- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03488225
Combination Chemotherapy and Inotuzumab Ozogamicin in Treating Patients With B Acute Lymphoblastic Leukemia
Phase II Study of the Hyper-CVAD Regimen in Sequential Combination With Inotuzumab Ozogamicin as Frontline Therapy for Adults With B-Cell Lineage Acute Lymphocytic Leukemia
Study Overview
Status
Conditions
Intervention / Treatment
- Other: Laboratory Biomarker Analysis
- Drug: Cyclophosphamide
- Drug: Mercaptopurine
- Drug: Prednisone
- Drug: Vincristine Sulfate
- Drug: Doxorubicin Hydrochloride
- Biological: Rituximab
- Biological: Inotuzumab Ozogamicin
- Drug: Leucovorin Calcium
- Biological: Ofatumumab
- Drug: Cytarabine
- Drug: Dexamethasone
- Drug: Methotrexate
Detailed Description
PRIMARY OBJECTIVES:
I. To evaluate the clinical efficacy of the sequential combination of hyper-CVAD (hyperfractionated cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, dexamethasone, methotrexate and cytarabine) + inotuzumab ozogamicin in patients with newly diagnosed B-cell acute lymphocytic leukemia (ALL) in terms of event-free survival (EFS).
SECONDARY OBJECTIVES:
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.
OUTLINE:
INTENSIVE CHEMOTHERAPY: Patients receive cyclophosphamide intravenously (IV) over 3 hours every 12 hours on days 1-3 and dexamethasone IV or orally (PO) on days 1-4 and 11-14 of courses 1 and 3. Patients may receive ofatumumab IV over 2 hours on days 1, 2 and 11 of course 1, days 1 and 8 of courses 2 and 4, and days 1 and 11 of course 3, or rituximab IV over 2 hours on days 1 and 11 of courses 1 and 3, and days 1 and 8 of courses 2 and 4. Patients also receive methotrexate intrathecally (IT) on day 2 of courses 1 and 3, IV over 24 hours on day 1 and IT on day 8 of courses 2 and 4, doxorubicin hydrochloride IV over 24 hours on day 4 of courses 1 and 3, vincristine sulfate IV over 1 hour on days 4 and 11 of courses 1 and 3, cytarabine IT on day 7 of courses 1 and 3, and IV over 2 hours every 12 hours on days 2 and 3, and IT on day 5 of courses 2 and 4, leucovorin calcium IV 4 times a days on day 2 of courses 2 and 4. Patients then receive inotuzumab ozogamicin IV over 1 hour on days 1 and 8 of courses 5-8. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Patients receive mercaptopurine PO thrice a day, methotrexate PO once a week, vincristine sulfate IV over 1 hour on day 1 and prednisone PO on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and every 6 months.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- M D Anderson Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Patients with newly diagnosed, previously untreated B-lineage ALL, or having achieved complete remission (CR) with one course of induction chemotherapy
- Patients with extramedullary disease only are eligible
- Failure to one induction course of chemotherapy (these patients will be analyzed separately)
- 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
- Women of childbearing potential (WOCBP) or male subjects with a partner who is WOCBP must agree to use contraception during the study, if sexually active
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
- 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 involvement or stable chronic liver disease per investigator assessment)
- Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active hepatitis C
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 (hyper-CVAD, inotuzumab ozogamicin)
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 IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IT or IV
Other Names:
Given IV or PO
Other Names:
Given IT, IV or PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Event-Free Survival
Time Frame: Start of treatment up to 2 years
|
Event-free survival defined as the time interval from date of treatment start until the date of death, disease progression or relapse.
|
Start of treatment up to 2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival
Time Frame: Start of treatment up to 2 years
|
Time from date of treatment start until date of death due to any cause or last Follow-up.
|
Start of treatment up to 2 years
|
Participants to Achieve Complete Remission (CR):
Time Frame: Start of treatment up to 2 years
|
Complete Remission (CR) is defined as - Normalization of the peripheral blood and bone marrow blasts </= 5% in normocellular or hypercellular marrow, granulocyte count of 1x10^9/L or above and platelets >/= 100X10^9/L and complete resolution of all sites of extramedullary disease.
|
Start of treatment up to 2 years
|
Number of Participants With Minimal Residual Disease (MRD) Negativity
Time Frame: Start of treatment up to 2 years
|
MRD levels continuously assessed during induction and consolidation therapy by 6-color multiparameter flow.
MRD negativity defined by a value of at least 10-4 and confirmed on a second bone marrow aspiration/biopsy performed after a subsequent cycle.
|
Start of treatment up to 2 years
|
Number of Participants With Adverse Events
Time Frame: Start of treatment up to 30 days after last dose received.
|
For the purpose of toxicity monitoring, toxicities are defined as any treatment -related grade 3 or 4 non-hematologic AEs occurred any time during the trial.NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 utilized for adverse event reporting.
|
Start of treatment up to 30 days after last dose received.
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Elias Jabbour, M.D. Anderson Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
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
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Chromosome Aberrations
- Translocation, Genetic
- Leukemia
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Leukemia, Lymphoid
- Philadelphia Chromosome
- 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
- Protective Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Dermatologic Agents
- Micronutrients
- Antibiotics, Antineoplastic
- Vitamins
- Bone Density Conservation Agents
- Calcium-Regulating Hormones and Agents
- Reproductive Control Agents
- Antidotes
- Vitamin B Complex
- Hematinics
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Immunoconjugates
- Immunotoxins
- Dexamethasone
- Dexamethasone acetate
- BB 1101
- Cyclophosphamide
- Antibodies
- Immunoglobulins
- Rituximab
- Leucovorin
- Calcium
- Levoleucovorin
- Ofatumumab
- Prednisone
- Doxorubicin
- Liposomal doxorubicin
- Antibodies, Monoclonal
- Antineoplastic Agents, Immunological
- Cytarabine
- Methotrexate
- Vincristine
- Mercaptopurine
- Folic Acid
- Calcium, Dietary
- Cortisone
- Inotuzumab Ozogamicin
Other Study ID Numbers
- 2015-0922 (Other Identifier: M D Anderson Cancer Center)
- P30CA016672 (U.S. NIH Grant/Contract)
- NCI-2018-00760 (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
product manufactured in and exported from the U.S.
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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