Adult T-Cell Leukemia (ATL)
Conditions
Keywords
Immunotoxin, CD25, Immunogenicity, Neutralization, Neutralizing Antibodies, Adult T-Cell Leukemia, Leukemia, ATL
Brief summary
BACKGROUND: * Cluster of differentiation 25 (CD25) (p55, Tac or interleukin 2 receptor (IL2R) alpha) is strongly expressed in virtually 100% of patients with adult T-cell leukemia/lymphoma (ATL), a highly aggressive human T-lymphotropic virus type 1 (HTLV-1) related malignancy responding poorly to chemotherapy. * In ATL, the humanized anti-CD25 monoclonal antibody (Mab) daclizumab produced 13-14% responses, and the anti-CD52 Mab Alemtuzumab (Campath-1H) produced response lasting greater than 2 months in 30% of 23 patients. * LMB-2 is an anti-CD25 recombinant immunotoxin containing variable domains of murine MAb anti-Tac and truncated Pseudomonas exotoxin. * In a phase I trial at National Cancer Institute (NCI), the maximum tolerated dose (MTD) of LMB-2 was 40 microg/Kg intravenous (IV) given every other day for 3 doses (every other day (QOD) times 3). LMB-2 induced greater than 90% tumor reduction rapidly in all 3 ATL patients on protocol, but achieved only 1 partial response due to rapid tumor progression and/or immunogenicity. * In preclinical models, response from recombinant immunotoxins is limited by high concentrations of soluble receptor in the blood and especially in the interstitial space of the tumor. Synergism was observed with chemotherapy and immunotoxins, possibly due to reduction of soluble receptor in tumor interstitium. 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: * To determine the effect of 1 cycle of FC alone in ATL. * To examine progression-free and overall survival in ATL after FC/LMB-2. * Evaluate pharmacokinetics, toxicity, and monitor soluble CD25 and other tumor marker levels in the serum. * To study the effects of LMB-2 plus FC on normal B- and T-cell subsets by fluorescence-activated cell sorting (FACS). ELIGIBILITY: * CD25 plus ATL, untreated or with prior therapy * Eastern Cooperative Oncology Group (ECOG) 0-2, absolute neutrophil count (ANC), platelets and albumin at least 1000, 75,000, and 3.0. DESIGN: * Fludarabine 25 mg/m(2) IV days 1-3 * Cyclophosphamide 250 mg/m(2) IV days 1-3 * LMB-2 30-40 micro g/Kg IV days 3, 5 and 7. * LMB-2 dose: Begin with 30 microg/Kg times 3. Escalate to 40 microg/Kg if dose limiting toxicity (DLT) in 0/3 or 1/6 at 30 microg/Kg. Continue at 40 microg/Kg if 0-1 of 6 have DLT at 40 microg/Kg. * Administer cycle 1 with FC alone. Two weeks after starting cycle 1, begin up to 6 cycles of FC plus LMB-2 at minimum 20-day intervals. * Accrual goals: 29-37 patients, which includes 4 replacements....
