A Phase 3 interventional study of Blinatumomab and Dexamthasone in Acute Lymphoblastic Leukemia, sponsored by Amgen. Completed at 23 sites in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-02-08.
Sponsored by Amgen · Phase 3, Interventional, and Treatment
This study is being done to evaluate the rate of hematological response (complete remission/complete remission with partial hematological recovery [CR/CRh*]) induced by blinatumomab in Chinese adults with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL).
This is an open label, single-arm, multicenter phase 3 study to evaluate efficacy and safety of the BiTE (bispecific T cell engager) antibody blinatumomab in Chinese adults with relapsed/refractory B-precursor ALL. The study will consist of a screening period, a treatment period, and a follow-up period.
Treatment will consist of up to 5 cycles of blinatumomab. Participants who achieve a bone marrow (BM) response (≤ 5% BM blasts) or CR/CRh*/CRi within 2 induction cycles of treatment may continue to receive up to 3 additional consolidation cycles of blinatumomab. Thirty days after end of the last dose of protocol-specified therapy, participants will have a safety follow-up visit.
If subjects are suitable for allogeneic stem cell transplantation (alloHSCT) after treatment with blinatumomab, they may undergo alloHSCT instead of receiving further consolidation cycles with blinatumomab.
Participants will be followed via clinic visit or telephone contact every 3 months after their safety follow-up visit until death has been observed or a maximum of 2 years after start of treatment, whichever occurs first.
A planned interim analysis to assess efficacy and safety of blinatumomab was to be based on the interim analysis set (N = 90). The efficacious benefit assessment based on an O'Brien-Fleming alpha spending function (O'Brien and Fleming, 1979) with the critical boundary 42.2% at the interim analysis and 39.2% at the primary analysis in CR/CRh* rate. If the interim analysis showed statistically efficacious and overall benefit-risk analysis to be promising per the data review team review, then the interim analysis could become the primary analysis of this study. In addition, the study would continue its enrollment until 120 participants had been enrolled and continued their participation in the study to complete protocol-specified procedures.
The data cutoff date of 12 April 2019 allowed for the 90th participant enrolled before 21 February 2019 to have had the opportunity to complete 2 cycles of treatment and the safety follow-up visit (if the participant had discontinued treatment after 2 cycles).
2,584 studies on the registry are indexed under Precursor Cell Lymphoblastic Leukemia-Lymphoma; 473 are open to participants now.
This study's enrollment of 121 is above the median of 40 across 1,952 interventional studies indexed under Precursor Cell Lymphoblastic Leukemia-Lymphoma.
Browse Precursor Cell Lymphoblastic Leukemia-Lymphoma studies →Amgen is the lead sponsor of 1,047 studies on the registry; 52 are open to participants now.
Of its 246 completed or terminated interventional studies of FDA-regulated products, 166 (67%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Disease Related
Other Medical Conditions
Medications or Other Treatments
General
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Allogeneic and autologous transplant
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GVHD (graft-versus-host disease)
After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CTCAE grade
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Treatment consisted of two induction cycles and up to 3 consolidation cycles of treatment for responders. In the first induction cycle, the initial dose of blinatumomab was 9 μg/day for Days 1-7 and then escalated (dose step) to 28 μg/day starting on day 8 (week 2) through day 29 (week 4). This is followed by two weeks without blinatumomab treatment. In subsequent cycles (beginning with the second induction cycle and continuing through consolidation, for applicable participants) 28 μg/day was administered for all 4 weeks of continuous treatment, followed by a treatment-free interval of two weeks.
Drug: Blinatumomab · Drug: Dexamthasone
Blinatumomab will be supplied as single-use glass injection vials as a sterile, preservative-free, white to off-white, lyophilized powder for reconstitution and administration by continuous intravenous infusion (CIVI). A single cycle of blinatumomab treatment is 6 weeks in duration, which includes 4 weeks of blinatumomab CIVI followed by a 2 week treatment-free interval. The treatment-free interval may be prolonged by up to 7 days, if deemed necessary by the investigator.
