T-Acute Lymphoblastic Leukemia, Adult T Lymphoblastic Lymphoma
Conditions
Brief summary
The outcome of patients with relapsed or refractory adult T-acute lymphoblastic leukemia (T-ALL) and the related disease T-lymphoblastic lymphoma (T-LBL) is extremely poor with 30% of the patients responding to first salvage therapy and long-term survival of only 10%. Therefore, novel therapies for patients with relapsed/refractory T-ALL/LBL represent an unmet clinical need. Recent data provide strong evidence that CXCR4 signaling plays a major role in T-cell leukemia cell maintenance and leukemia initiating activity, and targeting CXCR4 signaling in T-ALL cells reduces tumor growth in an animal model. In this study, the investigators propose that the addition of BL-8040 to nelarabine as a salvage therapy for patients with relapsed/refractory T-ALL/LBL will result in a higher complete remission (CR) rate than nelarabine alone without an increase in toxicity and will allow patients to proceed to a potentially curative allogeneic hematopoietic cell transplant.
Interventions
DRUGBL-8040
DRUGNelarabine
Sponsors
The Leukemia and Lymphoma Society
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Washington University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of T-acute lymphoblastic leukemia/ lymphoblastic lymphoma according to WHO criteria which has relapsed or is refractory to chemotherapy. * Peripheral blood lymphoblasts ≤ 50,000 mcL. Hydroxyurea and/or leukapheresis is permitted to reduce the peripheral blast count prior to enrollment and treatment. * Age ≥ 18 years * ECOG performance status ≤ 2. * Adequate organ function defined as: * Calculated creatinine clearance ≥ 50 ml/min using the Cockroft-Gault formula * AST, ALT, total bilirubin ≤ 2 x institutional ULN except for Gilbert's disease or when in the opinion of treating physician elevated levels are due to direct involvement of leukemia (e.g., hepatic infiltration or biliary obstruction due to leukemia), in which case ALT and AST may be elevated up to ≤ 5 x IULN. * Women of childbearing potential and men must agree to use adequate contraception with a highly effective method (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Abstinence is acceptable if this is the established and preferred contraception for the subject. * Female subjects must have a negative urine or serum pregnancy test within 72 hours prior to start of study treatment if of childbearing potential or be of non-childbearing potential. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The serum pregnancy test must be negative for the subject to be eligible. Non-childbearing potential is defined as: \*≥ 45 years of age and has not had menses for \> 2 years * Amenorrheic for \> 2 years without a hysterectomy and oophorectomy and a FSH value in the postmenopausal range upon pretrial (screening) evaluation * Post-hysterectomy, oophorectomy, or tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure. * Able to understand and willing to sign an IRB-approved written informed consent document.
Exclusion criteria
* Previous treatment with nelarabine for relapsed or refractory disease. * Pregnant or nursing. * Received any other investigational agent or systemic cytotoxic chemotherapy within the preceding 2 weeks. * Active CNS involvement with leukemia * Active HIV or hepatitis B or C infection. * Any medical condition which, in the opinion of the clinical investigator, would interfere with the evaluation of the patient. Subjects with a clinically significant or unstable medical or surgical condition or any other condition that cannot be well-controlled by the allowed medications permitted in the study protocol that would preclude safe and complete study participation, as determined by medical history, physical examinations, laboratory tests, and according to the investigator's judgment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Up to 30 days after completion of treatment (median follow-up of 51.5 days, full range 24-120 days) | The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all adverse event reporting. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (CR, CRi + PR) | Through completion of treatment (median treatment length of 37.5 days, full range of 13-90 days) | * Complete remission (CR) = an absolute neutrophil count (segs and bands) \> 1,000/mcL, no circulating lymphoblasts, platelets ≥ 100,000/mcL; and \< 5% marrow leukemia blast cells with complete disappearance of all measurable disease as confirmed by physical examination, CT scan and/or FDG-PET (Deauville criteria score of 1, 2, or 3) * Morphologic complete remission with incomplete blood count recovery (CRi)=Defined as CR with the exception of neutropenia \< 1,000/mcL or thrombocytopenia \<100,000/mcL * Partial remission (PR)=A PR requires all of the CR criteria except that marrow may still contain 5-25% leukemia blast cells. An absolute neutrophil count (segs and bands) ≥ 1000/mcL, no circulating blasts, and platelets \> 100,000/mcL are requires as for a CR. For patients with measurable disease, a reduction of 50% or more in the sum of the products of the perpendicular diameters of all measurable lesions compared with pretreatment measurements and with no new or enlarging lesions |
| Time to Response | Through completion of treatment (median treatment length of 37.5 days, full range of 13-90 days) | * Response is CR or CRi * Complete remission (CR) = an absolute neutrophil count (segs and bands) \> 1,000/mcL, no circulating lymphoblasts, platelets ≥ 100,000/mcL; and \< 5% marrow leukemia blast cells with complete disappearance of all measurable disease as confirmed by physical examination, CT scan and/or FDG-PET (Deauville criteria score of 1, 2, or 3) * Morphologic complete remission with incomplete blood count recovery (CRi)=Defined as CR with the exception of neutropenia \< 1,000/mcL or thrombocytopenia \<100,000/mcL |
| Duration of Response | Through date of recurrence or completion of follow-up (maximum of 2 years after completion of treatment) | Defined as the interval from the date CR/CRi is documented to the date of recurrence or completion of follow-up if recurrence has not occurred. |
| Composite Complete Remission Rate (CRc=CR+CRi) | Completion of treatment (approximately 12 weeks) | Complete remission (CR) = an absolute neutrophil count (segs and bands) \> 1,000/mcL, no circulating lymphoblasts, platelets ≥ 100,000/mcL; and \< 5% marrow leukemia blast cells with complete disappearance of all measurable disease as confirmed by physical examination, CT scan and/or FDG-PET (Deauville criteria score of 1, 2, or 3) -Morphologic complete remission with incomplete blood count recovery (CRi)=Defined as CR with the exception of neutropenia \< 1,000/mcL or thrombocytopenia \<100,000/mcL |
| Overall Survival | Through completion of follow-up (maximum of 2 years after completion of treatment) | Defined as the date of first dose of study drug to the date of death from any cause. |
| Rate of Patients Who Proceed to alloHCT After Treatment | Through completion of treatment (median treatment length of 37.5 days, full range of 13-90 days) | Estimate rate of patients who proceed to alloHCT after treatment |
| Event-free Survival (EFS) | Through completion of follow-up (maximum of 2 years after completion of treatment) | EFS is defined as the interval from the date of first dose of study drug to date of treatment failure, recurrence, of death due to any cause. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamic Effects of BL-8040 on T-lymphoblasts as Measured by Mobilization of Lymphoblasts Into the Peripheral Circulation | Completion of treatment (approximately 12 weeks) | Pharmacodynamic effects of BL-8040 on T-lymphoblasts as measured by mobilization of lymphoblasts into the peripheral circulation |
| Interaction of Pretreatment Disease and White Blood Cell Count on Clinical Outcome | Up to 2 years after completion of treatment (approximately 116 weeks) | Interaction of pretreatment disease and white blood cell count on clinical outcome |
| Pharmacodynamic Effects of BL-8040 on T-lymphoblasts as Measured by Inhibition of CXCR4 Signaling on Lymphoblasts | Completion of treatment (approximately 12 weeks) | Pharmacodynamic effects of BL-8040 on T-lymphoblasts as measured by inhibition of CXCR4 signaling on lymphoblasts |
| Interaction of Pretreatment Disease and Performance Status on Clinical Outcome | Up to 2 years after completion of treatment (approximately 116 weeks) | Interaction of pretreatment disease and performance status on clinical outcome |
| Interaction of Pretreatment Disease and Immunophenotype on Clinical Outcome | Up to 2 years after completion of treatment (approximately 116 weeks) | Interaction of pretreatment disease and immunophenotype on clinical outcome |
| Interaction of Pretreatment Disease and Cytogenetics on Clinical Outcome | Up to 2 years after completion of treatment (approximately 116 weeks) | Interaction of pretreatment disease and cytogenetics on clinical outcome |
| Interaction of Pretreatment Disease and CXCR4 Expression on Lymphoblasts on Clinical Outcome | Up to 2 years after completion of treatment (approximately 116 weeks) | Interaction of pretreatment disease and CXCR4 expression on lymphoblasts on clinical outcome |
| Interaction of Pretreatment Disease and Morphology on Clinical Outcome | Up to 2 years after completion of treatment (approximately 116 weeks) | Interaction of pretreatment disease and morphology on clinical outcome |
| Pharmacodynamic Effects of BL-8040 on T-lymphoblasts as Measured by Alterations in Lymphoblast Cell Cycle Status | Completion of treatment (approximately 12 weeks) | Pharmacodynamic effects of BL-8040 on T-lymphoblasts as measured by alterations in lymphoblast cell cycle status |
| Pharmacodynamic Effects of BL-8040 on T-lymphoblasts as Measured by Induction of Apoptosis in Lymphoblasts | Completion of treatment (approximately 12 weeks) | Pharmacodynamic effects of BL-8040 on T-lymphoblasts as measured by induction of apoptosis in lymphoblasts |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: BL-8040 and Nelarabine * Cycle 1: BL-8040 subcutaneous daily from Day 1 to Day 6 and nelarabine intravenously over 2 hours on Days 2, 4, and 6
* Cycles 2-4: BL-8040 subcutaneous daily from Day 1 to Day 5 and nelarabine intravenously over 2 hours on Days 1, 3, and 5
* Treatment may be repeated every 21 days for up to 4 cycles | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
| Overall Study | Rapid decline - went on hospice | 1 |
Baseline characteristics
| Characteristic | Arm 1: BL-8040 and Nelarabine |
|---|---|
| Age, Continuous | 30 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 9 / 12 |
| other Total, other adverse events | 12 / 12 |
| serious Total, serious adverse events | 8 / 12 |
Outcome results
Primary
Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events
The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all adverse event reporting.
