- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03518112
Low-Intensity Chemotherapy and Blinatumomab in Treating Patients With Philadelphia Chromosome Negative Relapsed or Refractory Acute Lymphoblastic Leukemia
Phase II Study of the Combination of Low-Intensity Chemotherapy and Blinatumomab in Patients With Philadelphia Chromosome Negative Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVE:
I. To evaluate the combined effect of blinatumomab and mini-hyper-CVD (low-intensity chemotherapy) on event-free survival.
SECONDARY OBJECTIVES:
I. Evaluating other clinical efficacy endpoints (minimal residual disease [MRD] negativity, duration of response, the overall response rate [complete response (CR) + CR with inadequate count recovery (CRi)]) of the regimen occurred any time during the treatment.
II. Overall survival. III. Determining the safety of the combination regimen.
OUTLINE:
INDUCTION PHASE: Patients receive blinatumomab intravenously (IV) continuously on days 1-28 and dexamethasone orally (PO) or IV over 30 minutes on days -3 to day 0 and 7-10. Patients also receive filgrastim subcutaneously (SC) on days 1-42 or pegfilgrastim SC on days 1 and 25, cyclophosphamide IV over 3 hours twice daily (BID) on days -3 to -1, methotrexate intrathecally (IT) on day 2 and IV over 24 hours on day 22, cytarabine IT on day 7 and IV over 3 hours BID on days 23 and 24, and vincristine sulfate IV over 15 minutes on days 0 and 7. At the discretion of the treating physician, patients may receive rituximab IV over 4-6 hours on days -3, 0, 22 and 29, and leucovorin calcium IV over 15 minutes or PO 4 times daily (QID) for 8 doses.
CONSOLIDATION PHASE: Patients receive blinatumomab IV continuously on days 1-28 and dexamethasone PO or IV over 30 minutes on days 1-4 and 11-14. Patients also receive cyclophosphamide IV over 3 hours BID on days 1-3, vincristine sulfate IV over 15 minutes on days 1 and 11, filgrastim SC on days 1-4 and 22-42 or pegfilgrastim SC on day 5 and 25, methotrexate IT on day 2 and IV over 24 hours on day 22, cytarabine IT on day 7 and IV over 3 hours BID on days 23 and 24. At the discretion of the treating physician, patients may receive rituximab IV over 4-6 hours on days 1, 8, 22 and 29, and leucovorin calcium IV over 15 minutes or PO QID for 8 doses. Treatment repeats every 42 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE PHASE: Patients receive prednisone PO and vincristine sulfate IV over 15 minutes on days 1-5 of cycles 5-9, 7-11 and 13-24, and mercaptopurine PO BID on days 1-28 of cycles 1-5, 7-11, and 13-24. Patients also receive methotrexate PO once a week and blinatumomab IV continuously on days 1-28 of cycles 6 and 12. Cycles repeat every 28 days for up to 24 cycles (2 years) in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days.
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
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients with first or second relapsed/refractory B-cell acute lymphoblastic leukemia (ALL)
- Performance status =< 3 (Eastern Cooperative Oncology Group [ECOG] scale)
- Total serum bilirubin =< 2 x upper limit of normal (ULN), unless due to Gilbert's syndrome, hemolysis or the underlying leukemia approved by the principal investigator (PI)
- Alanine aminotransferase (ALT) =< 3 x ULN, unless due to the underlying leukemia approved by the PI
- Aspartate aminotransferase (AST) =< 3 x ULN unless due to the underlying leukemia approved by the PI
- Signed informed consent
- 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:
- Patients with Philadelphia chromosome (Ph)-positive ALL or Burkitt leukemia
- Active, uncontrolled central nervous system (CNS) leukemia involvement
- Active serious infection not controlled by oral or intravenous antibiotics
- Active secondary malignancy other than skin cancer (e.g., basal cell carcinoma or squamous cell carcinoma) that in the investigator's opinion will shorten survival to less than 1 year
- Known hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV)
- Active grade III-V cardiac failure as defined by the New York Heart Association criteria
- Patients with a cardiac ejection fraction (as measured by either multi-gated acquisition [MUGA] or echocardiogram) < 40%
- Prior history of treatment with blinatumomab
- Treatment with any investigational antileukemic agents or chemotherapy agents in the last two weeks, unless full recovery from side effects has occurred or patient has rapidly progressive disease judged to be life-threatening by the investigator
- Pregnant and lactating women will not be eligible; women of childbearing potential should have a negative pregnancy test prior to entering on the study and be willing to practice methods of contraception; women do not have childbearing potential if they have had a hysterectomy or are postmenopausal without menses for 12 months; in addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control
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, combination chemotherapy)
See detailed description.
