First-in-human Study of a New Treatment (4A10) for Patients With Relapsed or Hard-to-treat Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma, Focused on Safety and How the Drug Behaves in the Body and Early Signs of Effect. (ALT-101)
A First in Human, Phase 1, Open-Label Study on the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of 4A10 Monotherapy In Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma
ALT-101 is a first-in-human Phase 1 clinical trial testing a new antibody drug called 4A10 in patients with relapsed or hard-to-treat acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma.
4A10 is a targeted therapy designed to recognize and attach to a specific protein (CD127) found on leukemia cells. Once it binds, it works in two ways: it blocks growth signals that help cancer cells survive, and it helps the immune system find and destroy those cancer cells.
In this study, patients receive 4A10 through an intravenous (IV) infusion once a week. The main goal of the trial is to find out if the drug is safe, what dose can be given, and how the body processes it. Researchers will also look for early signs that the treatment may be working.
The study starts with small groups of patients receiving increasing doses to carefully monitor safety. Each patient is closely observed during the first treatment cycle (about 4-6 weeks) to watch for side effects. If the treatment is helping and is well tolerated, patients may continue treatment for up to six cycles.
Overall, this study is an early step in testing a new, targeted immune-based therapy for difficult-to-treat blood cancers.
Descripción general del estudio
Estado
Intervención / Tratamiento
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 1
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Shibani M Kudchadkar, MD
- Número de teléfono: 15153439875
- Correo electrónico: skudchadkar@allterum.com
Copia de seguridad de contactos de estudio
- Nombre: Yan Moore, MD, MBA
- Número de teléfono: 6178004959
- Correo electrónico: ymoore@allterum.com
Ubicaciones de estudio
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Colorado
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Aurora, Colorado, Estados Unidos, 80045
- Reclutamiento
- Children's Hospital Colorado
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Contacto:
- Kelly Faulk, MD
- Número de teléfono: (720)777-6740
- Correo electrónico: Kelly.Faulk@childrenscolorado.org
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Indiana
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Indianapolis, Indiana, Estados Unidos, 46202
- Reclutamiento
- Riley Children's Hosptial
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Investigador principal:
- Sandeep Batra, MD
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Contacto:
- Sara Quentant
- Número de teléfono: 317-948-3395
- Correo electrónico: squentant@iu.edu
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New York
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New York, New York, Estados Unidos, 10065
- Reclutamiento
- Memorial Sloan Kettering Cancer Center
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Investigador principal:
- Maria Luisa Sulis, MD
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Contacto:
- Juliette Wiseman Site Contact
- Número de teléfono: 855-762-0678
- Correo electrónico: wisemanj@mskcc.org
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Ohio
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Cincinnati, Ohio, Estados Unidos, 45229
- Aún no reclutando
- Cincinnati Children's Hospital Medical Center
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Contacto:
- Lori Backus
- Número de teléfono: 513-636-2047
- Correo electrónico: lori.backus@cchmc.org
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Investigador principal:
- Lauren Pommert, MD
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Pennsylvania
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Philadelphia, Pennsylvania, Estados Unidos, 19104
- Aún no reclutando
- Children's Hospital of Philadelphia
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Contacto:
- Susan Rheingold, MD
- Número de teléfono: (267) 426-0762
- Correo electrónico: rheingold@chop.edu
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Texas
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Fort Worth, Texas, Estados Unidos, 76104
- Reclutamiento
- Cook Children's Medical Center
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Investigador principal:
- Holly Pacenta, MD
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Contacto:
- Heather Jernigan
- Número de teléfono: 682-885-2103
- Correo electrónico: Heather.Jernigan@cookchildrens.org
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Contacto:
- Andrea Martinez
- Número de teléfono: 682-303-3061
- Correo electrónico: andrea.martinez@cookchildrens.org
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Houston, Texas, Estados Unidos, 77030
- Reclutamiento
- Texas Children's Hospital
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Contacto:
- Eric Schafer, MD
- Número de teléfono: (832) 822-3300
- Correo electrónico: esschafe@texaschildrens.org
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Key Inclusion Criteria:
- Confirmed diagnosis of T/B-ALL or T/B-LL
- Relapsed or refractory disease without curative options
- Adequate organ function and performance status
Key Exclusion Criteria:
- Patients with CNS3 disease
- Patients with DNA fragility syndromes (e.g., Fanconi, Bloom), trisomy 21 (Down Syndrome)
- Prior exposure to anti-CD127 therapies
- Uncontrolled infections
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Single Arm
Participants receive 4A10 administered by intravenous route according to the protocol-defined dosing schedule in 28-day cycles until disease progression, unacceptable toxicity, withdrawal of consent, or discontinuation per investigator decision.