Time frame: Up to 30 days after completion of treatment (median follow-up of 51.5 days, full range 24-120 days)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 hypoxia | 2 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 white blood cell increased post BL-8040 injection | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 lymphadenopathy worsening | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 leukocytosis | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 infarct | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 chest pain - cardiac | 2 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 pericardial effusion | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 sinus bradycardia | 2 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 sinus tachycardia | 3 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 tinnitus | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 abdominal pain at study drug injection site | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 constipation | 2 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 diarrhea | 2 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 diarrhea | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 gastrointestinal hemorrhage | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 mucositis oral | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 nausea | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 oral hemorrhage | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 vomiting | 4 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 feeling funny post transfusion | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 biopsy pain | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 catheter pain from replacement | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 disease progression | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 pain at CVC site | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 pain at right jugular Hohn catheter | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 injection site reaction (rash) | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 redness at Hohn catheter insertion site | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 right knee pain | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 diffuse pain | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 pain in leg | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 pain, skin nodule at biopsy site | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 transfusion reaction to packed red blood cells | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 chills | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 edema limbs | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 fatigue | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 fever | 3 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 gait disturbance | 2 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 injection site reaction | 8 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 localized edema | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 malaise | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 non-cardiac chest pain | 2 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 non-cardiac chest pain | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 allergic reaction | 3 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 lung infection | 3 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 sepsis | 2 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 sinusitis | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 upper respiratory infection | 2 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 urinary tract infection | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 urinary tract infection | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 bruising | 2 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 fall | 3 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 hip fracture | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 activated partial thromboplastin time prolonged | 2 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 activated partial thromboplastin time prolonged | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 alanine aminotransferase increased | 3 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 alanine aminotransferase increased | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 alkaline phosphatase | 5 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 aspartate aminotransferase increased | 3 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 aspartate aminotransferase increased | 2 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 cardiac troponin T increased | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 creatinine increased | 4 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 electrocardiogram QT corrected interval prolonged | 2 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 electrocardiogram QT corrected interval prolonged | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 INR increased | 2 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 serum amylase increased | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 weight gain | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 weight loss | 3 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 anorexia | 6 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 anorexia | 2 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 dehydration | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 hyperglycemia | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 hyperuricemia | 2 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 hyperuricemia | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 hypoalbuminemia | 5 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 hypokalemia | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grades 3-5 hypomagmesemia | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 hypophosphatemia | 4 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 tumor lysis syndrome | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 muscle weakness lower limb | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 neck pain | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 osteoporosis | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 pain in extremity | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 altered mental status | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 altered mental status | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 dizziness | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 headache | 3 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 paresthesia | 2 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 peripheral motor neuropathy | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 peripheral sensory neuropathy | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 somnolence | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 syncope | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 tremor | 2 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 anxiety | 2 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 confusion | 2 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 depression | 2 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 insomnia | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 hematuria | 3 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 proteinuria | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 urinary incontinence | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 urinary retention | 2 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 urinary tract pain | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 irregular menstruation | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 hemoptysis | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 atelectasis | 3 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 dyspnea | 2 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 dyspnea | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 hypoxia | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 nasal congestion | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 pleural effusion | 3 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 productive cough | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 pulmonary edema | 2 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 cellulitis | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 dry skin | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 erythema multiforme | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 pruritus | 2 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 purpura | 3 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 rash maculo-papular | 2 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 scalp pain | 1 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 hypertension | 4 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 hypertension | 3 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 1-2 hypotension | 2 Participants |
| Arm 1: BL-8040 and Nelarabine | Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events | Grade 3-5 hypotension | 1 Participants |
Secondary
Composite Complete Remission Rate (CRc=CR+CRi)
Complete remission (CR) = an absolute neutrophil count (segs and bands) \> 1,000/mcL, no circulating lymphoblasts, platelets ≥ 100,000/mcL; and \< 5% marrow leukemia blast cells with complete disappearance of all measurable disease as confirmed by physical examination, CT scan and/or FDG-PET (Deauville criteria score of 1, 2, or 3) -Morphologic complete remission with incomplete blood count recovery (CRi)=Defined as CR with the exception of neutropenia \< 1,000/mcL or thrombocytopenia \<100,000/mcL
Time frame: Completion of treatment (approximately 12 weeks)
Population: 2 participants were not evaluable for this outcome measure because they stopped treatment prior to disease response assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: BL-8040 and Nelarabine | Composite Complete Remission Rate (CRc=CR+CRi) | 4 Participants |
Secondary
Duration of Response
Defined as the interval from the date CR/CRi is documented to the date of recurrence or completion of follow-up if recurrence has not occurred.
Time frame: Through date of recurrence or completion of follow-up (maximum of 2 years after completion of treatment)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: BL-8040 and Nelarabine | Duration of Response | 280 days |
Secondary
Event-free Survival (EFS)
EFS is defined as the interval from the date of first dose of study drug to date of treatment failure, recurrence, of death due to any cause.
Time frame: Through completion of follow-up (maximum of 2 years after completion of treatment)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: BL-8040 and Nelarabine | Event-free Survival (EFS) | 23 days |
Secondary
Overall Response Rate (CR, CRi + PR)
* Complete remission (CR) = an absolute neutrophil count (segs and bands) \> 1,000/mcL, no circulating lymphoblasts, platelets ≥ 100,000/mcL; and \< 5% marrow leukemia blast cells with complete disappearance of all measurable disease as confirmed by physical examination, CT scan and/or FDG-PET (Deauville criteria score of 1, 2, or 3) * Morphologic complete remission with incomplete blood count recovery (CRi)=Defined as CR with the exception of neutropenia \< 1,000/mcL or thrombocytopenia \<100,000/mcL * Partial remission (PR)=A PR requires all of the CR criteria except that marrow may still contain 5-25% leukemia blast cells. An absolute neutrophil count (segs and bands) ≥ 1000/mcL, no circulating blasts, and platelets \> 100,000/mcL are requires as for a CR. For patients with measurable disease, a reduction of 50% or more in the sum of the products of the perpendicular diameters of all measurable lesions compared with pretreatment measurements and with no new or enlarging lesions
Time frame: Through completion of treatment (median treatment length of 37.5 days, full range of 13-90 days)
Population: 2 participants were not evaluable for this outcome measure because they stopped treatment prior to disease response assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: BL-8040 and Nelarabine | Overall Response Rate (CR, CRi + PR) | 5 Participants |
Secondary
Overall Survival
Defined as the date of first dose of study drug to the date of death from any cause.