Detailed description
BACKGROUND: * Cluster of differentiation 25 (CD25) (p55, Tac or interleukin receptor 2 (IL2Ra) is strongly expressed in virtually 100 % of patients with adult T-cell leukemia/lymphoma (ATL), a highly aggressive human T-lymphotropic virus type 1 (HTLV-1) related malignancy responding poorly to chemotherapy. * In adult T-cell leukemia (ATL), the humanized anti-CD25 monoclonal antibody (Mab) daclizumab produced 13-14 % responses, and the anti-CD52 Mab Alemtuzumab (Campath- 1H) produced response lasting \> 8 weeks in of 30 % of 23 patients. * LMB-2 is an anti-CD25 recombinant immunotoxin containing variable domains of murine MAb anti-Tac and truncated Pseudomonas exotoxin. * In a phase I trial at National Cancer Institute (NCI), the maximum tolerated dose (MTD) of LMB-2 was 40 mcg/Kg dose intravenous (IV) given every other day for 3 doses (every other day (QOD) x3). LMB-2 induced \> 90 % tumor reduction rapidly in all 3 ATL patients on protocol, but achieved only 1 partial response due to rapid tumor progression and/or immunogenicity. * In preclinical models, response from recombinant immunotoxins is limited by high concentrations of soluble receptor in the blood and especially in the interstitial space of the tumor. Synergism was observed with chemotherapy and immunotoxins, possibly due reduction of soluble receptor in tumor interstitium. 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 \> 8 weeks which may be an improvement over that demonstrated previously from Alemtuzumab (CAMPATH). * Secondary objectives * To determine the effect of 1 cycle of FC alone in ATL. * To examine progression-free and overall survival in ATL after FC/LMB-2. * Evaluate pharmacokinetics, toxicity, and monitor soluble CD25 and other tumor marker levels in the serum. * To study the effects of LMB-2 +FC on normal B- and T-cell subsets by FACS. ELIGIBILITY: * CD25+ ATL, untreated or with prior therapy, leukemic type without malignant masses \> 4 cm. * Eastern Cooperative Oncology Group (ECOG) 0-2, absolute neutrophil count (ANC), platelets and albumin at least 1000, 75,000, and 3.0 respectively. DESIGN: * IV fludarabine and cyclophosphamide (FC) days 1-3 (doses listed respectively) * Patients 1-7 and 10-14, and \>18: 25 and 250 mg/m\^2/day * Patients 8-9: 30 and 300 mg/m\^2/day * Patients 15-17: 20 and 200 mg/m\^2/day * LMB-2 dose: Begin with 30 mcg/Kg 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. * Administer cycle 1 with FC alone. Two weeks after starting cycle 1, begin up to 6 cycles of FC plus LMB-2 at minimum 20 day intervals. * Accrual goals: 29-37 patients, which includes 4 replacements.
Interventions
DRUGLMB-2
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.
DRUGFludarabine
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
DRUGCyclophosphamide
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
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* INCLUSION CRITERIA: 1. Diagnosis of acute or lymphomatous adult T-cell leukemia (ATL) by flow cytometry of blood or immunohistochemistry of biopsy 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. 2. Neutralizing antibodies less than or equal to 75% neutralization of 200 ng/ml of LMB-2. 3. At least 18 years old. 4. Eastern Cooperative Oncology Group (ECOG) 0-2. 5. Able to understand and give informed consent. 6. Negative pregnancy test for females of childbearing potential. 7. The transaminases alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must each be less than or equal to 3-times the upper limits of normal (UNL) or less than or equal to 10-times normal if due to ATL. Albumin must be greater than or equal to 3.0 gm/dL. Total bilirubin must be less than or equal to 1.5 mg/dL except in patients with Gilberts syndrome (as defined by greater than 80 percent unconjugated bilirubin) it must be less than 5mg/dl. 8. Creatinine less than 2.0 mg/dL. 9. Absolute neutrophil count (ANC) greater than or equal to 1000/uL and platelets greater than or equal to 50,000/uL. 10. Current or prior features of acute ( corrected calcium (Ca)++ \> 2.73 or lactate dehydrogenase (LDH) 2- fold above ULN) or chronic (LDH 1.5-2-fold above ULN or absolute lymphocyte count \>4 x10\^9/L with T-cells \>3.5 x10\^9/L) ATL. Patients with smoldering ATL (no acute or chronic features) and symptomatic ATL skin lesions are also eligible.