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4A10 (Molecule B4532) is an investigational human Immunoglobulin G Subclass 1 (IgG1) monoclonal antibody that specifically binds CD127 (Interleukin-7 receptor alpha subunit, IL-7Rα).
CD127 is a component of the interleukin-7 receptor and the thymic stromal lymphopoietin receptor (TSLPR), which are expressed on T-cell acute lymphoblastic leukemia (T-ALL) and pre-B-cell acute lymphoblastic leukemia (B-ALL) cells.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Incidence of Treatment-Emergent Adverse Events (TEAEs) at each dose level
Periodo de tiempo: Through study duration, an average of 1 year
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Assessment of safety and tolerability of 4A10 as measured by the incidence, severity, and relationship of treatment-emergent adverse events, as graded by CTCAE v6, in participants receiving study treatment at each dose-level in the 3+3 dose escalation study design.
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Through study duration, an average of 1 year
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Determine the Recommended Phase 2 Dose (RP2D)/ Recommended Dose for Expansion (RDE) of 4A10 as a single agent in patients with R/R ALL/LL.
Periodo de tiempo: Through study duration, an average of 1 year
|
Determination of the RP2D/RDE of ALT-101 based on evaluation of safety, tolerability, and available pharmacokinetic and pharmacodynamic data following dose-escalation.
|
Through study duration, an average of 1 year
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Preliminary anti-tumor activity of 4A10 as a single agent in patients with refractory/ relapsed ALL or LL.
Periodo de tiempo: Through study duration, an average of 1 year
|
Complete Remission (CR) Rate Percentage of participants who achieve Complete Remission (CR) according to standardized disease response criteria.
|
Through study duration, an average of 1 year
|
|
Determine the Pharmacokinetics of 4A10 as a single agent in patients with Relapsed/Refractory ALL/LL.
Periodo de tiempo: Through study duration, an average of 1 year
|
Cmax (Maximum Observed Concentration): The highest observed plasma (or serum) concentration of 4A10 following administration. This parameter reflects the peak systemic exposure achieved after dosing. |
Through study duration, an average of 1 year
|
|
Determine the Pharmacokinetics of 4A10 as a single agent in patients with Relapsed/Refractory ALL/LL.
Periodo de tiempo: Through study duration, an average of 1 year
|
Tmax (Time to Maximum Concentration): The time elapsed from 4A10 administration to the occurrence of Cmax. This parameter describes the rate of absorption and systemic exposure onset. |
Through study duration, an average of 1 year
|
|
Determine the Pharmacokinetics of 4A10 as a single agent in patients with Relapsed/Refractory ALL/LL.
Periodo de tiempo: Through the study duration, an average of 1 year.
|
AUC (Area Under the Concentration-Time Curve): The integral of the plasma concentration-time curve over a defined time interval (e.g., AUC₀-t and/or AUC₀-∞), representing the total systemic exposure to 4A10 over time. |
Through the study duration, an average of 1 year.
|
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Determine the Pharmacokinetics of 4A10 as a single agent in patients with Relapsed/Refractory ALL/LL.
Periodo de tiempo: Through the study duration, an average of 1 year
|
T½ (Elimination Half-Life): The time required for the plasma concentration of 4A10 to decrease by 50% during the terminal elimination phase. This parameter reflects the rate of systemic drug elimination. |
Through the study duration, an average of 1 year
|
|
Determine the Pharmacokinetics of 4A10 as a single agent in patients with Relapsed/Refractory ALL/LL.
Periodo de tiempo: Through the study duration, an average of 1 year
|
Vd (Volume of Distribution): A theoretical volume representing the extent to which 4A10 distributes into tissues relative to plasma. It provides insight into the drug's tissue distribution characteristics. |
Through the study duration, an average of 1 year
|
|
Determine the Pharmacokinetics of 4A10 as a single agent in patients with Relapsed/Refractory ALL/LL.
Periodo de tiempo: Through the study duration, an average of 1 year
|
CL (Clearance): The rate at which 4A10 is removed from systemic circulation, typically expressed as volume per unit time. This parameter reflects the efficiency of drug elimination via metabolic and/or excretory pathways. |
Through the study duration, an average of 1 year
|
|
Preliminary anti-tumor activity of 4A10 as a single agent in patients with refractory/ relapsed ALL or LL.