Time frame: Through completion of follow-up (maximum of 2 years after completion of treatment)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: BL-8040 and Nelarabine | Overall Survival | 95 days |
Secondary
Rate of Patients Who Proceed to alloHCT After Treatment
Estimate rate of patients who proceed to alloHCT after treatment
Time frame: Through completion of treatment (median treatment length of 37.5 days, full range of 13-90 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: BL-8040 and Nelarabine | Rate of Patients Who Proceed to alloHCT After Treatment | 3 Participants |
Secondary
Time to Response
* Response is CR or CRi * Complete remission (CR) = an absolute neutrophil count (segs and bands) \> 1,000/mcL, no circulating lymphoblasts, platelets ≥ 100,000/mcL; and \< 5% marrow leukemia blast cells with complete disappearance of all measurable disease as confirmed by physical examination, CT scan and/or FDG-PET (Deauville criteria score of 1, 2, or 3) * Morphologic complete remission with incomplete blood count recovery (CRi)=Defined as CR with the exception of neutropenia \< 1,000/mcL or thrombocytopenia \<100,000/mcL
Time frame: Through completion of treatment (median treatment length of 37.5 days, full range of 13-90 days)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: BL-8040 and Nelarabine | Time to Response | 20 days |
Other Pre-specified
Interaction of Pretreatment Disease and CXCR4 Expression on Lymphoblasts on Clinical Outcome
Interaction of pretreatment disease and CXCR4 expression on lymphoblasts on clinical outcome
Time frame: Up to 2 years after completion of treatment (approximately 116 weeks)
Other Pre-specified
Interaction of Pretreatment Disease and Cytogenetics on Clinical Outcome
Interaction of pretreatment disease and cytogenetics on clinical outcome
Time frame: Up to 2 years after completion of treatment (approximately 116 weeks)
Other Pre-specified
Interaction of Pretreatment Disease and Immunophenotype on Clinical Outcome
Interaction of pretreatment disease and immunophenotype on clinical outcome
Time frame: Up to 2 years after completion of treatment (approximately 116 weeks)
Other Pre-specified
Interaction of Pretreatment Disease and Morphology on Clinical Outcome
Interaction of pretreatment disease and morphology on clinical outcome
Time frame: Up to 2 years after completion of treatment (approximately 116 weeks)
Other Pre-specified
Interaction of Pretreatment Disease and Performance Status on Clinical Outcome
Interaction of pretreatment disease and performance status on clinical outcome
Time frame: Up to 2 years after completion of treatment (approximately 116 weeks)
Other Pre-specified
Interaction of Pretreatment Disease and White Blood Cell Count on Clinical Outcome
Interaction of pretreatment disease and white blood cell count on clinical outcome
Time frame: Up to 2 years after completion of treatment (approximately 116 weeks)
Other Pre-specified
Pharmacodynamic Effects of BL-8040 on T-lymphoblasts as Measured by Alterations in Lymphoblast Cell Cycle Status
Pharmacodynamic effects of BL-8040 on T-lymphoblasts as measured by alterations in lymphoblast cell cycle status
Time frame: Completion of treatment (approximately 12 weeks)
Other Pre-specified
Pharmacodynamic Effects of BL-8040 on T-lymphoblasts as Measured by Induction of Apoptosis in Lymphoblasts
Pharmacodynamic effects of BL-8040 on T-lymphoblasts as measured by induction of apoptosis in lymphoblasts
Time frame: Completion of treatment (approximately 12 weeks)
Other Pre-specified
Pharmacodynamic Effects of BL-8040 on T-lymphoblasts as Measured by Inhibition of CXCR4 Signaling on Lymphoblasts
Pharmacodynamic effects of BL-8040 on T-lymphoblasts as measured by inhibition of CXCR4 signaling on lymphoblasts
Time frame: Completion of treatment (approximately 12 weeks)
Other Pre-specified
Pharmacodynamic Effects of BL-8040 on T-lymphoblasts as Measured by Mobilization of Lymphoblasts Into the Peripheral Circulation
Pharmacodynamic effects of BL-8040 on T-lymphoblasts as measured by mobilization of lymphoblasts into the peripheral circulation
Time frame: Completion of treatment (approximately 12 weeks)