|
Correlative studies
Given IV
Other Names:
Given PO
Other Names:
Given IV
Other Names:
Given SC
Other Names:
Given IV
Other Names:
Given SC
Other Names:
Given IV
Other Names:
Given IV
Other Names:
PO or IV
Other Names:
Given IT or IV
Other Names:
Given IT or IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Event Free Survival (EFS) Where Events Defined as no Response, Loss of Response, or Death
Time Frame: Time from the first day of treatment assessed up to 3 years, 1 month
|
Time from date of treatment start until the date of first objective documentation of disease-relapse. Relapse and resistant disease will be defined based on morphological assessment of bone marrow and peripheral blood. Complete Remission (CR): Normalization of the peripheral blood and bone marrow with 5% or less blasts in normocellular or hypercellular marrow with a granulocyte count of 1 x 10^9/L or above, and platelet count of 100 x 10^9/L. Complete resolution of all sites of extramedullary disease is required for CR. Complete remission without recovery of counts (CRi): Peripheral blood and marrow results as for CR, but with incomplete recover of counts (platelets < 100 x 10^9/L; neutrophils < 1 x 10^9/L). Partial Response (PR): As above for CR except for the presence of 6-25% marrow blasts. |
Time from the first day of treatment assessed up to 3 years, 1 month
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants Negative for Minimal Residual Disease (MRD)
Time Frame: Up to 3 years
|
Minimal Residual Disease (MRD) was assessed by flow cytometry.
MRD negativity: Absence of detectable leukemia using multiparameter flow cytometry with a sensitivity of </= 0.01%.
|
Up to 3 years
|
Duration of Response
Time Frame: Time from the first day of treatment assessed up to 3 years, 1 month
|
Response date to loss of response or last follow up. Complete Remission (CR): Normalization of the peripheral blood and bone marrow with 5% or less blasts in normocellular or hypercellular marrow with a granulocyte count of 1 x 10^9/L or above, and platelet count of 100 x 10^9/L. Complete resolution of all sites of extramedullary disease is required for CR. Complete remission without recovery of counts (CRi): Peripheral blood and marrow results as for CR, but with incomplete recover of counts (platelets < 100 x 10^9/L; neutrophils < 1 x 10^9/L). Partial Response (PR): As above for CR except for the presence of 6-25% marrow blasts. |
Time from the first day of treatment assessed up to 3 years, 1 month
|
Participants With a Response
Time Frame: Up to 3 years
|
defined as the percentage of patients achieving complete response (CR) or CR with inadequate count recovery (CRi). Complete Remission (CR): Normalization of the peripheral blood and bone marrow with 5% or less blasts in normocellular or hypercellular marrow with a granulocyte count of 1 x 10^9/L or above, and platelet count of 100 x 10^9/L. Complete resolution of all sites of extramedullary disease is required for CR. Complete remission without recovery of counts (CRi): Peripheral blood and marrow results as for CR, but with incomplete recover of counts (platelets < 100 x 10^9/L; neutrophils < 1 x 10^9/L). |
Up to 3 years
|
Overall Survival
Time Frame: Time from the first day of treatment assessed up to 3 years, 1 month
|
Time from date of treatment start until date of death due to any cause or last Follow-up.
|
Time from the first day of treatment assessed up to 3 years, 1 month
|
Collaborators and Investigators
Sponsor
Collaborators
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 (Actual)
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
- Dermatologic Agents
- Micronutrients
- Adjuvants, Immunologic
- 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
- Dexamethasone
- Dexamethasone acetate
- BB 1101
- Cyclophosphamide
- Antibodies
- Immunoglobulins
- Rituximab
- Leucovorin
- Calcium
- Levoleucovorin
- Lenograstim
- Antibodies, Monoclonal
- Antineoplastic Agents, Immunological
- Cytarabine
- Methotrexate
- Vincristine
- Mercaptopurine
- Folic Acid
- Calcium, Dietary
- Blinatumomab
- Muromonab-CD3
- Antibodies, Bispecific
Other Study ID Numbers
- 2017-0127 (Other Identifier: M D Anderson Cancer Center)
- NCI-2018-00737 (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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