Periodo de tiempo: Through study duration, an average of 1 year.
|
Complete Remission With Incomplete Count Recovery (CRi) Rate Percentage of participants who achieve Complete Remission with Incomplete Count Recovery (CRi) according to standardized disease response criteria.
|
Through study duration, an average of 1 year.
|
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Preliminary anti-tumor activity of 4A10 as a single agent in patients with refractory/ relapsed ALL or LL.
Periodo de tiempo: Through study duration, an average of 1 year
|
Measurable Residual Disease (MRD) Negativity Rate Percentage of participants achieving MRD-negative status among participants who achieve CR or CRi.
|
Through study duration, an average of 1 year
|
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Preliminary anti-tumor activity of 4A10 as a single agent in patients with refractory/ relapsed ALL or LL.
Periodo de tiempo: Through study duration, an average of 1 year
|
Duration of Response (DOR) Time from first documented CR or CRi to disease relapse, progression, or death from any cause, whichever occurs first.
|
Through study duration, an average of 1 year
|
|
Preliminary anti-tumor activity of 4A10 as a single agent in patients with refractory/ relapsed ALL or LL.
Periodo de tiempo: Through study duration, an average of 1 year
|
Time to Response (TTR) Time from initiation of study treatment to first documented achievement of CR or CRi.
|
Through study duration, an average of 1 year
|
|
Preliminary anti-tumor activity of 4A10 as a single agent in patients with refractory/ relapsed ALL or LL.
Periodo de tiempo: Through study duration, an average of 1 year
|
Event-Free Survival (EFS) Time from initiation of study treatment to treatment failure, relapse, or death from any cause.
|
Through study duration, an average of 1 year
|
|
Preliminary anti-tumor activity of 4A10 as a single agent in patients with refractory/ relapsed ALL or LL.
Periodo de tiempo: Through the study duration, an average of 1 year
|
Time to Progression (TTP) Time from initiation of study treatment to documented disease progression.
|
Through the study duration, an average of 1 year
|
|
Preliminary anti-tumor activity of 4A10 as a single agent in patients with refractory/ relapsed ALL or LL
Periodo de tiempo: Through study duration, an average of 1 year
|
Overall Survival (OS) Time from initiation of study treatment to death from any cause.
|
Through study duration, an average of 1 year
|
|
Preliminary anti-tumor activity of 4A10 as a single agent in patients with refractory/ relapsed ALL or LL
Periodo de tiempo: Through study duration, an average of 1 year
|
Rate of Hematopoietic Stem Cell Transplantation (HSCT) Percentage of participants proceeding to hematopoietic stem cell transplantation following study treatment.
|
Through study duration, an average of 1 year
|
|
Preliminary anti-tumor activity of 4A10 as a single agent in patients with refractory/ relapsed ALL or LL
Periodo de tiempo: Through study duration, an average of 1 year
|
Transfusion Independence Rate Percentage of participants achieving transfusion independence during study treatment and follow-up.
|
Through study duration, an average of 1 year
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Silla de estudio: Eric Schafer, MD, Baylor College of Medicine
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Procesos Patológicos
- Neoplasias
- Atributos de la enfermedad
- Enfermedades del sistema inmunológico
- Neoplasias por tipo histológico
- Enfermedades hematológicas
- Enfermedades linfáticas
- Trastornos linfoproliferativos
- Trastornos inmunoproliferativos
- Leucemia Linfoide
- Condiciones Patológicas, Signos y Síntomas
- Enfermedades hemic y linfáticas
- Reaparición
- Leucemia
- Leucemia-linfoma linfoblástico de células precursoras
Otros números de identificación del estudio
- The ALLiance Study
- 5R44CA268530-02 (Subvención/contrato del NIH de EE. UU.)
- DP230071 (Otro número de subvención/financiamiento: Cancer Prevention and Research Institute of Texas (CPRIT))
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Allterum Therapeutics is committed to responsible sharing of clinical trial data in accordance with the recommendations of the International Committee of Medical Journal Editors (ICMJE), applicable laws and regulations, and protection of participant privacy.
Individual participant data (IPD) that underlie the results reported in publications arising from this study, after de-identification, may be made available to qualified researchers upon reasonable request. Supporting documents, including the study protocol, may also be made available, as appropriate.
Data will become available beginning 6 months following publication of the primary study results and may remain available for up to 5 years thereafter. Requests for access must include a scientifically sound research proposal and may be subject to review by the Sponsor. Data will be provided only after execution of an appropriate data sharing agreement.
Marco de tiempo para compartir IPD
Criterios de acceso compartido de IPD
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
Información sobre medicamentos y dispositivos, documentos del estudio
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Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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