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

NCT02763384 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2016061462P50CA171963-06
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

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.

Conditions

T-Acute Lymphoblastic Leukemia; Adult T Lymphoblastic Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 30 days after completion of treatment (median follow-up of 51.5 days, full range 24-120 days)

Secondary Outcomes (7)

• Composite Complete Remission Rate (CRc=CR+CRi)

  Completion of treatment (approximately 12 weeks)

• Overall Response Rate (CR, CRi + PR)

  Through completion of treatment (median treatment length of 37.5 days, full range of 13-90 days)

• Time to Response

  Through completion of treatment (median treatment length of 37.5 days, full range of 13-90 days)

• Duration of Response

  Through date of recurrence or completion of follow-up (maximum of 2 years after completion of treatment)

• Event-free Survival (EFS)

  Through completion of follow-up (maximum of 2 years after completion of treatment)

Other Outcomes (10)

• 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 Performance Status on Clinical Outcome

  Up to 2 years after completion of treatment (approximately 116 weeks)

• Interaction of Pretreatment Disease and Immunophenotype on Clinical Outcome

  Up to 2 years after completion of treatment (approximately 116 weeks)

Study Arms (1)

Arm 1: BL-8040 and Nelarabine

EXPERIMENTAL

* 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

Drug: BL-8040; Drug: Nelarabine

Interventions

BL-8040 DRUG

Arm 1: BL-8040 and Nelarabine

Nelarabine DRUG

Also known as: Arranon

Arm 1: BL-8040 and Nelarabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• The Leukemia and Lymphoma Society: collaborator
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Interventions

4-fluorobenzoyl-TN-14003; nelarabine

Condition Hierarchy (Ancestors)

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Geoffrey L. Uy, M.D.
• Organization: Washington University School of Medicine

guy@wustl.edu

314-747-8439

Study Officials

• Geoffrey L Uy, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2016
• First Posted: May 5, 2016
• Study Start: December 2, 2016
• Primary Completion: February 11, 2022
• Study Completion: May 22, 2022
• Last Updated: October 31, 2023
• Results First Posted: October 31, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)