Also known as: BLINCYTO®, AMG 103, MT103
Premedication with dexamethasone was intended to prevent cytokine release syndrome (CRS) events associated with blinatumomab treatment. Treatment could start pre-study. Dexamethasone 20 mg IV was administered within 3 hours before start of blinatumomab in each treatment cycle, and within 3 hours before dose step increase.
Percentage of Participants With a Hematological Response of Complete Remission (CR) or Complete Remission With Partial Hematological Recovery (CRh*) During the First 2 Treatment Cycles With Blinatumomab
A CR is defined as having ≤ 5% blasts in the bone marrow, no evidence of disease, and full recovery of peripheral blood counts (platelets \> 100,000/μL, and absolute neutrophil count \[ANC\] \> 1,000/μL). CRh\* is defined as ≤ 5% blasts in the bone marrow, no evidence of disease and partial recovery of peripheral blood counts: platelets \> 50,000/μl, and ANC \> 500/μl. CR/CRh\* rate is defined as the percentage of participants who achieve CR/CRh\* within 2 cycles of treatment with blinatumomab. Participants without response assessment were accounted for in the denominator when calculating the response rate, ie, these participants were counted as non-responders. The interim analysis was to become the primary analysis by meeting pre-specified efficacy and safety criteria based on an O'Brien-Fleming alpha spending function with the critical boundary 42.2%. Results for both the interim and final analysis are reported.
Time frame: Within 2 cycles of treatment (12 weeks)
Percentage of Participants With a Hematological Response of Complete Remission (CR) During the First 2 Treatment Cycles With Blinatumomab
A CR is defined as having ≤ 5% blasts in the bone marrow, no evidence of disease, and full recovery of peripheral blood counts (platelets \> 100,000/μL, and absolute neutrophil count \[ANC\] \> 1,000/μL). CR rate is defined as the percentage of participants who achieved CR within 2 cycles of treatment with blinatumomab. Participants without response assessment were accounted for in the denominator when calculating the response rate, ie, these participants were counted as non-responders. Results for both the interim and final analysis are reported.
Time frame: Within 2 cycles of treatment (12 weeks)
Percentage of Participants With a CR or CRh* or Complete Remission With Incomplete Hematological Recovery Without CRh* (CRi) (CR/CRh*/CRi) During the First 2 Treatment Cycles With Blinatumomab
CRi is defined as ≤ 5% blasts in the bone marrow, no evidence of disease and incomplete recovery of peripheral blood counts: platelets \> 100,000/μl or ANC \> 1,000/μl (but not both). CR/CRh\*/CRi rate is defined as the percentage of participants who achieve CR/CRh\*/CRi within 2 cycles of treatment with blinatumomab. Participants without response assessment were accounted for in the denominator when calculating the response rate, ie, these participants were counted as non-responders. Results for both the interim and final analysis are reported.
Time frame: Within 2 cycles of treatment (12 weeks)
Pharmacokinetic (PK) Parameter: Concentration of Blinatumomab at Steady State (Css)
Blinatumomab serum concentration was quantified using a validated enzyme- linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 pg/mL. Blinatumomab serum steady-state concentrations (Css) was summarized as the average of the observed concentrations collected after 24 hours from the start of continuous IV infusion for each dose level. Cycle 1 day 2 values represent Css for the initial dose of blinatumomab (9 µg/day). Values collected from other time points were used to calculate Css of 28 µg/day dose in their respective cycles.
Time frame: Cycle 1: Days 2, 15, and 29; Cycle 2: Days 2, 15, and 29 (approximately study days 44, 57, and 71)
Pharmacokinetic (PK) Parameter: Clearance
Systemic clearance (CL) calculated as the average CL value during cycle 1 and cycle 2, where CL = infusion rate (μg/hour) / Css
Time frame: Cycle 1: Days 2, 15 and 29; Cycle 2: Days 2, 15 and 29 (approximately study days 44, 57 and 71)
Pharmacokinetic (PK) Parameter: Terminal Half-Life
Terminal half-life (t1/2,z) calculated as t1/2,z = ln(2)/lambda-z, where lambda-z was the first-order rate constant estimated via linear regression of the terminal log-linear decay phase from day 29 post-end of infusion collections.