Exclusion criteria
1. Prior therapy with LMB-2. 2. Central nervous system disease as evidenced by clinical symptomatology. 3. Cytotoxic chemotherapy, steroids or monoclonal antibody (Mab) within 3 weeks of enrollment, except anti Tac Mab (i.e. daclizumab), which cannot be used within 12 weeks of enrollment. Hydroxyurea is considered different from cytotoxic chemotherapy and may be used up to the day before enrollment providing it is not increased during the week prior to enrollment and that patients disease burden is not decreasing during that time. 4. Uncontrolled infection. 5. Untreated or uncontrolled 2nd malignancy. 6. Patients who are pregnant or breast-feeding. 7. Patients who have human immunodeficiency virus (HIV) or hepatitis C, since in these patients reductions in normal T- or B-cells would increase the risk of exacerbation of their underlying disease. Patients would not be excluded for hepatitis B surface antigen positivity if on Lamivudine or Entecavir. 8. Patients receiving warfarin (Coumadin \[R\]) 9. Patients with a left ventricular ejection fraction of less than 45%. 10. Patients with a diffusing capacity of the lungs for carbon monoxide (DLCO) less than 50% of normal or an forced expiratory volume 1 (FEV1) less than 50% of normal. 11. No concomitant use of alternative complimentary therapies or over the counter (OTC) agents allowed without prior approval of the principal investigator (PI). 12. Tumor or lymph node masses \> 4 cm.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Minimally Durable Clinical Response Rate | 8 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak Level of LMB-2 in Adult T-Cell Lymphoma | First 24 hours after the dose given on Cycle 2, day 1 | 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. |
| Progression Free Survival (PFS) | 70 months | 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. |
| Overall Survival (OS) | 70 months | 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. |
| Number of Participants With Serious and Non-serious Adverse Events | 7 years and 12 days | 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. |
| Number of Participants With Dose Limiting Toxicity (DLT) | 30 days after last dose of LMB2 | 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. |
| Soluble Cluster of Differentiation 25 (sCD25) Between Responders and Nonresponders | First 24 hours after the dose given on Cycle 2, day 1 | 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. |
| Area Under the Plasma Concentration (AUC) - LMB2 | First 24 hours after the dose given on Cycle 2, day 1 | 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. |
| Post Treatment Effects of LMB-2 + Fludarabine and Cyclophosphamide (FC) on Normal B and T Cell Subsets by Flow Cytometry | First 24 hours after the dose given on Cycle 2, day 1 | Peripheral blood was obtained and analyzed by flow cytometry. |
| Percentage of Patients Who Developed Neutralizing Antibodies After One or More Cycles of LMB-2 | First 24 hours after the dose given on Cycle 2, day 1 | 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. |
| Duration of Response (Complete Response + Partial Response) | 69 months | 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. |
| Plasma Clearance (CL) of LMB-2 | First 24 hours after the dose given on Cycle 2, day 1 | 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. |
| Volume of Distribution of LMB-2 | 24 hours | 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. |
| Half Life (t1/2) of LMB-2 | First 24 hours after the dose given on Cycle 2, day 1 | 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. |
| 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 | 7 years and 12 days | 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). |
| 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 | 7 years and 12 days | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC Leukemic patients receiving LMB-2 and at least 25+250 mg/m\^2 fludarabine and cyclophosphamide; CF03-CF05, CF07-CF10, and CF12-CF14. | 10 |
| All Other Patients Patients CF01-CF02, CF06, CF11, and CF15-CF18. This is a mixture of patients who did not receive LMB-2, who had lymphoma-type adult T-cell leukemia, and who received 20+250 mg/m\^2 of fludarabine cyclophosphamide (FC). | 8 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Progressive disease | 3 | 6 |
| Overall Study | Refused further treatment | 0 | 1 |
| Overall Study | Stopped due to neutralizing antibodies | 3 | 0 |
Baseline characteristics
| Characteristic | Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | All Other Patients | Total |
|---|---|---|---|
| Adult T-cell Leukemia (ATL) cells/mm^3 in the Peripheral Blood 0 cells | 0 Participants | 3 Participants | 3 Participants |
| Adult T-cell Leukemia (ATL) cells/mm^3 in the Peripheral Blood 13,153 cells | 1 Participants | 0 Participants | 1 Participants |
| Adult T-cell Leukemia (ATL) cells/mm^3 in the Peripheral Blood 1 cell | 0 Participants | 1 Participants | 1 Participants |
| Adult T-cell Leukemia (ATL) cells/mm^3 in the Peripheral Blood 206 cells | 1 Participants | 0 Participants | 1 Participants |
| Adult T-cell Leukemia (ATL) cells/mm^3 in the Peripheral Blood 210,000 cells | 1 Participants | 0 Participants | 1 Participants |
| Adult T-cell Leukemia (ATL) cells/mm^3 in the Peripheral Blood 213,000 cells | 0 Participants | 1 Participants | 1 Participants |
| Adult T-cell Leukemia (ATL) cells/mm^3 in the Peripheral Blood 24,112 cells | 1 Participants | 0 Participants | 1 Participants |
