Blinatumomab, Inotuzumab Ozogamicin, and Combination Chemotherapy as Frontline Therapy in Treating Patients With B Acute Lymphoblastic Leukemia
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02877303|
Recruitment Status : Recruiting
First Posted : August 24, 2016
Last Update Posted : February 23, 2021
|Condition or disease||Intervention/treatment||Phase|
|B Acute Lymphoblastic Leukemia B Lymphoblastic Lymphoma||Biological: Blinatumomab Drug: Cyclophosphamide Drug: Cytarabine Drug: Dexamethasone Drug: Doxorubicin Hydrochloride Biological: Inotuzumab Ozogamicin Other: Laboratory Biomarker Analysis Drug: Mercaptopurine Drug: Methotrexate Biological: Ofatumumab Drug: Prednisone Biological: Rituximab Drug: Vincristine Sulfate||Phase 2|
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).
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.
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.
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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||80 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||November 1, 2016|
|Estimated Primary Completion Date :||November 1, 2021|
|Estimated Study Completion Date :||November 1, 2021|
Experimental: Treatment (blinatumomab, inotuzumab, combination chemotherapy)
See detailed description.
Given IT and IV
Drug: Doxorubicin Hydrochloride
Biological: Inotuzumab Ozogamicin
Other: Laboratory Biomarker Analysis
Given IT, IV, and PO
Drug: Vincristine Sulfate
- 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.
- Overall survival [ Time Frame: Up to 24 months ]Will be estimated using the method of Kaplan and Meier.
- Overall response rate [ Time Frame: Up to 24 months ]Will be estimated along with the exact 95% confidence intervals.
- Minimal residual disease negativity rate [ Time Frame: Up to 24 months ]Will be estimated along with the exact 95% confidence intervals.
- Incidence of adverse events [ Time Frame: Up to 24 months ]Will be summarized by organ type, grade and attribution to study treatment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02877303
|Contact: Elias Jabbourfirstname.lastname@example.org|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Elias Jabbour 713-792-4764 email@example.com|
|Principal Investigator: Elias Jabbour|
|Principal Investigator:||Elias Jabbour||M.D. Anderson Cancer Center|