A Phase 1/2 interventional study of LMB-2 and Fludarabine in Adult T-Cell Leukemia (ATL), sponsored by National Cancer Institute (NCI). Completed at 1 site in United States. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2023-11-14.
Sponsored by National Cancer Institute (NCI) · Phase 1/2, Interventional, and Treatment
BACKGROUND:
OBJECTIVES:
-To determine, in nonrandomized fashion, if after verifying its safety, fludarabine and cyclophosphamide (FC) prior to LMB2 for ATL can result in low immunogenicity and a rate of major response lasting greater than 2 months, which may be an improvement over that demonstrated previously from Alemtuzumab (CAMPATH).
Secondary objectives:
ELIGIBILITY:
DESIGN:
BACKGROUND:
OBJECTIVES:
Secondary objectives
ELIGIBILITY:
DESIGN:
31 studies on the registry are indexed under Leukemia-Lymphoma, Adult T-Cell; 5 are open to participants now.
This study's enrollment of 18 is below the median of 27 across 26 interventional studies indexed under Leukemia-Lymphoma, Adult T-Cell.
Browse Leukemia-Lymphoma, Adult T-Cell studies →National Cancer Institute (NCI) is the lead sponsor of 3,556 studies on the registry; 336 are open to participants now.
Of its 411 completed or terminated interventional studies of FDA-regulated products, 373 (91%) 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.
Diagnosis of acute or lymphomatous adult T-cell leukemia (ATL) by flow cytometry of blood or immunohistochemistry of tissue, confirmed by National Cancer Institute (NCI) Laboratory of Pathology, and previously treated unless the patient is ineligible for or refuses other protocols or treatments for ATL.
EXCLUSION CRITERIA:
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.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
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.
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.
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.
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.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
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 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.
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.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
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.
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.
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.
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.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
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 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.
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.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
FEV1
From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Administer cycle 1 with Fludarabine and Cyclophosphamide (FC) alone. Two weeks after starting cycle 1, begin up to 6 cycles of FC plus LMB-2 at minimum 20-day intervals.
Drug: LMB-2 · Drug: Fludarabine · Drug: Cyclophosphamide
Begin with 30 mcg/Kg intravenous (IV) on days 3, 5 and 7. Escalate to 40 mcg/Kg if dose limiting toxicity (DLT) in 0/3 or 1/6 at 30 mcg/Kg. Continue at 40 mcg/Kg if 0-1 of 6 have DLT at 40 mcg/Kg.
Days 1-3: Patients 1-7, 10-14, and \>18:25mg/m\^2/day Patients 8 - 9:30 mg/m\^2/day Patients 15- 17:20 mg/m\^2/day
Also known as: Fludara
Days 1-3: Patients 1-7, 10 -14, and \>18:250 mg/m\^2/day Patients 8 - 9:300 mg/m\^2/day Patients 15-17:200 mg/m\^2/day
Also known as: Cytoxan
Percentage of Participants With a Minimally Durable Clinical Response Rate
Response is based on the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphoma and must last \>8 weeks to meet the primary endpoint of the study. Complete remission (CR) is complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease related symptoms if present before therapy and normalization of those biochemical abnormalities definitely assignable to the lymphoma. Partial response is reduction by ≥50% of leukemia cell count or ≥50% reduction in the size of all measurable lesions, and no increase in size of any measurable or evaluable lesion or appearance of new lesion. Stable disease is neither a response nor progressive disease. Progressive disease is appearance of new lesions, or an increase of 50% or greater in the sum of the product of the perpendicular diameters of the measurable lesions or persistent (at least two determinations) doubling of the peripheral blood leukemic cell count.
Time frame: 8 weeks
Peak Level of LMB-2 in Adult T-Cell Lymphoma
The maximum analyte concentration in serum was reported using a cytotoxicity assay measuring the level of LMB-2 in the plasma and using purified LMB-2 as a standard curve.
Time frame: First 24 hours after the dose given on Cycle 2, day 1
Progression Free Survival (PFS)
PFS was determined by the Kaplan Meier method beginning at the on study date and continuing until progression or last follow-up without progression. Progressive disease is assessed by the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphoma, and is the appearance of new lesions, or an increase of 50% or greater in the sum of the product of the perpendicular diameters of the measurable lesions or persistent (at least two determinations) doubling of the peripheral blood leukemic cell count.
