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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

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 CR rate than nelarabine alone without an increase in toxicity and will allow patients to proceed to a potentially curative allogeneic hematopoietic cell transplant.


Detailed Summary:
Sponsor: Washington University School of Medicine

Current Primary Outcome: Safety and tolerability of regimen as measured by frequency and grade of adverse events [ Time Frame: Up to 30 days after completion of treatment (approximately 16 weeks) ]

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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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) ]
  • 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) ]
  • Pharmacodynamic effects of BL-8040 on T-lymphoblasts as measured by induction of apoptosis in lymphoblasts [ Time Frame: Completion of treatment (approximately 12 weeks) ]
  • 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) ]
  • Estimate composite complete remission rate (CRc=CR+CRi) [ Time Frame: 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

  • Estimate overall response rate (CR, CRi + PR) [ Time Frame: 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
    • 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 [ Time Frame: Up to 2 years after completion of treatment (approximately 116 weeks) ]
  • Duration of response [ Time Frame: Up to 2 years after completion of treatment (approximately 116 weeks) ]
    Defined as the interval from the date CR/CRi is documented to the date of recurrence.
  • Disease-free survival [ Time Frame: Up to 2 years after completion of treatment (approximately 116 weeks) ]
    For patients achieving a complete remission, defined as the interval from the date of first documentation of CR/CRi to the date of recurrence or death due to any cause.
  • Event-free survival [ Time Frame: Up to 2 years after completion of treatment (approximately 116 weeks) ]
    Defined as the interval from the date of first dose of study drug to date of treatment failure, recurrence, or death due to any cause.
  • Overall survival [ Time Frame: Up to 2 years after completion of treatment (approximately 116 weeks) ]
    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 [ Time Frame: Completion of treatment (approximately 12 weeks) ]
  • Interaction of pretreatment disease and morphology on clinical outcome [ Time Frame: Up to 2 years after completion of treatment (approximately 116 weeks) ]
  • 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) ]
  • Interaction of pretreatment disease and cytogenetics on clinical outcome [ Time Frame: Up to 2 years after completion of treatment (approximately 116 weeks) ]
  • Interaction of pretreatment disease and immunophenotype on clinical outcome [ Time Frame: Up to 2 years after completion of treatment (approximately 116 weeks) ]
  • 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) ]
  • Same as current

    Information By: Washington University School of Medicine

    Dates:
    Date Received: May 3, 2016
    Date Started: December 2, 2016
    Date Completion: April 30, 2021
    Last Updated: February 2, 2017
    Last Verified: February 2017