| Adult T-cell Leukemia (ATL) cells/mm^3 in the Peripheral Blood 246 cells | 1 Participants | 0 Participants | 1 Participants |
| Adult T-cell Leukemia (ATL) cells/mm^3 in the Peripheral Blood 408 cells | 1 Participants | 0 Participants | 1 Participants |
| Adult T-cell Leukemia (ATL) cells/mm^3 in the Peripheral Blood 450 cells | 0 Participants | 1 Participants | 1 Participants |
| Adult T-cell Leukemia (ATL) cells/mm^3 in the Peripheral Blood 5,604 cells | 1 Participants | 0 Participants | 1 Participants |
| Adult T-cell Leukemia (ATL) cells/mm^3 in the Peripheral Blood 687 cells | 1 Participants | 0 Participants | 1 Participants |
| Adult T-cell Leukemia (ATL) cells/mm^3 in the Peripheral Blood 7,737 cells | 0 Participants | 1 Participants | 1 Participants |
| Adult T-cell Leukemia (ATL) cells/mm^3 in the Peripheral Blood 80 cells | 1 Participants | 0 Participants | 1 Participants |
| Adult T-cell Leukemia (ATL) cells/mm^3 in the Peripheral Blood 8,216 cells | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 8 Participants | 17 Participants |
| Age, Continuous | 42 years STANDARD_DEVIATION 14.25 | 39.8 years STANDARD_DEVIATION 10.77 | 40.9 years STANDARD_DEVIATION 12.51 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 7 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Extravascular sites Bone, lung, skin | 0 Participants | 1 Participants | 1 Participants |
| Extravascular sites Bone, subcutaneous | 0 Participants | 1 Participants | 1 Participants |
| Extravascular sites Lymph node (LN) | 1 Participants | 2 Participants | 3 Participants |
| Extravascular sites Muscle | 1 Participants | 0 Participants | 1 Participants |
| Extravascular sites None | 1 Participants | 0 Participants | 1 Participants |
| Extravascular sites Pelvis | 1 Participants | 0 Participants | 1 Participants |
| Extravascular sites Skin | 1 Participants | 0 Participants | 1 Participants |
| Extravascular sites Spleen | 2 Participants | 0 Participants | 2 Participants |
| Extravascular sites Spleen, LN | 2 Participants | 1 Participants | 3 Participants |
| Extravascular sites Subcutaneous | 1 Participants | 1 Participants | 2 Participants |
| Extravascular sites Thigh (skin) | 0 Participants | 1 Participants | 1 Participants |
| Maximum tumor size 15, 2.5 cm tumor | 0 Participants | 1 Participants | 1 Participants |
| Maximum tumor size 17.5 cm tumor | 1 Participants | 0 Participants | 1 Participants |
| Maximum tumor size 17 cm tumor | 1 Participants | 0 Participants | 1 Participants |
| Maximum tumor size 18.5, 1.7 cm tumor | 1 Participants | 0 Participants | 1 Participants |
| Maximum tumor size 1.9 cm tumor | 0 Participants | 1 Participants | 1 Participants |
| Maximum tumor size <1 cm tumor | 4 Participants | 1 Participants | 5 Participants |
| Maximum tumor size 20, 1.8 cm tumor | 1 Participants | 0 Participants | 1 Participants |
| Maximum tumor size 2.2 cm tumor | 0 Participants | 1 Participants | 1 Participants |
| Maximum tumor size 2 cm tumor | 1 Participants | 0 Participants | 1 Participants |
| Maximum tumor size 5.6 cm tumor | 1 Participants | 0 Participants | 1 Participants |
| Maximum tumor size 5.8 cm tumor | 0 Participants | 1 Participants | 1 Participants |
| Maximum tumor size 6 cm tumor | 0 Participants | 1 Participants | 1 Participants |
| Maximum tumor size 9 cm tumor | 0 Participants | 1 Participants | 1 Participants |
| Participants with High Calcium++ No | 5 Participants | 5 Participants | 10 Participants |
| Participants with High Calcium++ Yes | 5 Participants | 2 Participants | 7 Participants |
| Participants with High Lactate Hydrogenase (LDH) No | 0 Participants | 0 Participants | 0 Participants |
| Participants with High Lactate Hydrogenase (LDH) Yes | 10 Participants | 7 Participants | 17 Participants |
| Prior Treatment C, ESHAP, PTX, Gem | 1 Participants | 0 Participants | 1 Participants |
| Prior Treatment CHOP | 2 Participants | 3 Participants | 5 Participants |
| Prior Treatment CHOP, C | 2 Participants | 0 Participants | 2 Participants |
| Prior Treatment CHOP, Hydroxyurea | 1 Participants | 0 Participants | 1 Participants |
| Prior Treatment EPOCH-C | 0 Participants | 1 Participants | 1 Participants |
| Prior Treatment EPOCH-RS | 1 Participants | 1 Participants | 2 Participants |
| Prior Treatment Hydroxyurea | 1 Participants | 1 Participants | 2 Participants |
| Prior Treatment LSG-15, radiation | 0 Participants | 1 Participants | 1 Participants |
| Prior Treatment Medi507, Ontak, HAT | 1 Participants | 0 Participants | 1 Participants |
| Prior Treatment None | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized African American | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized American, from Ghana, Black | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized American from Jamaica, Black | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Barbados, Black | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Ethiopian, Black | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Jamaican | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Jamaican, Black | 5 Participants | 2 Participants | 7 Participants |
| Race/Ethnicity, Customized Peruvian, Hispanic | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Tabago, Black | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment United States | 10 Participants | 8 Participants | 18 Participants |
| Sex: Female, Male Female | 7 Participants | 5 Participants | 12 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants |
| Type of Leukemia Acute | 10 Participants | 3 Participants | 13 Participants |
| Type of Leukemia Lymphoma | 0 Participants | 4 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 8 / 10 | 6 / 8 |
| other Total, other adverse events | 10 / 10 | 8 / 8 |
| serious Total, serious adverse events | 7 / 10 | 6 / 8 |
Outcome results
Primary
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
Population: All 10 patients receiving LMB-2 and at least 25+250 mg/m\^2 Fludarabine/Cyclophosphamide (FC) were evaluable for response.~Of the 8 other patients, only 5 received LMB-2 and were therefore evaluable for response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | Percentage of Participants With a Minimally Durable Clinical Response Rate | Partial Response | 20 percentage of participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | Percentage of Participants With a Minimally Durable Clinical Response Rate | Stable Disease | 20 percentage of participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | Percentage of Participants With a Minimally Durable Clinical Response Rate | Complete Response | 60 percentage of participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | Percentage of Participants With a Minimally Durable Clinical Response Rate | Progressive Disease | 0 percentage of participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | Percentage of Participants With a Minimally Durable Clinical Response Rate | Not Evaluable | 0 percentage of participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | Percentage of Participants With a Minimally Durable Clinical Response Rate | Overall Response | 80 percentage of participants |
| All Other Patients | Percentage of Participants With a Minimally Durable Clinical Response Rate | Progressive Disease | 37.5 percentage of participants |
| All Other Patients | Percentage of Participants With a Minimally Durable Clinical Response Rate | Not Evaluable | 37.5 percentage of participants |
| All Other Patients | Percentage of Participants With a Minimally Durable Clinical Response Rate | Overall Response | 0 percentage of participants |
| All Other Patients | Percentage of Participants With a Minimally Durable Clinical Response Rate | Complete Response | 0 percentage of participants |
| All Other Patients | Percentage of Participants With a Minimally Durable Clinical Response Rate | Stable Disease | 25 percentage of participants |
| All Other Patients | Percentage of Participants With a Minimally Durable Clinical Response Rate | Partial Response | 0 percentage of participants |
Secondary
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
Population: Three participants were non-evaluable. One participant withdrew due to inability to receive second cycle, which was the first cycle containing LMB-2. One participant had progressive disease before first cycle of LMB2, and one participant had progressive disease after first cycle of LMB2
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | Area Under the Plasma Concentration (AUC) - LMB2 | 161 µg/-min/mL |
| All Other Patients | Area Under the Plasma Concentration (AUC) - LMB2 | 144 µg/-min/mL |
Secondary
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
Population: \*Grade 5 (death) event. Data for this outcome measure is reported as in the publication noted in the References module.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Thrombocytopenia | 0 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Leukopenia/lymphopenia | 1 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Anemia | 0 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Transaminases | 1 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Neutropenia | 1 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Fever/chills | 0 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Pneumonitis | 0 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Low cluster of differentiation 4 (CD4) count | 1 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Hypotension/tachycardia | 0 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Rectal hemorrhage | 0 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Bilirubin | 0 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Dysuria | 0 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Bladder infection | 0 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Hypoxia | 0 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Proteinuria | 0 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Sepsis* | 0 Participants |
| All Other Patients | 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 | Fever/chills | 3 Participants |
| All Other Patients | 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 | Pneumonitis | 3 Participants |
| All Other Patients | 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 | Sepsis* | 1 Participants |
| All Other Patients | 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 | Low cluster of differentiation 4 (CD4) count | 1 Participants |
| All Other Patients | 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 | Hypoxia | 1 Participants |
| All Other Patients | 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 | Hypotension/tachycardia | 2 Participants |
| All Other Patients | 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 | Rectal hemorrhage | 1 Participants |
| All Other Patients | 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 | Bilirubin | 1 Participants |
| All Other Patients | 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 | Neutropenia | 9 Participants |
| All Other Patients | 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 | Leukopenia/lymphopenia | 9 Participants |