Time frame: 70 months
Overall Survival (OS)
OS is the time between the first day of treatment to the day of disease progression. Progressive disease is assessed by the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphoma, and is the appearance of new lesions, or an increase of 50% or greater in the sum of the product of the perpendicular diameters of the measurable lesions or persistent (at least two determinations) doubling of the peripheral blood leukemic cell count.
Time frame: 70 months
Number of Participants With Serious and Non-serious Adverse Events
Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time frame: 7 years and 12 days
Number of Participants With Dose Limiting Toxicity (DLT)
DLT is a grade II-IV LMB-2 or fludarabine and cyclophosphamide (FC)-related toxicity, except vascular leak syndrome, alopecia, grade II-III allergic reaction with asymptomatic bronchospasm or urticarial is considered DLT. Grade III aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, and fever are not considered DLT. Grade IV creatine phosphokinase associated with any other DLT or not resolving to \<grade II within 2 weeks is considered DLT. Hematologic toxicity is not considered DLT unless it fails to resolve to \<grade 2 or baseline by day 18 after cycle 1 or after day 25 after cycles 2-7. DLT from hepatotoxicity, creatine phosphokinase, and vascular leak syndrome is assumed from LMB-2, and hematologic toxicity from fludarabine and cyclophosphamide. Grade III proteinuria lasting \<2 weeks after the last dose of LMB-2 is not considered DLT, and needs to resolve to grade 0-2 prior to retreatment.
Time frame: 30 days after last dose of LMB2
Soluble Cluster of Differentiation 25 (sCD25) Between Responders and Nonresponders
Tumor tissue, including lymph node or skin biopsies was examined and analysis performed by flow cytometry to determine the amount of cancer cells in the body by measuring proteins which fall off cancer cells and go into the blood.
Time frame: First 24 hours after the dose given on Cycle 2, day 1
Area Under the Plasma Concentration (AUC) - LMB2
AUC is a measure of the plasma concentration of drug over time. It is used to characterize drug absorption. Plasma levels were analyzed by cytotoxicity assay.
Time frame: First 24 hours after the dose given on Cycle 2, day 1
Post Treatment Effects of LMB-2 + Fludarabine and Cyclophosphamide (FC) on Normal B and T Cell Subsets by Flow Cytometry
Peripheral blood was obtained and analyzed by flow cytometry.
Time frame: First 24 hours after the dose given on Cycle 2, day 1
Percentage of Patients Who Developed Neutralizing Antibodies After One or More Cycles of LMB-2
Blood was drawn prior to each cycle of LMB-2 to determine if the level, \>75% neutralization of 1000ng/ml of LMB-2 of neutralizing antibodies is too high to give additional LMB-2. Analysis was performed by cytotoxicity assay.
Time frame: First 24 hours after the dose given on Cycle 2, day 1
Duration of Response (Complete Response + Partial Response)
Duration of response is defined as a response lasting for at least 4 weeks but \>8 weeks and is assessed by the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphoma. Complete remission (CR) is complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease related symptoms if present before therapy and normalization of those biochemical abnormalities definitely assignable to the lymphoma. Partial response is reduction by ≥50% of leukemia cell count or ≥50% reduction in the size of all measurable lesions, and no increase in size of any measurable or evaluable lesion or appearance of new lesion.
Time frame: 69 months
Plasma Clearance (CL) of LMB-2
Dilutions of patient plasma was tested by cytotoxicity assays to determine plasma clearance of LMB-2.The CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Time frame: First 24 hours after the dose given on Cycle 2, day 1
Volume of Distribution of LMB-2
Dilutions of patient plasma were tested by cytotoxicity assays to determine volume of distribution of LMB-2. Volume distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. This was measured during the first 24 hours after administration of the dose on cycle 2 day 1.
Time frame: 24 hours
Half Life (t1/2) of LMB-2
Dilutions of patient plasma was tested by cytotoxicity assays to determine half life. Plasma decay half-life is the time measured for the plasma concentration of the drug to decrease by one half.