Time frame: Cycle 1 Day 29: prior to end of infusion and after the end of infusion at 3 hours and 6 hours
Pharmacokinetic (PK) Parameter: Volume of Distribution
The volume of distribution (Vz) was calculated as Vz = CL/lambda-z, where lambda-z was the first-order rate constant estimated based on cycle 1 day 29 collections via linear regression of the terminal log-linear decay phase as determined from the noncompartmental analysis and where CL was the CL averaged over multiple cycles. Volume of distribution was estimated for participants who have sufficient evaluable PK data.
Time frame: Cycle 1: Days 2, 15 and 29; Cycle 2: Days 2, 15, and 29 (approximately study days 44, 57 and 71)
Kaplan-Meier Estimates for Overall Survival (OS)
Overall survival time was calculated from the time of first infusion of blinatumomab until death due to any cause. Participants still alive were censored at the date last known to be alive up until the data cut-off date (interim analysis) or end of study date (final analysis). Months are calculated as days from the first treatment to death/censor date, divided by 30.5. Results for both the interim and final analysis are reported.
Time frame: Interim analysis: From first dose of blinatumomab to the data cutoff date of 12 April 2019; maximum time on follow-up for OS was 14.7 months. Final analysis: From first dose of blinatumomab to end of study; maximum time on follow-up for OS was 25.7 months
Kaplan-Meier Estimate for Relapse-Free Survival (RFS)
Relapse-free survival time was calculated from the first onset of CR/CRh\* within the first 2 cycles until the documented hematological relapse, extra-medullary disease, or death due to any cause, whichever occurred first. Participants who were still alive and relapse-free were censored at the date of last disease assessment. Months were calculated as days from the first onset of CR/CRh\* within the 2 cycles until the documented hematological relapse/extra-medullary disease/death/censor date, divided by 30.5. Results for both the interim and final analysis are reported.
Time frame: Interim Analysis: From first onset of CR/CRh* to the data cutoff date of 12 April 2019; maximum time on follow-up for RFS was 12.4 months. Final Analysis: From first onset of CR/CRh* to end of study; maximum time on follow-up for RFS was 18.1 months.
Percentage of Participants With Minimal Residual Disease (MRD) Response During the First Two Treatment Cycles
The detection of MRD (the presence of a low number of leukemic cells that are not detectable by light microscopy) after induction therapy and/or consolidation therapy is an independent prognostic factor for poor outcome of ALL. Participants highly responsive to chemotherapy with a MRD-level \< 1 × 10\^-4 leukemic cells detectable by flow cytometry induced by induction treatment, have a favorable prognosis. MRD response is defined as \< 1 ×10\^-4 leukemic cells detectable as measured by flow cytometry. MRD complete response is defined as having no detectable leukemic cells by flow cytometry. Results for both the interim and final analysis are reported.
Time frame: Within 2 cycles of treatment (12 weeks)
Percentage of Participants Who Received an Allogenic Hematopoietic Stem Cell Transplant (alloHSCT) After Achieving CR/CRh* During Treatment
Percentage of participants who underwent allogenic HSCT while in remission among those who responded to treatment by achieving CR/CRh\* during treatment. Results for both the interim and final analysis are reported.
Time frame: Interim analysis: Up to the data cutoff date of 12 April 2019; maximum time on follow-up was 14.7 months. Final analysis: Up to the end of study; maximum time on follow-up was 25.7 months.
100-Day Mortality After Allogeneic Hematopoietic Stem Cell Transplant
The 100-day mortality rate after allogeneic HSCT was defined as the percentage of participants having died up to 100 days after allogeneic HSCT estimated using the estimated time to death in percent calculated by Kaplan-Meier methods. Participants still alive alive were censored on the last documented visit date or the date of the last phone contact when the patient was last known to have been alive.