| All Other Patients | 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 | Dysuria | 1 Participants |
| All Other Patients | 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 | Anemia | 8 Participants |
| All Other Patients | 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 | Transaminases | 4 Participants |
| All Other Patients | 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 | Proteinuria | 1 Participants |
| All Other Patients | 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 | Thrombocytopenia | 5 Participants |
| All Other Patients | 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 | Bladder infection | 1 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Bilirubin | 0 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Fever/chills | 1 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Bladder infection | 0 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Anemia | 0 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Pneumonitis | 0 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Neutropenia | 2 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Proteinuria | 0 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Low cluster of differentiation 4 (CD4) count | 1 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Dysuria | 0 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Leukopenia/lymphopenia | 2 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Hypotension/tachycardia | 0 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Hypoxia | 0 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Thrombocytopenia | 1 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Rectal hemorrhage | 0 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Sepsis* | 0 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Transaminases | 0 Participants |
Secondary
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
Population: Data for this outcome measure is reported as in the publication noted in the References module.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Anemia | 0 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Prothrombin time | 1 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Edema | 0 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Thrombocytopenia | 1 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Pruritis | 1 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Alkaline phosphatase/gamma-glutamyl transferase | 0 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Hypotension/tachycardia | 1 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Neutropenia | 2 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Diarrhea | 1 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Transaminases | 3 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Nausea/vomiting/anorexia | 2 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Fatigue/dizziness | 1 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Leukopenia/lymphopenia | 1 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Fever/chills | 1 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Creatine phosphokinase (CPK) | 0 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Pneumonitis | 0 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Hypomagnesemia | 0 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Proteinuria | 0 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Low cluster of differentiation 4 (CD4) count | 1 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Mucositis | 0 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Lipase | 0 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Abdominal pain | 0 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Hematuria | 1 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Bladder infection | 0 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Bilirubin | 1 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Myalgia/headache | 2 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Dyspnea | 0 Participants |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | 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 | Hypoalbuminemia | 2 Participants |
| All Other Patients | 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 | Fever/chills | 10 Participants |
| All Other Patients | 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 | Creatine phosphokinase (CPK) | 4 Participants |
| All Other Patients | 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 | Mucositis | 3 Participants |
| All Other Patients | 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 | Hypomagnesemia | 3 Participants |
| All Other Patients | 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 | Bilirubin | 2 Participants |
| All Other Patients | 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 | Alkaline phosphatase/gamma-glutamyl transferase | 3 Participants |
| All Other Patients | 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 | Pneumonitis | 3 Participants |
| All Other Patients | 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 | Low cluster of differentiation 4 (CD4) count | 1 Participants |
| All Other Patients | 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 | Lipase | 3 Participants |
| All Other Patients | 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 | Bladder infection | 2 Participants |
| All Other Patients | 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 | Dyspnea | 2 Participants |
| All Other Patients | 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 | Prothrombin time | 1 Participants |
| All Other Patients | 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 | Pruritis | 0 Participants |