Time frame: First 24 hours after the dose given on Cycle 2, day 1
Count of Participants With Grades 3-5 Adverse Events of > 1 Adult T-Cell Leukemia (ATL) Patients Treated With 20+200, 25+250, and 30+300 mg/m^2 LMB-2/Fludarabine and Cyclophosphamide
Adverse events is assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 3 (mild), Grade 4 (life threatening) and Grade 5 (death).
Time frame: 7 years and 12 days
Count of Participants With Adverse Events Attributed At Least Possibly to Patients Treated With Fludarabine and Cyclophosphamide Dose Levels 20+200, 25+250, and 30+300 mg/m^2
Adverse events is assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time frame: 7 years and 12 days
| Milestone | Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | All Other Patients |
|---|---|---|
| Started | 10 | 8 |
| Completed | 3 | 0 |
| Not completed | 7 | 8 |
| Withdrew: Refused further treatment | 0 | 1 |
| Withdrew: Physician decision | 0 | 1 |
| Withdrew: Progressive disease | 3 | 6 |
| Withdrew: Stopped due to neutralizing antibodies | 3 | 0 |
| Withdrew: Death | 1 | 0 |
Response is based on the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphoma and must last \>8 weeks to meet the primary endpoint of the study. Complete remission (CR) is complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease related symptoms if present before therapy and normalization of those biochemical abnormalities definitely assignable to the lymphoma. Partial response is reduction by ≥50% of leukemia cell count or ≥50% reduction in the size of all measurable lesions, and no increase in size of any measurable or evaluable lesion or appearance of new lesion. Stable disease is neither a response nor progressive disease. Progressive disease is appearance of new lesions, or an increase of 50% or greater in the sum of the product of the perpendicular diameters of the measurable lesions or persistent (at least two determinations) doubling of the peripheral blood leukemic cell count.
| percentage of participants | Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | All Other Patients |
|---|---|---|
| Overall Response | 80 (44.4 to 97.5) | 0 (0 to 0) |
| Complete Response | 60 (26 to 88) | 0 (0 to 0) |
| Partial Response | 20 (2.5 to 55.6) | 0 (0 to 0) |
| Stable Disease | 20 (2.5 to 55.6) | 25 (3.2 to 65.1) |
| Progressive Disease | 0 (0 to 0) | 37.5 (8.5 to 75.5) |
| Not Evaluable | 0 (0 to 0) | 37.5 (8.5 to 75.5) |
The maximum analyte concentration in serum was reported using a cytotoxicity assay measuring the level of LMB-2 in the plasma and using purified LMB-2 as a standard curve.
| ng/mL | Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | All Other Patients |
|---|---|---|
| Peak Level of LMB-2 in Adult T-Cell Lymphoma | 602 (189 to 1072) | 484 (205 to 748) |
PFS was determined by the Kaplan Meier method beginning at the on study date and continuing until progression or last follow-up without progression. Progressive disease is assessed by the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphoma, and is the appearance of new lesions, or an increase of 50% or greater in the sum of the product of the perpendicular diameters of the measurable lesions or persistent (at least two determinations) doubling of the peripheral blood leukemic cell count.
| Months | Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | All Other Patients |
|---|---|---|
| Progression Free Survival (PFS) | 11.6 (1.5 to 25.2) | 1.05 (0.23 to 1.54) |
OS is the time between the first day of treatment to the day of disease progression. Progressive disease is assessed by the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphoma, and is the appearance of new lesions, or an increase of 50% or greater in the sum of the product of the perpendicular diameters of the measurable lesions or persistent (at least two determinations) doubling of the peripheral blood leukemic cell count.
