- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02877303
Blinatumomab, Inotuzumab Ozogamicin, and Combination Chemotherapy as Frontline Therapy in Treating Patients With B Acute Lymphoblastic Leukemia
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
Study Overview
Status
Intervention / Treatment
- Other: Laboratory Biomarker Analysis
- Drug: Cyclophosphamide
- Drug: Mercaptopurine
- Drug: Prednisone
- Drug: Vincristine Sulfate
- Drug: Doxorubicin Hydrochloride
- Drug: Methotrexate
- Biological: Blinatumomab
- Biological: Rituximab
- Biological: Inotuzumab Ozogamicin
- Drug: Cytarabine
- Drug: Dexamethasone
- Biological: Ofatumumab
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:
I. To identify genomic alterations in adult ALL predictive for response and long-term outcomes with the combination of hyper-CVAD plus blinatumomab and inotuzumab.
II. To evaluate the impact of next generation sequencing (NGS)-based MRD assay on outcomes and to compare with standard flow cytometry MRD assays.
OUTLINE:
INTENSIVE PHASE: Patients receive cyclophosphamide intravenously (IV) over 3 hours twice daily (BID) on days 1-3, dexamethasone orally (PO) once daily (QD) on days 1-4 and 11-14, methotrexate intrathecally (IT) on day 2 of cycles 1 and 3, day 8 of cycles 2 and 4, and IV over 24 hours on day 1 of cycles 2 and 4, doxorubicin hydrochloride IV continuously on day 4, vincristine sulfate IV over 15 minutes on days 4 and 11, and cytarabine IT on day 7 of cycles 1 and 3, day 5 of cycles 2 and 4, and IV over 2 hours on days 2 and 3 of cycles 2 and 4. Patients may also receive ofatumumab IV or rituximab IV over 4-6 hours on days 1 and 11 of cycles 1 and 3, and days 1 and 8 of cycles 2 and 4 at the discretion of the treating physician. Patients may receive ofatumumab IV over 4-6 hours on day 2 of cycle 1. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
BLINATUMOMAB AND INOTUZUMAB OZOGAMICIN PHASE (CYCLES 5-8): Patients receive blinatumomab IV continuously on weeks 1-4. Patients also receive inotuzumab ozogamicin IV over 1 hour on days 5 and 11 of cycles 6 and 8. Treatment repeats every 6 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE PHASE: At doctor's discretion, patients may receive maintenance therapy prior to completing 4 cycles of hyper-CVAD and/or 4 cycles of blinatumomab. Patients receive mercaptopurine PO thrice daily (TID), methotrexate PO every week, vincristine sulfate IV over 15 minutes every month, and prednisone PO on days 1-5. Cycles repeat every 6 weeks for 12 months in the absence of disease progression or unacceptable toxicity. Patients also receive blinatumomab IV after every 3 cycles of maintenance therapy for a total of about 15 cycles.
After completion of study treatment, patients are followed up 1 time each month for up to 24 months.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Elias Jabbour
- Phone Number: 713-792-4764
- Email: ejabbour@mdanderson.org
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- Recruiting
- M D Anderson Cancer Center
-
Contact:
- Elias Jabbour
- Phone Number: 713-792-4764
- Email: ejabbour@mdanderson.org
-
Principal Investigator:
- Elias Jabbour
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (blinatumomab, inotuzumab, combination chemotherapy)
See detailed description.
|
Correlative studies
Given IV
Other Names:
Given PO
Other Names:
Given PO
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IT, IV, and PO
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IT and IV
Other Names:
Given PO
Other Names:
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
From date of treatment start until the date of death or disease relapse, assessed for up to 24 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival
Time Frame: Up to 24 months
|
Will be estimated using the method of Kaplan and Meier.
|
Up to 24 months
|
Overall response rate
Time Frame: Up to 24 months
|
Will be estimated along with the exact 95% confidence intervals.
|
Up to 24 months
|
Minimal residual disease negativity rate
Time Frame: Up to 24 months
|
Will be estimated along with the exact 95% confidence intervals.
|
Up to 24 months
|
Incidence of adverse events
Time Frame: Up to 24 months
|
Will be summarized by organ type, grade and attribution to study treatment.
|
Up to 24 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Elias Jabbour, M.D. Anderson Cancer Center
Publications and helpful links
General Publications
- Shi Z, Zhu Y, Zhang J, Chen B. Monoclonal antibodies: new chance in the management of B-cell acute lymphoblastic leukemia. Hematology. 2022 Dec;27(1):642-652. doi: 10.1080/16078454.2022.2074704.
- Jabbour E, Short NJ, Jain N, Thompson PA, Kadia TM, Ferrajoli A, Huang X, Yilmaz M, Alvarado Y, Patel KP, Garcia-Manero G, Macaron W, Garris R, Konopleva M, Ravandi F, Kantarjian H. Hyper-CVAD and sequential blinatumomab for newly diagnosed Philadelphia chromosome-negative B-cell acute lymphocytic leukaemia: a single-arm, single-centre, phase 2 trial. Lancet Haematol. 2022 Dec;9(12):e878-e885. doi: 10.1016/S2352-3026(22)00285-X. Epub 2022 Oct 22.
- Jabbour E, Kantarjian H. The Hyper-CVAD Regimen is an Optimal Pediatric-inspired Regimen for Adolescents and Adults With Acute Lymphoblastic Leukemia. Clin Lymphoma Myeloma Leuk. 2021 Jan;21(1):63-65. doi: 10.1016/j.clml.2020.09.001. Epub 2020 Oct 24. No abstract available.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Hematologic Diseases
- Leukemia
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Leukemia, Lymphoid
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Autonomic Agents
- Peripheral Nervous System Agents
- Antiviral Agents
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Protease Inhibitors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Dermatologic Agents
- Antibiotics, Antineoplastic
- Reproductive Control Agents
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Immunoconjugates
- Immunotoxins
- Dexamethasone
- Dexamethasone acetate
- BB 1101
- Cyclophosphamide
- Antibodies
- Immunoglobulins
- Rituximab
- Ofatumumab
- Prednisone
- Doxorubicin
- Liposomal doxorubicin
- Antibodies, Monoclonal
- Antineoplastic Agents, Immunological
- Cytarabine
- Methotrexate
- Vincristine
- Mercaptopurine
- Blinatumomab
- Cortisone
- Muromonab-CD3
- Antibodies, Bispecific
- Inotuzumab Ozogamicin
Other Study ID Numbers
- 2014-0845 (Other Identifier: M D Anderson Cancer Center)
- NCI-2017-00596 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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