Time frame: 100 days after HSCT
Kaplan-Meier Estimates for Time to a ≥ Ten-Point Decrease From Baseline in Global Health Status Quality of Life
The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales, and 9 symptom scales/items. The GHS is reported in this outcome. For the GHS, scores range from 0 to 100 with a high score indicating better global health status/functioning. A ≥ 10-point decrease from baseline indicates a deterioration in quality of life. Months are calculated from start of blinatumomab date to deterioration/censor date, divided by 30.5.
Time frame: EORTC QLQ C30 was completed on days 1, 8, 15, and 29 during Cycle 1; days 1, 15, and 29 during cycle 2 and each consolidation cycle, and at the SFU visit (30 days after last dose).
Number of Participants With Treatment-Emergent Adverse Events (TEAE)
Adverse events (AEs) were evaluated for severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03, as follows: Grade 1 - Mild AE; Grade 2 - Moderate AE; Grade 3 - Severe AE; Grade 4 - Life-threatening or disabling AE; Grade 5 - Death. An AE was considered "serious" if it resulted in death, was life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant incapacity or substantial disruption to conduct normal life functions, was a congenital anomaly or birth defect or was a medically important condition.
Time frame: From day 1 to 30 days after last infusion of blinatumomab; median (min, max) treatment duration was 30.9 (1, 142) days.
Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (TEAE)
Adverse events (AEs) were evaluated for severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03, as follows: Grade 1 - Mild AE; Grade 2 - Moderate AE; Grade 3 - Severe AE; Grade 4 - Life-threatening or disabling AE; Grade 5 - Death. The investigator used medical judgment to determine if there was a causal relationship (ie, related, unrelated) between an adverse event and blinatumomab. An AE was considered "serious" if it resulted in death, was life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant incapacity or substantial disruption to conduct normal life functions, was a congenital anomaly or birth defect or was a medically important condition.
Time frame: From day 1 to 30 days after last infusion of blinatumomab; median (min, max) treatment duration was 30.9 (1, 142) days.
Participants With Anti-Blinatumomab Antibody Formation
Anti-blinatumomab binding antibodies were evaluated with a validated blinatumomab anti-drug antibody assay.
Time frame: Cycle 2, day 29 (after the completion of Cycle 2) and the SFU visit (30 days after last dose of blinatumomab)
This study was conducted at 23 centers in China. The study included a treatment period, a safety follow-up (SFU) visit 30 days after last dose and a follow-up period.
| Milestone | Blinatumomab |
|---|---|
| Started | 121 |
| Received blinatumomab | 120 |
| Interim analysis set | 90 |
| Completed | 23 |
| Not completed | 98 |
| Withdrew: Withdrawal by subject | 10 |
| Withdrew: Death | 80 |
| Withdrew: Lost to follow-up | 8 |
A CR is defined as having ≤ 5% blasts in the bone marrow, no evidence of disease, and full recovery of peripheral blood counts (platelets \> 100,000/μL, and absolute neutrophil count \[ANC\] \> 1,000/μL). CRh\* is defined as ≤ 5% blasts in the bone marrow, no evidence of disease and partial recovery of peripheral blood counts: platelets \> 50,000/μl, and ANC \> 500/μl. CR/CRh\* rate is defined as the percentage of participants who achieve CR/CRh\* within 2 cycles of treatment with blinatumomab. Participants without response assessment were accounted for in the denominator when calculating the response rate, ie, these participants were counted as non-responders. The interim analysis was to become the primary analysis by meeting pre-specified efficacy and safety criteria based on an O'Brien-Fleming alpha spending function with the critical boundary 42.2%. Results for both the interim and final analysis are reported.
| percentage of participants | Blinatumomab |
|---|---|
| Interim Analysis | 45.6 (35.0 to 56.4) |
| Final Analysis | 48.3 (39.1 to 57.6) |
A CR is defined as having ≤ 5% blasts in the bone marrow, no evidence of disease, and full recovery of peripheral blood counts (platelets \> 100,000/μL, and absolute neutrophil count \[ANC\] \> 1,000/μL). CR rate is defined as the percentage of participants who achieved CR within 2 cycles of treatment with blinatumomab. Participants without response assessment were accounted for in the denominator when calculating the response rate, ie, these participants were counted as non-responders. Results for both the interim and final analysis are reported.