| Months | Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | All Other Patients |
|---|---|---|
| Overall Survival (OS) | 18.6 (2.3 to 53.0) | 3.75 (1.3 to 16.0) |
Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
| Participants | Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | All Other Patients |
|---|---|---|
| Number of Participants With Serious and Non-serious Adverse Events | 10 | 8 |
DLT is a grade II-IV LMB-2 or fludarabine and cyclophosphamide (FC)-related toxicity, except vascular leak syndrome, alopecia, grade II-III allergic reaction with asymptomatic bronchospasm or urticarial is considered DLT. Grade III aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, and fever are not considered DLT. Grade IV creatine phosphokinase associated with any other DLT or not resolving to \<grade II within 2 weeks is considered DLT. Hematologic toxicity is not considered DLT unless it fails to resolve to \<grade 2 or baseline by day 18 after cycle 1 or after day 25 after cycles 2-7. DLT from hepatotoxicity, creatine phosphokinase, and vascular leak syndrome is assumed from LMB-2, and hematologic toxicity from fludarabine and cyclophosphamide. Grade III proteinuria lasting \<2 weeks after the last dose of LMB-2 is not considered DLT, and needs to resolve to grade 0-2 prior to retreatment.
| Participants | Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | All Other Patients |
|---|---|---|
| Number of Participants With Dose Limiting Toxicity (DLT) | 0 | 0 |
Tumor tissue, including lymph node or skin biopsies was examined and analysis performed by flow cytometry to determine the amount of cancer cells in the body by measuring proteins which fall off cancer cells and go into the blood.
| pg/ml | Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | All Other Patients |
|---|---|---|
| Soluble CD25, lowest post-treatment (nadir) value | 1094 (0 to 113000) | 34591 (5198 to 319000) |
| Median sCD25 Nadir for responders | 1082 (0 to 5999) | — |
| Median sCD25 Nadir for non-responders | 70713 (28425 to 113000) | 34591 (5198 to 319000) |
| Median sCD25 PRE-treatment for responders | 31893 (3163 to 190000) | — |
| Median sCD25 PRE-treatment for non-responders | 66419 (5838 to 127000) | 17079 (3668 to 122000) |
AUC is a measure of the plasma concentration of drug over time. It is used to characterize drug absorption. Plasma levels were analyzed by cytotoxicity assay.
| µg/-min/mL | Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | All Other Patients |
|---|---|---|
| Area Under the Plasma Concentration (AUC) - LMB2 | 161 (53.5 to 244) | 144 (49.8 to 205) |
Peripheral blood was obtained and analyzed by flow cytometry.
| Cells/µL | Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | All Other Patients |
|---|---|---|
| Normal T-cells | 28 (6 to 87) | 23.5 (1 to 156) |
| Normal CD4+ cells | 99.5 (4 to 427) | 186 (1 to 3818) |
| Normal CD8+ cells | 28 (6 to 87) | 23.5 (1 to 156) |
| Normal B-cells | 8 (0 to 119) | 0.5 (0 to 11) |
Blood was drawn prior to each cycle of LMB-2 to determine if the level, \>75% neutralization of 1000ng/ml of LMB-2 of neutralizing antibodies is too high to give additional LMB-2. Analysis was performed by cytotoxicity assay.
| percentage of participants | Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | All Other Patients |
|---|---|---|
| Percentage of Patients Who Developed Neutralizing Antibodies After One or More Cycles of LMB-2 | 40 (3.1 to 77) | 0 (0 to 0) |
Duration of response is defined as a response lasting for at least 4 weeks but \>8 weeks and is assessed by the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphoma. Complete remission (CR) is complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease related symptoms if present before therapy and normalization of those biochemical abnormalities definitely assignable to the lymphoma. Partial response is reduction by ≥50% of leukemia cell count or ≥50% reduction in the size of all measurable lesions, and no increase in size of any measurable or evaluable lesion or appearance of new lesion.
| Weeks | Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | All Other Patients |
|---|---|---|
| Duration of Response (Complete Response + Partial Response) | 69.6 (8 to 263) | 0 (0 to 0) |
Dilutions of patient plasma was tested by cytotoxicity assays to determine plasma clearance of LMB-2.The CL is a quantitative measure of the rate at which a drug substance is removed from the body.
| mL/min | Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | All Other Patients |
|---|---|---|
| Plasma Clearance (CL) of LMB-2 | 109 (10.9 to 134) | 101 (13.5 to 191) |
Dilutions of patient plasma were tested by cytotoxicity assays to determine volume of distribution of LMB-2. Volume distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. This was measured during the first 24 hours after administration of the dose on cycle 2 day 1.
| Liters | Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | All Other Patients |
|---|---|---|
| Volume of Distribution of LMB-2 | 49.6 (3.3 to 313) | 26.6 (4.89 to 133) |
Dilutions of patient plasma was tested by cytotoxicity assays to determine half life. Plasma decay half-life is the time measured for the plasma concentration of the drug to decrease by one half.
| min | Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | All Other Patients |
|---|---|---|
| Half Life (t1/2) of LMB-2 | 360 (105 to 542) | 251 (91.1 to 484) |
Adverse events is assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 3 (mild), Grade 4 (life threatening) and Grade 5 (death).
| Participants | Fludarabine and Cyclophosphamide: 20 + 200mg/m^2 | Fludarabine and Cyclophosphamide: 25 + 250mg/m^2 | Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 |
|---|---|---|---|
| Neutropenia | 2 | 10 | 2 |
| Nausea/vomiting/anorexia | 2 | 10 | 2 |
| Fever/chills | 1 | 10 | 1 |
| Leukopenia/lymphopenia | 1 | 9 | 2 |
| Transaminases | 3 | 8 | 1 |
| Hypotension/tachycardia | 1 | 8 | 2 |
| Thrombocytopenia | 1 | 8 | 2 |
| Anemia | 0 | 9 | 1 |
| Myalgia/headache | 2 | 7 | 2 |
| Hypoalbuminemia | 2 | 6 | 1 |
| Hematuria | 1 | 5 | 1 |
| Proteinuria | 0 | 7 | 0 |
| Fatigue/dizziness | 1 | 4 | 2 |
| Edema | 0 | 6 | 0 |
| Abdominal pain | 0 | 5 | 0 |
| Diarrhea | 1 | 3 | 0 |
| Creatine phosphokinase (CPK) | 0 | 4 | 0 |
| Mucositis | 0 | 3 | 1 |
| Hypomagnesemia | 0 | 3 | 0 |
| Bilirubin | 1 | 2 | 0 |
| Alkaline phosphatase/gamma-glutamyl transferase | 0 | 3 | 0 |
| Pneumonitis | 0 | 3 | 0 |
| Low cluster of differentiation 4 (CD4) count | 1 | 1 | 1 |
| Lipase | 0 | 3 | 0 |
| Bladder infection | 0 | 2 | 0 |
| Dyspnea | 0 | 2 | 0 |
| Prothrombin time | 1 | 1 | 0 |
| Pruritis | 1 | 0 | 1 |
Adverse events is assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
| Participants | Fludarabine and Cyclophosphamide: 20 + 200mg/m^2 | Fludarabine and Cyclophosphamide: 25 + 250mg/m^2 | 3Fludarabine and Cyclophosphamide: 0 + 300mg/m^2 |
|---|---|---|---|
| Neutropenia | 1 | 9 | 2 |
| Leukopenia/lymphopenia | 1 | 9 | 2 |
| Anemia | 0 | 8 | 0 |
| Transaminases | 1 | 4 | 0 |
| Thrombocytopenia | 0 | 5 | 1 |
| Fever/chills | 0 | 3 | 1 |
| Pneumonitis | 0 | 3 | 0 |
| Low cluster of differentiation 4 (CD4) count | 1 | 1 | 1 |
| Hypotension/tachycardia | 0 | 2 | 0 |
| Rectal hemorrhage | 0 | 1 | 0 |
| Bilirubin | 0 | 1 | 0 |
| Dysuria | 0 | 1 | 0 |
| Bladder infection | 0 | 1 | 0 |
| Hypoxia | 0 | 1 | 0 |
| Proteinuria | 0 | 1 | 0 |
| Sepsis* | 0 | 1 | 0 |
Collected over 7 years and 12 days. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 8/10 (80%) | 7/10 (70%) | 10/10 (100%) |
| All Other Patients | 6/8 (75%) | 6/8 (75%) | 8/8 (100%) |
| Event | Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | All Other Patients |
|---|---|---|
| Death related to diseaseGeneral disorders | 7/10 | 6/8 |
| Depressed level of consciousnessNervous system disorders | 2/10 | 0/8 |
| DyspneaRespiratory, thoracic and mediastinal disorders | 2/10 | 0/8 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specifyNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/10 | 1/8 |
| AcidosisMetabolism and nutrition disorders | 1/10 | 0/8 |
| Acute kidney injuryRenal and urinary disorders | 1/10 | 0/8 |
| Cardiac arrestCardiac disorders | 1/10 | 0/8 |
| DehydrationMetabolism and nutrition disorders | 1/10 | 0/8 |
