Inotuzumab Ozogamicin and Combination Chemotherapy in Treating Older Patients With Previously Untreated Acute Lymphoblastic Leukemia
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|ClinicalTrials.gov Identifier: NCT01371630|
Recruitment Status : Recruiting
First Posted : June 13, 2011
Last Update Posted : October 25, 2019
|Condition or disease||Intervention/treatment||Phase|
|Acute Lymphoblastic Leukemia B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative Untreated Adult Acute Lymphoblastic Leukemia||Biological: Blinatumomab Drug: Cyclophosphamide Drug: Cytarabine Biological: Inotuzumab Ozogamicin Other: Laboratory Biomarker Analysis Drug: Mercaptopurine Drug: Methotrexate Drug: Prednisone Biological: Rituximab Drug: Vincristine Sulfate||Phase 1 Phase 2|
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I. Determine the maximum tolerated dose (MTD) of inotuzumab ozogamicin in combination with low-intensity chemotherapy in elderly patients (age 60 or older) with acute lymphoblastic leukemia (ALL). (Phase I) II. Evaluate the efficacy of inotuzumab ozogamicin in combination with low-intensity chemotherapy in elderly patients with ALL. (Phase II) III. To evaluate the side effects of the treatment. (Phase II) IV. Evaluate the regimen efficacy in refractory-relapsed ALL. (Phase II)
I. To identify genomic alterations in adult ALL predictive for response and long-term outcomes with the combination of hyper-CVD (cyclophosphamide, dexamethasone, methotrexate, and cytarabine) + inotuzumab + blinatumomab.
II. To evaluate the impact of next generation sequencing (NGS)-based minimal residual disease (MRD) assay on outcomes and to compare with standard flow cytometry MRD assays.
OUTLINE: This is a phase I, dose-escalation study of inotuzumab ozogamicin followed by a phase II study.
CYCLES 1, 3, 7, AND 9: Patients receive cyclophosphamide intravenously (IV) over approximately 3 hours twice daily (BID) on days 1-3; vincristine sulfate IV over 30 minutes on days 1 and 8; inotuzumab ozogamicin IV over approximately 1 hour on day 3 of cycle 1 and day 2 or 3 of cycle 3; methotrexate intrathecally (IT) on day 2 of cycles 1 and 3; and cytarabine IT on day 8 of cycles 1 and 3. Patients may also receive rituximab IV on days 1 and 8 of cycles 1 and 3. Cycles alternate every 3-4 weeks in the absence of disease progression or unacceptable toxicity.
CYCLES 2, 4, 8, AND 10: Patients receive methotrexate IV over approximately 2 hours and then continuously over approximately 22 hours on day 1; cytarabine IV over approximately 3 hours BID on days 2-3; inotuzumab ozogamicin IV over approximately 1 hour on day 2 or 3 of cycles 2 and 4; cytarabine IT on day 5 of cycles 2 and 4; and methotrexate IT on day 8 of cycles 2 and 4. Patients may also receive rituximab IV on days 1 and 8 of cycles 2 and 4. Cycles alternate every 3-4 weeks in the absence of disease progression or unacceptable toxicity.
CYCLES 5, 6, 11, AND 12: Patients receive blinatumomab as a continuous intravenous infusion (CIVI) on days 1-29. Treatment repeats every 42 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Patients receive mercaptopurine orally (PO) BID and methotrexate PO once weekly for 3 years. Patients also receive vincristine sulfate IV over 30 minutes once monthly and prednisone PO daily five times a month for 1 year. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients who did not receive blinatumomab during induction and consolidation can receive 4 consecutive cycles of blinatumomab as in cycles 5, 6, 11, and 12, at any time during maintenance, after discussion with the principal investigator and if in the best interest of the patient.
TREATMENT OF MINIMAL RESIDUAL DISEASE (MRD): Patients with MRD may receive additional cycles of inotuzumab ozogamicin IV every 3-4 weeks for up to 6 doses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and every 4 months.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||256 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Study of the Combination of Inotuzumab Ozogamycin (CMC-544) With Low-Intensity Chemotherapy in Patients With Acute Lymphoblastic Leukemia (ALL)|
|Actual Study Start Date :||August 26, 2011|
|Estimated Primary Completion Date :||December 31, 2025|
|Estimated Study Completion Date :||December 31, 2025|
Experimental: Treatment (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description
Given IT and IV
Biological: Inotuzumab Ozogamicin
Other: Laboratory Biomarker Analysis
Given IT, IV, and PO
Drug: Vincristine Sulfate
- Maximum tolerated dose of inotuzumab ozogamicin based on incidence of dose limiting toxicities (Phase I) [ Time Frame: 28 days ]Defined as non-hematologic grade 3 or 4 toxicities during the first course. Toxicities will be monitored using the method of Thall, Simon, and Estey. Adverse events will be summarized and toxicity rate will be estimated with a 90% credible interval.
- Progression free survival (PFS) in frontline elderly acute lymphoblastic leukemia (ALL) (Phase II) [ Time Frame: 2 years ]Bayesian time-to-event model will be used. Kaplan and Meier product limit method will be used to estimate the PFS along with the 95% confidence intervals for the median PFS. Univariate and multivariate Cox proportional hazards regression models will be used to identify prognostic factors.
- Response rate in refractory-relapsed acute lymphoblastic leukemia (ALL) (Phase II) [ Time Frame: Up to 5 years ]The precise complete remission (CR) and marrow CR rate will be defined.
- Survival in refractory-relapsed acute lymphoblastic leukemia (ALL) (Phase II) [ Time Frame: Up to 1 year ]The median and 1-year survival rate will be defined. Kaplan and Meier product limit method will be used to estimate the overall survival (OS) along with the 95% confidence intervals for the median OS. Univariate and multivariate Cox proportional hazards regression models will be used to identify prognostic factors.
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): NCT01371630
|Contact: Elias Jabbouremail@example.com|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Elias Jabbour 713-792-7026|
|Principal Investigator: Elias Jabbour|
|Principal Investigator:||Elias Jabbour||M.D. Anderson Cancer Center|