| percentage of participants | Blinatumomab |
|---|---|
| Interim Analysis | 41.1 (30.8 to 52.0) |
| Final Analysis | 43.3 (34.3 to 52.7) |
CRi is defined as ≤ 5% blasts in the bone marrow, no evidence of disease and incomplete recovery of peripheral blood counts: platelets \> 100,000/μl or ANC \> 1,000/μl (but not both). CR/CRh\*/CRi rate is defined as the percentage of participants who achieve CR/CRh\*/CRi within 2 cycles of treatment with blinatumomab. Participants without response assessment were accounted for in the denominator when calculating the response rate, ie, these participants were counted as non-responders. Results for both the interim and final analysis are reported.
| percentage of participants | Blinatumomab |
|---|---|
| Interim Analysis | 47.8 (37.1 to 58.6) |
| Final Analysis | 50.0 (40.7 to 59.3) |
Blinatumomab serum concentration was quantified using a validated enzyme- linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 pg/mL. Blinatumomab serum steady-state concentrations (Css) was summarized as the average of the observed concentrations collected after 24 hours from the start of continuous IV infusion for each dose level. Cycle 1 day 2 values represent Css for the initial dose of blinatumomab (9 µg/day). Values collected from other time points were used to calculate Css of 28 µg/day dose in their respective cycles.
| pg/mL | Blinatumomab |
|---|---|
| Cycle 1: 9 μg/day | 103 ± 41 |
| Cycle 1: 28 μg/day | 416 ± 72 |
| Cycle 2: 28 μg/day | 634 ± 21 |
Systemic clearance (CL) calculated as the average CL value during cycle 1 and cycle 2, where CL = infusion rate (μg/hour) / Css
| L/hour | Blinatumomab |
|---|---|
| Pharmacokinetic (PK) Parameter: Clearance | 2.86 ± 57 |
Terminal half-life (t1/2,z) calculated as t1/2,z = ln(2)/lambda-z, where lambda-z was the first-order rate constant estimated via linear regression of the terminal log-linear decay phase from day 29 post-end of infusion collections.
| hours | Blinatumomab |
|---|---|
| Pharmacokinetic (PK) Parameter: Terminal Half-Life | 2.22 ± 31 |
The volume of distribution (Vz) was calculated as Vz = CL/lambda-z, where lambda-z was the first-order rate constant estimated based on cycle 1 day 29 collections via linear regression of the terminal log-linear decay phase as determined from the noncompartmental analysis and where CL was the CL averaged over multiple cycles. Volume of distribution was estimated for participants who have sufficient evaluable PK data.
| liters | Blinatumomab |
|---|---|
| Pharmacokinetic (PK) Parameter: Volume of Distribution | 7.15 ± 61 |
Overall survival time was calculated from the time of first infusion of blinatumomab until death due to any cause. Participants still alive were censored at the date last known to be alive up until the data cut-off date (interim analysis) or end of study date (final analysis). Months are calculated as days from the first treatment to death/censor date, divided by 30.5. Results for both the interim and final analysis are reported.
| months | Blinatumomab |
|---|---|
| Interim Analysis | 9.2 (6.5 to 11.7) |
| Final Analysis | 9.1 (7.2 to 11.7) |
Relapse-free survival time was calculated from the first onset of CR/CRh\* within the first 2 cycles until the documented hematological relapse, extra-medullary disease, or death due to any cause, whichever occurred first. Participants who were still alive and relapse-free were censored at the date of last disease assessment. Months were calculated as days from the first onset of CR/CRh\* within the 2 cycles until the documented hematological relapse/extra-medullary disease/death/censor date, divided by 30.5. Results for both the interim and final analysis are reported.
| months | Blinatumomab |
|---|---|
| Interim Analysis | 4.3 (3.2 to 9.4) |
| Final Analysis | 5.4 (3.9 to 6.1) |
The detection of MRD (the presence of a low number of leukemic cells that are not detectable by light microscopy) after induction therapy and/or consolidation therapy is an independent prognostic factor for poor outcome of ALL. Participants highly responsive to chemotherapy with a MRD-level \< 1 × 10\^-4 leukemic cells detectable by flow cytometry induced by induction treatment, have a favorable prognosis. MRD response is defined as \< 1 ×10\^-4 leukemic cells detectable as measured by flow cytometry. MRD complete response is defined as having no detectable leukemic cells by flow cytometry. Results for both the interim and final analysis are reported.
| percentage of participants | Blinatumomab |
|---|---|
| Interim Analysis: MRD Response | 82.9 (67.9 to 92.8) |
| Interim Analysis: MRD Complete Response | 2.4 (0.1 to 12.9) |
| Final Analysis: MRD Response | 84.5 (72.6 to 92.7) |
| Final Analysis: MRD Complete Response | 1.7 (0.0 to 9.2) |
Percentage of participants who underwent allogenic HSCT while in remission among those who responded to treatment by achieving CR/CRh\* during treatment. Results for both the interim and final analysis are reported.
| percentage of participants | Blinatumomab |
|---|---|
| Interim Analysis | 22.0 (10.6 to 37.6) |
| Final Analysis | 27.6 (16.7 to 40.9) |
The 100-day mortality rate after allogeneic HSCT was defined as the percentage of participants having died up to 100 days after allogeneic HSCT estimated using the estimated time to death in percent calculated by Kaplan-Meier methods. Participants still alive alive were censored on the last documented visit date or the date of the last phone contact when the patient was last known to have been alive.
| percentage of participants | Blinatumomab |
|---|---|
| Interim Analysis | 0.0 (NA to NA) |
| Final Analysis | 6.7 (1.0 to 38.7) |
The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales, and 9 symptom scales/items. The GHS is reported in this outcome. For the GHS, scores range from 0 to 100 with a high score indicating better global health status/functioning. A ≥ 10-point decrease from baseline indicates a deterioration in quality of life. Months are calculated from start of blinatumomab date to deterioration/censor date, divided by 30.5.
| months | Blinatumomab |
|---|---|
| Interim Analysis | 1.6 (1.0 to NA) |
| Final Analysis | 3.7 (1.1 to NA) |
Adverse events (AEs) were evaluated for severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03, as follows: Grade 1 - Mild AE; Grade 2 - Moderate AE; Grade 3 - Severe AE; Grade 4 - Life-threatening or disabling AE; Grade 5 - Death. An AE was considered "serious" if it resulted in death, was life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant incapacity or substantial disruption to conduct normal life functions, was a congenital anomaly or birth defect or was a medically important condition.
| Participants | Blinatumomab |
|---|---|
| Any TEAE | 120 |
| TEAE Grade ≥ 3 | 115 |
| Serious AE | 40 |
| TEAE leading to drug discontinuation | 18 |
| Serious AE leading to drug discontinuation | 12 |
| TEAE leading to drug interruption | 31 |
| Serious AE leading to drug interruption | 13 |
| Fatal AE | 11 |
Adverse events (AEs) were evaluated for severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03, as follows: Grade 1 - Mild AE; Grade 2 - Moderate AE; Grade 3 - Severe AE; Grade 4 - Life-threatening or disabling AE; Grade 5 - Death. The investigator used medical judgment to determine if there was a causal relationship (ie, related, unrelated) between an adverse event and blinatumomab. An AE was considered "serious" if it resulted in death, was life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant incapacity or substantial disruption to conduct normal life functions, was a congenital anomaly or birth defect or was a medically important condition.
| Participants | Blinatumomab |
|---|---|
| Any Treatment-related TEAE | 118 |
| Related TEAE Grade ≥ 3 | 99 |
| Related Serious AE (SAE) | 29 |
| Related TEAE leading to drug discontinuation | 16 |
| Related SAE leading to drug discontinuation | 11 |
| Related TEAE leading to drug interruption | 25 |
| Related SAE leading to drug interruption | 10 |
| Related fatal AE | 6 |
Anti-blinatumomab binding antibodies were evaluated with a validated blinatumomab anti-drug antibody assay.
