Clinical trial NCT04887259: Trial of LAVA-051 in Patients with Relapsed/refractory CLL, MM, or AML
Official title: A Phase 1 Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Antitumor Activity of LAVA-051 in Patients with Relapsed or Refractory CLL, MM, or AML
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Chronic Lymphocytic Leukemia
Multiple Myeloma
Acute Myeloid Leukemia
Keywords: CLL
Phase 1 dose escalation
Phase 1 safety
Open label
MM
AML
relapsed
refractory
Lead sponsor: Lava Therapeutics
Sponsor class: INDUSTRY
First posted: 2021-05-14
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: A phase 1, first-in-human trial to evaluate the safety and tolerability of LAVA-051 in patients with relapsed or refractory Chronic Lymphocytic Leukemia (CLL), Multiple Myeloma (MM), or Acute Myeloid Leukemia (AML).

Detailed description: An open-label, phase 1 dose escalation trial with disease-specific expansion cohorts to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary anti-tumor activity of LAVA-051 in patients with relapsed or refractory CLL, MM, or AML.

The trial was intended to be a Phase 1/2 trial (but the trial never moved forward to Phase 2).

Eligibility criteria: KEY INCLUSION CRITERIA

1. Patient must be 18 years of age inclusive or above at the time of signing the informed consent.
2. Patients with documented diagnosis of relapsed or refractory CLL, MM, or AML who have failed to respond to or who have relapsed after prior therapy and are not amenable to standard treatments or for whom no standard treatments are available.
3. Predicated life expectancy of ≥ 3 months.
4. ECOG performance status of 0 or 1.
5. Males or non-pregnant, non-breastfeeding females who are either:

   1. Surgically sterile.
   2. Female of childbearing potential with a negative pregnancy test and compliant with an effective contraceptive regimen.
   3. Female, postmenopausal.
   4. Male compliant with an effective contraceptive regimen.
   5. Male refraining from donating sperm.
6. Capable of giving signed and dated informed consent prior to initiation of any trial-related procedures.

KEY EXCLUSION CRITERIA

1. Prior allogeneic bone marrow transplant if the patient still has active acute or chronic graft versus host disease requiring \>10 mg prednisone or equivalent corticosteroids.
2. Concomitant malignancies except carcinoma in situ, basal or squamous cell skin carcinoma. Patients who had no evidence of disease from another primary cancer for 2 or more years are allowed to participate in the trial. Localized non-metastatic prostate cancer, not requiring systemic treatment, and for which no local treatment is planned, is allowed.
3. Uncontrolled or severe intercurrent medical condition.
4. Previous treatment with an aminobisphonsphonate IV (e.g. ibandronate, pamidronate, zoledronate) within 4 weeks prior to initial IMP administration.
5. Known ongoing drug or alcohol abuse in the opinion of the investigator.
6. Previous autologous haematopoietic stem cell transplantation (HSCT) or treatment with Chimeric Antigen Receptor (CAR) T-cell therapy within 6 months prior to initial IMP administration.
7. Immunodeficiency disorders.
8. Patients with Richter's transformation are excluded.

Other eligibility criteria will apply during full screening.

Primary outcomes:
measure: Part 1 & Part 2 - Frequency and severity of AEs:
timeFrame: Approximately 6 months
measure: Part 1 - Frequency and type of DLT
timeFrame: First 28 days of treatment
Secondary outcomes:
measure: Part 1 & Part 2: Number of participants with an antitumor response
timeFrame: Approximately 6 months
measure: Part 1 & Part 2: Pharmacokinetics of LAVA-051, area under the plasma concentration versus time curve (AUC)
timeFrame: Approximately 6 months
measure: Part 1 & Part 2: Incidence and prevalence anti-LAVA-051 antibodies
timeFrame: Approximately 6 months
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory Winship Cancer Institute
state: Georgia
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute, Atrium Health
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Lille
country: France
facility: CHU Lille
city: Nantes
country: France
facility: University Hospital of Nantes
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, location AMC
state: Noord Holland
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, location VUmc
state: Noord-Holland
city: Rotterdam
country: Netherlands
facility: Erasmus MC
state: Zuid-Holland
city: Barcelona
country: Spain
facility: University Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: Cima University of Navarra
city: Pamplona
country: Spain
facility: Clinica Universida de Navarra
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
Study officials:
affiliation: Lava Therapeutics
name: Clinical Trials Management
role: STUDY_DIRECTOR
References: