft versus host disease (GVHD) other than topical medications
• Subjects with uncontrolled cardiac illness including but not limited to, symptomatic congestive heart failure, unstable angina pectoris, clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes), or pulmonary hypertension
• Subjects with diagnosed congenital prolonged QT syndrome
• Pregnant persons are excluded from this study because dasatinib is a pregnancy category D agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with dasatinib, breastfeeding should be discontinued if the mother is treated with dasatinib. These potential risks may also apply to venetoclax for which the pregnancy category and risks to the fetus are unknown
• Participant is seropositive with human immunodeficiency virus (HIV) or has active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
• HIV-infected individuals on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• For individuals with evidence of chronic HBV infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Individuals with a history of HCV infection must have been treated and cured. For individuals with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Subjects with invasive malignancy over the previous year except treated early stage carcinomas of the skin, completely resected intraepithelial carcinoma of the cervix, completely resected papillary thyroid and follicular thyroid cancers, and localized prostate cancer treated with curative intent with surgery or radiation

Sponsors & Collaborators

• Oregon Health and Science University: collaborator
• OHSU Knight Cancer Institute: lead
• AbbVie: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

Burkitt Lymphoma; Leukemia, Biphenotypic, Acute

Interventions

Dasatinib; Methotrexate; merphos; Prednisone; deltacortene; prednylidene; Rituximab; CT-P10; venetoclax; blinatumomab; N,N-dicyclohexyl-isoborneol-10-sulfonamide; Biopsy; Spinal Puncture; Specimen Handling

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Diagnostic Techniques, Neurological; Punctures; Therapeutics

Study Officials

• Jessica T Leonard

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 19, 2021
• First Posted: May 5, 2021
• Study Start: September 2, 2022
• Primary Completion (Estimated): December 2, 2027
• Study Completion (Estimated): December 2, 2027
• Last Updated: May 6, 2026

Record last verified: 2026-05

Locations

US (1)