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NCT02763384

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

Terminated Phase 2 Results posted Last updated 31 October 2023
What this trial tests

Phase 2 trial testing BL-8040 in T-Acute Lymphoblastic Leukemia in 12 participants. Terminated before completion.

Timeline
2 December 2016
Primary endpoint
11 February 2022
22 May 2022

Quick facts

Lead sponsorWashington University School of Medicine
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment12
Start date2 December 2016
Primary completion11 February 2022
Estimated completion22 May 2022
Sites2 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Washington University School of Medicine

Who can join

18 and older, any sex, with T-Acute Lymphoblastic Leukemia or Adult T Lymphoblastic Lymphoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

Grade 3-5 white blood cell increased post BL-8040 injection
GroupValue95% CI
Arm 1: BL-8040 and Nelarabine1
Grade 1-2 lymphadenopathy worsening
GroupValue95% CI
Arm 1: BL-8040 and Nelarabine1
Grade 3-5 leukocytosis
GroupValue95% CI
Arm 1: BL-8040 and Nelarabine1
Grade 1-2 infarct
GroupValue95% CI
Arm 1: BL-8040 and Nelarabine1
Grade 1-2 chest pain - cardiac
GroupValue95% CI
Arm 1: BL-8040 and Nelarabine2
Grade 1-2 pericardial effusion
GroupValue95% CI
Arm 1: BL-8040 and Nelarabine1
Grade 1-2 sinus bradycardia
GroupValue95% CI
Arm 1: BL-8040 and Nelarabine2
Grade 1-2 sinus tachycardia
GroupValue95% CI
Arm 1: BL-8040 and Nelarabine3
Composite Complete Remission Rate (CRc=CR+CRi) Secondary · 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

GroupValue95% CI
Arm 1: BL-8040 and Nelarabine4
Overall Response Rate (CR, CRi + PR) Secondary · 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 co

GroupValue95% CI
Arm 1: BL-8040 and Nelarabine5
Time to Response Secondary · 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

GroupValue95% CI
Arm 1: BL-8040 and Nelarabine2020 – 39
Duration of Response Secondary · 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.

GroupValue95% CI
Arm 1: BL-8040 and Nelarabine28054 – 471
Event-free Survival (EFS) Secondary · 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.

GroupValue95% CI
Arm 1: BL-8040 and Nelarabine2313 – 314
Overall Survival Secondary · 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.

GroupValue95% CI
Arm 1: BL-8040 and Nelarabine9524 – 440
Rate of Patients Who Proceed to alloHCT After Treatment Secondary · 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

GroupValue95% CI
Arm 1: BL-8040 and Nelarabine3

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected from first dose of study treatment through 30 days after the last study treatment (maximum of 4 cycles of treatment - each cycle is 21 days). All-cause mortality was collected from first dose of study treatment through completion of follow-up (maximum of 2 years following completion of treatment).. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm 1: BL-8040 and Nelarabine
Serious: 8/12 (67%)
Deaths: 9/12

Serious adverse events (12 terms)

ReactionSystemArm 1: BL-8040 and Nelarab…
SepsisInfections and infestations
LeukocytosisBlood and lymphatic system disorders
Chest pain - cardiacCardiac disorders
FatigueGeneral disorders
Non-cardiac chest painGeneral disorders
Lung infectionInfections and infestations
Hip fractureInjury, poisoning and procedural complications
Pain at BL-8040 injection siteInjury, poisoning and procedural complications
Disease progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Altered mental statusNervous system disorders
Peripheral motor neuropathyNervous system disorders
HypotensionVascular disorders
Other adverse events (101 terms — click to expand)

ReactionSystemArm 1: BL-8040 and Nelarab…
Injection site reactionGeneral disorders
AnorexiaMetabolism and nutrition disorders
HypertensionVascular disorders
Alkaline phosphatase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
HypoalbuminemiaMetabolism and nutrition disorders
VomitingGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
Creatinine increasedInvestigations
HypophosphatemiaMetabolism and nutrition disorders
Sinus tachycardiaCardiac disorders
DiarrheaGastrointestinal disorders
FeverGeneral disorders
Allergic reactionImmune system disorders
FallInjury, poisoning and procedural complications
Activated partial thromboplastin time prolongedInvestigations
Electrocardiogram QT corrected interval prolongedInvestigations
Weight lossInvestigations
HyperuricemiaMetabolism and nutrition disorders
HeadacheNervous system disorders
HematuriaRenal and urinary disorders
AtelectasisRespiratory, thoracic and mediastinal disorders
DyspneaRespiratory, thoracic and mediastinal disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
PurpuraSkin and subcutaneous tissue disorders
Sinus bradycardiaCardiac disorders
ConstipationGastrointestinal disorders
Gait disturbanceGeneral disorders
Non-cardiac chest painGeneral disorders
Lung infectionInfections and infestations
Upper respiratory infectionInfections and infestations
Urinary tract infectionInfections and infestations
BruisingInjury, poisoning and procedural complications
INR increasedInvestigations
ParesthesiaNervous system disorders
TremorNervous system disorders
AnxietyPsychiatric disorders
ConfusionPsychiatric disorders
DepressionPsychiatric disorders

Most-reported serious reactions: Sepsis, Leukocytosis, Chest pain - cardiac, Fatigue, Non-cardiac chest pain, Lung infection, Hip fracture, Pain at BL-8040 injection site.

Data from ClinicalTrials.gov NCT02763384 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeting cytokine and chemokine signaling pathways for cancer therapy.
    Yi M, Li T, Niu M, Zhang H, et al · · 2024 · cited 264× · PMID 39034318 · DOI 10.1038/s41392-024-01868-3
  2. Leukaemia: a model metastatic disease.
    Whiteley AE, Price TT, Cantelli G, Sipkins DA. · · 2021 · cited 139× · PMID 33953370 · DOI 10.1038/s41568-021-00355-z
  3. Targeting CXCR4 in AML and ALL.
    Cancilla D, Rettig MP, DiPersio JF. · · 2020 · cited 84× · PMID 33014834 · DOI 10.3389/fonc.2020.01672
  4. Central nervous system involvement in childhood acute lymphoblastic leukemia: challenges and solutions.
    Thastrup M, Duguid A, Mirian C, Schmiegelow K, et al · · 2022 · cited 71× · PMID 36266325 · DOI 10.1038/s41375-022-01714-x
  5. CXCR4 in Waldenström's Macroglobulinema: chances and challenges.
    Kaiser LM, Hunter ZR, Treon SP, Buske C. · · 2021 · cited 62× · PMID 33273682 · DOI 10.1038/s41375-020-01102-3
  6. Facts and Challenges in Immunotherapy for T-Cell Acute Lymphoblastic Leukemia.
    Bayón-Calderón F, Toribio ML, González-García S. · · 2020 · cited 42× · PMID 33081391 · DOI 10.3390/ijms21207685
  7. Targeting chemokines for acute lymphoblastic leukemia therapy.
    Hong Z, Wei Z, Xie T, Fu L, et al · · 2021 · cited 35× · PMID 33743810 · DOI 10.1186/s13045-021-01060-y
  8. Mesenchymal Stromal Cells (MSCs): An Ally of B-Cell Acute Lymphoblastic Leukemia (B-ALL) Cells in Disease Maintenance and Progression within the Bone Marrow Hematopoietic Niche.
    Fallati A, Di Marzo N, D'Amico G, Dander E. · · 2022 · cited 23× · PMID 35884364 · DOI 10.3390/cancers14143303

Verify or expand the search:

Other trials of BL-8040

Trials testing the same drug.

Other recruiting trials for T-Acute Lymphoblastic Leukemia

Currently open trials in the same condition.

Other Washington University School of Medicine trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02763384.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing