Trial of LAVA-051 in Patients With Relapsed/Refractory CLL, MM, or AML

Multiple Myeloma Clinical Trial

Official title:

A Phase 1/2a 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04887259
• Other study ID #: LV2020-001
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: July 12, 2021
• Est. completion date: December 30, 2024

Study information

• Verified date: June 2023
• Source: Lava Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A phase 1/2a, 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).

Description:

An open-label, phase 1/2a 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 102
• Est. completion date: December 30, 2024
• Est. primary completion date: September 24, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Multiple Myeloma

Intervention

Biological:
• LAVA-051
In part 1 and part 2, LAVA-051 will be administered via intravenous (IV) infusion
• Interleukin 2
In Part 1 and Part 2, a low dose of interleukin 2 will be given via subcutaneous injection with LAVA-051 in a selected group of patients

Locations

Country	Name	City	State
France	CHU Lille	Lille
France	University Hospital of Nantes	Nantes
Netherlands	Amsterdam UMC, location AMC	Amsterdam	Noord Holland
Netherlands	Amsterdam UMC, location VUmc	Amsterdam	Noord-Holland
Netherlands	Erasmus MC	Rotterdam	Zuid-Holland
Spain	University Hospital Vall d'Hebron	Barcelona
Spain	Cima University of Navarra	Madrid
Spain	Clinica Universida de Navarra	Pamplona
Spain	Hospital Clinico Universitario de Salamanca	Salamanca
United States	Emory Winship Cancer Institute	Atlanta	Georgia
United States	Levine Cancer Institute, Atrium Health	Charlotte	North Carolina
United States	Cleveland Clinic	Cleveland	Ohio
United States	MD Anderson Cancer Center	Houston	Texas
United States	NYU Langone Health	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Lava Therapeutics

Countries where clinical trial is conducted

United States,  France,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1 & Part 2 - Frequency and severity of AEs:	Frequency, severity, and grading of Adverse Events using the Common Terminology Criteria and grading for Adverse Events (CTCAE) v5.0. CRS will be evaluated using the ASTCT.	Approximately 6 months
Primary	Part 1 - Frequency and type of DLT	A DLT is defined as an adverse event that is unrelated to disease progression, intercurrent illness, or concomitant medications and is occurring during the first 28 days of treatment. These events will be classified according to the CTCAE v5.0; CRS will be evaluated according to the ASTCT consensus criteria	First 28 days of treatment
Secondary	Part 1 & Part 2: Number of participants with an antitumor response	Antitumor response for CLL per iwCLL guidelines, MM per IMWG-based response criteria, and AML per ELN criteria	Approximately 6 months
Secondary	Part 1 & Part 2: Pharmacokinetics of LAVA-051, area under the plasma concentration versus time curve (AUC)	Area under the plasma concentration versus time curve (AUC) of LAVA-051 will be assessed in all patients treated with LAVA-051	Approximately 6 months
Secondary	Part 1 & Part 2: Incidence and prevalence anti-LAVA-051 antibodies	Development of antibodies (anti-drug antibodies) to LAVA-051 will be evaluated	Approximately 6 months