| All Other Patients | 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 | Neutropenia | 10 Participants |
| All Other Patients | 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 | Nausea/vomiting/anorexia | 10 Participants |
| All Other Patients | 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 | Leukopenia/lymphopenia | 9 Participants |
| All Other Patients | 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 | Transaminases | 8 Participants |
| All Other Patients | 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 | Hypotension/tachycardia | 8 Participants |
| All Other Patients | 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 | Thrombocytopenia | 8 Participants |
| All Other Patients | 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 | Anemia | 9 Participants |
| All Other Patients | 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 | Myalgia/headache | 7 Participants |
| All Other Patients | 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 | Hematuria | 5 Participants |
| All Other Patients | 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 | Proteinuria | 7 Participants |
| All Other Patients | 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 | Fatigue/dizziness | 4 Participants |
| All Other Patients | 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 | Abdominal pain | 5 Participants |
| All Other Patients | 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 | Diarrhea | 3 Participants |
| All Other Patients | 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 | Hypoalbuminemia | 6 Participants |
| All Other Patients | 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 | Edema | 6 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Dyspnea | 0 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Creatine phosphokinase (CPK) | 0 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Anemia | 1 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Bladder infection | 0 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Abdominal pain | 0 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Myalgia/headache | 2 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Hypoalbuminemia | 1 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Lipase | 0 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Mucositis | 1 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Hematuria | 1 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Pneumonitis | 0 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Low cluster of differentiation 4 (CD4) count | 1 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Proteinuria | 0 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Alkaline phosphatase/gamma-glutamyl transferase | 0 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Diarrhea | 0 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Fever/chills | 1 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Nausea/vomiting/anorexia | 2 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Fatigue/dizziness | 2 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Leukopenia/lymphopenia | 2 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Neutropenia | 2 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Bilirubin | 0 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Transaminases | 1 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Pruritis | 1 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Edema | 0 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Hypotension/tachycardia | 2 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Prothrombin time | 0 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Hypomagnesemia | 0 Participants |
| Fludarabine and Cyclophosphamide: 30 + 300mg/m^2 | 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 | Thrombocytopenia | 2 Participants |
Secondary
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | Duration of Response (Complete Response + Partial Response) | 69.6 Weeks |
| All Other Patients | Duration of Response (Complete Response + Partial Response) | 0 Weeks |
Secondary
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
Population: Three participants were non-evaluable. One participant withdrew due to inability to receive second cycle, which was the first cycle containing LMB-2. One participant had progressive disease before first cycle of LMB2, and one participant had progressive disease after first cycle of LMB2
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | Half Life (t1/2) of LMB-2 | 360 min |
| All Other Patients | Half Life (t1/2) of LMB-2 | 251 min |
Secondary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | Number of Participants With Dose Limiting Toxicity (DLT) | 0 Participants |
| All Other Patients | Number of Participants With Dose Limiting Toxicity (DLT) | 0 Participants |
Secondary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | Number of Participants With Serious and Non-serious Adverse Events | 10 Participants |
| All Other Patients | Number of Participants With Serious and Non-serious Adverse Events | 8 Participants |
Secondary
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
Population: One participant withdrew due to inability to receive second cycle, which was the first cycle containing LMB-2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | Overall Survival (OS) | 18.6 Months |
| All Other Patients | Overall Survival (OS) | 3.75 Months |
Secondary
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | Peak Level of LMB-2 in Adult T-Cell Lymphoma | 602 ng/mL |
| All Other Patients | Peak Level of LMB-2 in Adult T-Cell Lymphoma | 484 ng/mL |
Secondary
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
Population: Three participants were non-evaluable. One participant withdrew due to inability to receive second cycle, which was the first cycle containing LMB-2. One participant had progressive disease before first cycle of LMB2, and one participant had progressive disease after first cycle of LMB2
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | Percentage of Patients Who Developed Neutralizing Antibodies After One or More Cycles of LMB-2 | 40 percentage of participants |
| All Other Patients | Percentage of Patients Who Developed Neutralizing Antibodies After One or More Cycles of LMB-2 | 0 percentage of participants |
Secondary
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
Population: Three participants were non-evaluable. One participant withdrew due to inability to receive second cycle, which was the first cycle containing LMB-2. One participant had progressive disease before first cycle of LMB2, and one participant had progressive disease after first cycle of LMB2
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | Plasma Clearance (CL) of LMB-2 | 109 mL/min |
| All Other Patients | Plasma Clearance (CL) of LMB-2 | 101 mL/min |
Secondary
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
Population: One patient did not have flow cytometry measuring it.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | Post Treatment Effects of LMB-2 + Fludarabine and Cyclophosphamide (FC) on Normal B and T Cell Subsets by Flow Cytometry | Normal T-cells | 28 Cells/µL |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | Post Treatment Effects of LMB-2 + Fludarabine and Cyclophosphamide (FC) on Normal B and T Cell Subsets by Flow Cytometry | Normal CD4+ cells | 99.5 Cells/µL |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | Post Treatment Effects of LMB-2 + Fludarabine and Cyclophosphamide (FC) on Normal B and T Cell Subsets by Flow Cytometry | Normal CD8+ cells | 28 Cells/µL |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | Post Treatment Effects of LMB-2 + Fludarabine and Cyclophosphamide (FC) on Normal B and T Cell Subsets by Flow Cytometry | Normal B-cells | 8 Cells/µL |
| All Other Patients | Post Treatment Effects of LMB-2 + Fludarabine and Cyclophosphamide (FC) on Normal B and T Cell Subsets by Flow Cytometry | Normal B-cells | 0.5 Cells/µL |
| All Other Patients | Post Treatment Effects of LMB-2 + Fludarabine and Cyclophosphamide (FC) on Normal B and T Cell Subsets by Flow Cytometry | Normal T-cells | 23.5 Cells/µL |
| All Other Patients | Post Treatment Effects of LMB-2 + Fludarabine and Cyclophosphamide (FC) on Normal B and T Cell Subsets by Flow Cytometry | Normal CD8+ cells | 23.5 Cells/µL |
| All Other Patients | Post Treatment Effects of LMB-2 + Fludarabine and Cyclophosphamide (FC) on Normal B and T Cell Subsets by Flow Cytometry | Normal CD4+ cells | 186 Cells/µL |
Secondary
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | Progression Free Survival (PFS) | 11.6 Months |
| All Other Patients | Progression Free Survival (PFS) | 1.05 Months |
Comparison: Published response duration of 15 patients with leukemic adult T cell leukemia treated with Alemtuzumab.p-value: <0.0001Kaplan Meier
Secondary
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
Population: The number 8 represents the number of responders in the Arm/Group and the number 2 represents the number of non-responders in the Arm/Group.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | Soluble Cluster of Differentiation 25 (sCD25) Between Responders and Nonresponders | Median sCD25 PRE-treatment for responders | 31893 pg/ml |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | Soluble Cluster of Differentiation 25 (sCD25) Between Responders and Nonresponders | Median sCD25 PRE-treatment for non-responders | 66419 pg/ml |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | Soluble Cluster of Differentiation 25 (sCD25) Between Responders and Nonresponders | Soluble CD25, lowest post-treatment (nadir) value | 1094 pg/ml |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | Soluble Cluster of Differentiation 25 (sCD25) Between Responders and Nonresponders | Median sCD25 Nadir for non-responders | 70713 pg/ml |
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | Soluble Cluster of Differentiation 25 (sCD25) Between Responders and Nonresponders | Median sCD25 Nadir for responders | 1082 pg/ml |
| All Other Patients | Soluble Cluster of Differentiation 25 (sCD25) Between Responders and Nonresponders | Median sCD25 PRE-treatment for non-responders | 17079 pg/ml |
| All Other Patients | Soluble Cluster of Differentiation 25 (sCD25) Between Responders and Nonresponders | Soluble CD25, lowest post-treatment (nadir) value | 34591 pg/ml |
| All Other Patients | Soluble Cluster of Differentiation 25 (sCD25) Between Responders and Nonresponders | Median sCD25 Nadir for non-responders | 34591 pg/ml |
Secondary
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
Population: Three participants were non-evaluable. One participant withdrew due to inability to receive second cycle, which was the first cycle containing LMB-2. One participant had progressive disease before first cycle of LMB2, and one participant had progressive disease after first cycle of LMB2
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Leukemic Patients Receiving LMB-2 & At Least 25+250 mg/m^2 FC | Volume of Distribution of LMB-2 | 49.6 Liters |
| All Other Patients | Volume of Distribution of LMB-2 | 26.6 Liters |