Blinatumomab, Inotuzumab Ozogamicin, and Combination Chemotherapy as Frontline Therapy in Treating Patients With B Acute Lymphoblastic Leukemia
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| ClinicalTrials.gov Identifier: NCT02877303 |
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Recruitment Status :
Active, not recruiting
First Posted : August 24, 2016
Last Update Posted : May 13, 2024
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| 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 |
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 : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 80 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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, 2026 |
| Estimated Study Completion Date : | November 1, 2026 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Treatment (blinatumomab, inotuzumab, combination chemotherapy)
See detailed description.
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Biological: Blinatumomab
Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Cytarabine Given IT and IV
Other Names:
Drug: Dexamethasone Given PO
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Biological: Inotuzumab Ozogamicin Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Mercaptopurine Given PO
Other Names:
Drug: Methotrexate Given IT, IV, and PO
Other Names:
Biological: Ofatumumab Given IV
Other Names:
Drug: Prednisone Given PO
Other Names:
Biological: Rituximab Given IV
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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- 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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 14 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | 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
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
| United States, Texas | |
| M D Anderson Cancer Center | |
| Houston, Texas, United States, 77030 | |
| Principal Investigator: | Elias Jabbour | M.D. Anderson Cancer Center |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT02877303 |
| Other Study ID Numbers: |
2014-0845 NCI-2017-00596 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 2014-0845 ( Other Identifier: M D Anderson Cancer Center ) |
| First Posted: | August 24, 2016 Key Record Dates |
| Last Update Posted: | May 13, 2024 |
| Last Verified: | May 2024 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Neoplasms by Histologic Type Neoplasms Hematologic Diseases Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Cytarabine Dexamethasone Dexamethasone acetate Prednisone Cortisone |
Cyclophosphamide Rituximab Doxorubicin Liposomal doxorubicin Methotrexate Vincristine Mercaptopurine Ofatumumab Blinatumomab Inotuzumab Ozogamicin Antineoplastic Agents, Immunological Muromonab-CD3 Antibodies Immunoglobulins Antibodies, Monoclonal |