| Participants | Blinatumomab |
|---|---|
| Binding antibody positive at anytime | 0 |
| Neutralizing antibody positive at anytime | 0 |
Collected over Mortality data are reported from enrollment to the end of study, maximum time on study was 26 months. Adverse events are reported from day 1 to 30 days after last infusion of blinatumomab; the median (min, max) treatment duration was 30.9 (1, 142) days.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Blinatumomab | 81/121 (66.9%) | 40/120 (33.3%) | 120/120 (100%) |
| Event | Blinatumomab |
|---|---|
| Cytokine release syndromeImmune system disorders | 5/120 |
| PneumoniaInfections and infestations | 5/120 |
| Liver injuryHepatobiliary disorders | 3/120 |
| Central nervous system leukaemiaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 3/120 |
| AnaemiaBlood and lymphatic system disorders | 2/120 |
| Respiratory tract infectionInfections and infestations | 2/120 |
| Platelet count decreasedInvestigations | 2/120 |
| Acute lymphocytic leukaemiaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 2/120 |
| Haemorrhage intracranialNervous system disorders | 2/120 |
| Disseminated intravascular coagulationBlood and lymphatic system disorders | 1/120 |
| Event | Blinatumomab |
|---|---|
| AnaemiaBlood and lymphatic system disorders | 76/120 |
| Cytokine release syndromeImmune system disorders | 71/120 |
| White blood cell count decreasedInvestigations | 65/120 |
| HypokalaemiaMetabolism and nutrition disorders | 62/120 |
| C-reactive protein increasedInvestigations | 60/120 |
| Neutrophil count decreasedInvestigations | 58/120 |
| PyrexiaGeneral disorders | 57/120 |
| Lymphocyte count decreasedInvestigations | 57/120 |
| Blood lactate dehydrogenase increasedInvestigations | 54/120 |
| Platelet count decreasedInvestigations | 53/120 |
Participants enrolled in the study who received at least 1 infusion of blinatumomab.
| Age, Continuous(years) | Blinatumomab |
|---|---|
| Mean | 35.4 ± 15.2 |
| Age, Customized(Participants) | Blinatumomab |
|---|---|
| < 35 years | 71 |
| ≥ 35 to < 55 years | 31 |
| ≥ 55 years | 18 |
| Age, Customized(Participants) | Blinatumomab |
|---|---|
| < 65 years | 115 |
| ≥ 65 to < 75 years | 5 |
| ≥ 75 years | 0 |
| Sex: Female, Male(Participants) | Blinatumomab |
|---|---|
| Female | 64 |
| Male | 56 |
| Race (NIH/OMB)(Participants) | Blinatumomab |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 120 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 0 |
| White | 0 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Age at Diagnosis(years) | Blinatumomab |
|---|---|
| Mean | 34.78 ± 15.1 |
| Eastern Cooperative Oncology Group (ECOG) Performance Scale(Participants) | Blinatumomab |
|---|---|
| Status 0 | 43 |
| Status 1 | 53 |
| Status 2 | 24 |
| Status > 2 | 0 |
| Key Entry Criterion(Participants) | Blinatumomab |
|---|---|
| Criteria #1 | 70 |
| Criteria #2 | 10 |
| Criteria #3 | 40 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report
Time frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
Data sharing details ↗ · www.amgen.com
Ran from Oct 2017 to primary completion in Aug 2019, 22 months.
Results were first posted in Sep 2020, 1 year after primary completion.
Of 59 phase 3 interventional studies under Precursor Cell Lymphoblastic Leukemia-Lymphoma, half reached primary completion within 86 months of starting (the median), counting those still running; a quarter within 46 and three quarters within 104. This study's 22 months is below that.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Feb 2023. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Blinatumomab
Precursor Cell Lymphoblastic Leukemia-Lymphoma →