Phase II Study of the Hyper-CVAD Regimen in Sequential Combination With Blinatumomab With or Without Inotuzumab Ozogamicin as Frontline Therapy for Adults With B-Cell Lineage Acute Lymphocytic Leukemia
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 80
- Locations
- 2
- Primary Endpoint
- Relapse-free survival (RFS)
Study Overview
Brief Summary
This phase II trial studies how well blinatumomab, inotuzumab ozogamicin, and combination chemotherapy work as frontline therapy in treating patients with B acute lymphoblastic leukemia. Immunotherapy with monoclonal antibodies, such as blinatumomab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a toxic agent called ozogamicin. Inotuzumab attaches to CD22 positive cancer cells in a targeted way and delivers ozogamicin to kill them. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, dexamethasone, cytarabine, mercaptopurine, methotrexate, and prednisone 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. Giving blinatumomab, inotuzumab ozogamicin, and combination chemotherapy may work better in treating patients with B acute lymphoblastic leukemia than chemotherapy alone.
Detailed Description
PRIMARY OBJECTIVE:
I. To evaluate the clinical efficacy of the sequential combination of hyperfractionated cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone (hyper-CVAD) + blinatumomab + inotuzumab ozogamicin (inotuzumab) in patients with newly diagnosed B-cell acute lymphoblastic leukemia (ALL) in terms of relapse-free survival (RFS).
SECONDARY OBJECTIVE:
I. To evaluate other efficacy endpoints such as overall survival, overall response rate, minimal residual disease (MRD) negativity rate as well as the safety of this combination.
EXPLORATORY OBJECTIVES:
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 14 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients with newly diagnosed, previously untreated B-lineage ALL or lymphoblastic lymphoma, or having achieved complete remission (CR) with one course of induction chemotherapy; patients who require steroids, cytarabine (ara-c) or hydrea to manage disease symptoms prior to finalization of diagnosis and treatment plan are allowed and eligible
- •Failure to one induction course of chemotherapy (these patients will be analyzed separately); patients who require steroids, ara-c or hydrea to manage disease symptoms prior to finalization of diagnosis and treatment plan are allowed and eligible
- •Performance status of 0-3
- •Creatinine less than or equal to 2.0 mg/dL (unless considered tumor related)
- •Bilirubin less than or equal to 2.0 mg/dL (unless considered tumor related)
- •Adequate cardiac function as assessed by history and physical examination
- •No active or co-existing malignancy with life expectancy less than 12 months, sources for the determination of clinical significance by the treating physician will be included in the subject's medical record
Exclusion Criteria
- •Pregnant or nursing women
- •Known to be human immunodeficiency virus (HIV)-positive
- •Philadelphia chromosome (Ph)-positive ALL
- •Active and uncontrolled disease/infection as judged by the treating physician, sources for the determination of clinical significance by the treating physician will be included in the subject's medical record
- •Unable or unwilling to sign the consent form
- •Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per treating physician assessment), sources for the determination of clinical significance by the treating physician will be included in the subject's medical record
- •History or presence of clinically relevant central nervous system (CNS) pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis; (Patients with CNS involvement of leukemia are NOT excluded)
- •Current autoimmune disease or history of autoimmune disease with potential CNS involvement; auto-immune disease with possible CNS consequences/manifestations such as such as epilepsy, paresis, aphasia, stroke, dementia, Parkinson's disease, cerebellar disease, or psychosis
Arms & Interventions
Treatment (blinatumomab, inotuzumab, combination chemotherapy)
See detailed description.
Intervention: Prednisone (Drug)
Treatment (blinatumomab, inotuzumab, combination chemotherapy)
See detailed description.
Intervention: Rituximab (Biological)
Treatment (blinatumomab, inotuzumab, combination chemotherapy)
See detailed description.
Intervention: Vincristine Sulfate (Drug)
Treatment (blinatumomab, inotuzumab, combination chemotherapy)
See detailed description.
Intervention: Laboratory Biomarker Analysis (Other)
Treatment (blinatumomab, inotuzumab, combination chemotherapy)
See detailed description.
Intervention: Mercaptopurine (Drug)
Treatment (blinatumomab, inotuzumab, combination chemotherapy)
See detailed description.
Intervention: Methotrexate (Drug)
Treatment (blinatumomab, inotuzumab, combination chemotherapy)
See detailed description.
Intervention: Blinatumomab (Biological)
Treatment (blinatumomab, inotuzumab, combination chemotherapy)
See detailed description.
Intervention: Cyclophosphamide (Drug)
Treatment (blinatumomab, inotuzumab, combination chemotherapy)
See detailed description.
Intervention: Cytarabine (Drug)
Treatment (blinatumomab, inotuzumab, combination chemotherapy)
See detailed description.
Intervention: Dexamethasone (Drug)
Treatment (blinatumomab, inotuzumab, combination chemotherapy)
See detailed description.
Intervention: Doxorubicin Hydrochloride (Drug)
Treatment (blinatumomab, inotuzumab, combination chemotherapy)
See detailed description.
Intervention: Inotuzumab Ozogamicin (Biological)
Treatment (blinatumomab, inotuzumab, combination chemotherapy)
See detailed description.
Intervention: Ofatumumab (Biological)
Outcomes
Primary Outcomes
Relapse-free survival (RFS)
Time Frame: From date of treatment start until the date of death or disease relapse, assessed for up to 24 months
Will be estimated using the method of Kaplan and Meier. Will compute the Bayesian posterior probability. Will perform a competing risk analysis treating stem cell transplant as a competing event for RFS.
Secondary Outcomes
- Overall survival(Up to 24 months)
- Overall response rate(Up to 24 months)
- Minimal residual disease negativity rate(Up to 24 months)
- Incidence of adverse events(Up to 24 months)