| DizzinessNervous system disorders | 1/10 | 0/8 |
| Edema limbsGeneral disorders | 1/10 | 0/8 |
| Event | Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | All Other Patients |
|---|---|---|
| FeverGeneral disorders | 10/10 | 7/8 |
| Platelet count decreasedInvestigations | 10/10 | 4/8 |
| HypotensionVascular disorders | 9/10 | 2/8 |
| Lymphocyte count decreasedInvestigations | 9/10 | 5/8 |
| Neutrophil count decreasedInvestigations | 9/10 | 5/8 |
| AnemiaBlood and lymphatic system disorders | 8/10 | 5/8 |
| HyponatremiaMetabolism and nutrition disorders | 8/10 | 4/8 |
| MyalgiaMusculoskeletal and connective tissue disorders | 8/10 | 1/8 |
| NauseaGastrointestinal disorders | 8/10 | 6/8 |
| White blood cell decreasedInvestigations | 8/10 | 0/8 |
| Age, Categorical(Participants) | Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | All Other Patients | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 9 | 8 | 17 |
| >=65 years | 1 | 0 | 1 |
| Age, Continuous(years) | Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | All Other Patients | Total |
|---|---|---|---|
| Mean | 42 ± 14.25 | 39.8 ± 10.77 | 40.9 ± 12.51 |
| Sex: Female, Male(Participants) | Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | All Other Patients | Total |
|---|---|---|---|
| Female | 7 | 5 | 12 |
| Male | 3 | 3 | 6 |
| Ethnicity (NIH/OMB)(Participants) | Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | All Other Patients | Total |
|---|---|---|---|
| Hispanic or Latino | 1 | 0 | 1 |
| Not Hispanic or Latino | 9 | 7 | 16 |
| Unknown or Not Reported | 0 | 1 | 1 |
| Race/Ethnicity, Customized(Participants) | Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | All Other Patients | Total |
|---|---|---|---|
| African American | 2 | 2 | 4 |
| Tabago, Black | 1 | 0 | 1 |
| Peruvian, Hispanic | 1 | 0 | 1 |
| American from Jamaica, Black | 1 | 0 | 1 |
| Jamaican, Black | 5 | 2 | 7 |
| Ethiopian, Black | 0 | 1 | 1 |
| Jamaican | 0 | 0 | 0 |
| Barbados, Black | 0 | 2 | 2 |
| American, from Ghana, Black | 0 | 1 | 1 |
| Region of Enrollment(Participants) | Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | All Other Patients | Total |
|---|---|---|---|
| United States | 10 | 8 | 18 |
| Prior Treatment(Participants) | Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | All Other Patients | Total |
|---|---|---|---|
| CHOP | 2 | 3 | 5 |
| EPOCH-C | 0 | 1 | 1 |
| C, ESHAP, PTX, Gem | 1 | 0 | 1 |
| Medi507, Ontak, HAT | 1 | 0 | 1 |
| CHOP, C | 2 | 0 | 2 |
| EPOCH-RS | 1 | 1 | 2 |
| None | 1 | 0 | 1 |
| Hydroxyurea | 1 | 1 | 2 |
| CHOP, Hydroxyurea | 1 | 0 | 1 |
| LSG-15, radiation | 0 | 1 | 1 |
| Type of Leukemia(Participants) | Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | All Other Patients | Total |
|---|---|---|---|
| Acute | 10 | 3 | 13 |
| Lymphoma | 0 | 4 | 4 |
5 further baseline measures are reported on the registry.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
Time frame: Clinical data available during the study and indefinitely.
Access criteria: Clinical data will be made available via subscription to Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).
This study is completed, as verified in Oct 2023. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: B3(Fv)-PE38KDEL recombinant immunotoxin · Fludarabine · Cyclophosphamide
Leukemia-Lymphoma, Adult T-Cell →
National Cancer Institute (NCI) →