Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Lymphosarcoma

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

* 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

BL-8040

Nelarabine

Geoffrey L Uy, M.D.

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.

BL-8040 and Nelarabine for Relapsed or Refractory T-Acute Lymphoblastic Leukemia/ Lymphoblastic Lymphoma

A Phase IIa Study of BL-8040 in Combination With Nelarabine for Relapsed or Refractory T-Acute Lymphoblastic Leukemia/ Lymphoblastic Lymphoma

Interaction of pretreatment disease and white blood cell count on clinical outcome

Interaction of pretreatment disease and performance status on clinical outcome

Interaction of pretreatment disease and immunophenotype on clinical outcome

Interaction of pretreatment disease and cytogenetics on clinical outcome

Interaction of pretreatment disease and CXCR4 expression on lymphoblasts on clinical outcome

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

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 mobilization of lymphoblasts into the peripheral circulation

Pharmacodynamic effects of BL-8040 on T-lymphoblasts as measured by inhibition of CXCR4 signaling on lymphoblasts

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.

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

* 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

* 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

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.

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.

Defined as the date of first dose of study drug to the date of death from any cause.

Estimate rate of patients who proceed to alloHCT after treatment

The Leukemia and Lymphoma Society

National Institutes of Health (NIH)

National Cancer Institute (NCI)

Washington University School of Medicine

Arm 1: BL-8040 and Nelarabine

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Geoffrey L. Uy, M.D.

Grade 3-5 white blood cell increased post BL-8040 injection

Grade 1-2 lymphadenopathy worsening

Grade 3-5 leukocytosis

Grade 1-2 infarct

Grade 1-2 chest pain - cardiac

Grade 1-2 pericardial effusion

Grade 1-2 sinus bradycardia

Grade 1-2 sinus tachycardia

Grade 1-2 tinnitus

Grade 3-5 abdominal pain at study drug injection site

Grade 1-2 constipation

Grade 1-2 diarrhea

Grade 3-5 diarrhea

Grade 1-2 gastrointestinal hemorrhage

Grade 1-2 mucositis oral

Grade 1-2 nausea

Grade 1-2 oral hemorrhage

Grade 1-2 vomiting

Grade 1-2 "feeling funny" post transfusion

Grade 1-2 biopsy pain

Grade 1-2 catheter pain from replacement

Grade 3-5 disease progression

Grade 1-2 pain at CVC site

Grade 1-2 pain at right jugular Hohn catheter

Grade 1-2 injection site reaction (rash)

Grade 1-2 redness at Hohn catheter insertion site

Grade 1-2 right knee pain

Grade 1-2 diffuse pain

Grade 1-2 pain in leg

Grade 1-2 pain, skin nodule at biopsy site

Grade 1-2 transfusion reaction to packed red blood cells

Grade 1-2 chills

Grade 1-2 edema limbs

Grade 3-5 fatigue

Grade 1-2 fever

Grade 1-2 gait disturbance

Grade 1-2 injection site reaction

Grade 1-2 localized edema

Grade 1-2 malaise

Grade 1-2 non-cardiac chest pain

Grade 3-5 non-cardiac chest pain

Grade 1-2 allergic reaction

Grade 3-5 lung infection

Grade 3-5 sepsis

Grade 1-2 sinusitis

Grade 1-2 upper respiratory infection

Grade 1-2 urinary tract infection

Grade 3-5 urinary tract infection

Grade 1-2 bruising

Grade 1-2 fall

Grade 1-2 hip fracture

Grade 1-2 activated partial thromboplastin time prolonged

Grade 3-5 activated partial thromboplastin time prolonged

Grade 1-2 alanine aminotransferase increased

Grade 3-5 alanine aminotransferase increased

Grade 1-2 alkaline phosphatase

Grade 1-2 aspartate aminotransferase increased

Grade 3-5 aspartate aminotransferase increased

Grade 1-2 cardiac troponin T increased

Grade 1-2 creatinine increased

Grade 1-2 electrocardiogram QT corrected interval prolonged

Grade 3-5 electrocardiogram QT corrected interval prolonged

Grade 1-2 INR increased

Grade 1-2 serum amylase increased

Grade 1-2 weight gain

Grade 1-2 weight loss

Grade 1-2 anorexia

Grade 3-5 anorexia

Grade 1-2 dehydration

Grade 3-5 hyperglycemia

Grade 1-2 hyperuricemia

Grade 3-5 hyperuricemia

Grade 1-2 hypoalbuminemia

Grade 3-5 hypokalemia

Grades 3-5 hypomagmesemia

Grade 3-5 hypophosphatemia

Grade 3-5 tumor lysis syndrome

Grade 3-5 muscle weakness lower limb

Grade 1-2 neck pain

Grade 1-2 osteoporosis

Grade 1-2 pain in extremity

Grade 1-2 altered mental status

Grade 3-5 altered mental status

Grade 1-2 dizziness

Grade 1-2 headache

Grade 1-2 paresthesia

Grade 3-5 peripheral motor neuropathy

Grade 1-2 peripheral sensory neuropathy

Grade 1-2 somnolence

Grade 3-5 syncope

Grade 1-2 tremor

Grade 1-2 anxiety

Grade 1-2 confusion

Grade 1-2 depression

Grade 1-2 insomnia

Grade 1-2 hematuria

Grade 1-2 proteinuria

Grade 1-2 urinary incontinence

Grade 1-2 urinary retention

Grade 1-2 urinary tract pain

Safety and Tolerability of Regimen as Measured by Number of Participants With Adverse Events

2 participants were not evaluable for this outcome measure because they stopped treatment prior to disease response assessment.

Composite Complete Remission Rate (CRc=CR+CRi)

Overall Response Rate (CR, CRi + PR)

Time to Response

Duration of Response

Event-free Survival (EFS)

Overall Survival

Rate of Patients Who Proceed to alloHCT After Treatment

Interaction of Pretreatment Disease and White Blood Cell Count on Clinical Outcome

Interaction of Pretreatment Disease and Performance Status on Clinical Outcome

Interaction of Pretreatment Disease and Immunophenotype on Clinical Outcome

Interaction of Pretreatment Disease and Cytogenetics on Clinical Outcome

Interaction of Pretreatment Disease and CXCR4 Expression on Lymphoblasts on Clinical Outcome

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

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 Mobilization of Lymphoblasts Into the Peripheral Circulation

Pharmacodynamic Effects of BL-8040 on T-lymphoblasts as Measured by Inhibition of CXCR4 Signaling on Lymphoblasts

Overall Study

Spots Global Cancer Trial Database for adult t lymphoblastic lymphoma