ReclutandoNCT03618550Registro de ClinicalTrials.gov

Phase II Study of Second- Line Pembrolizumab Plus GVD for Relapsed or Refractory Hodgkin Lymphoma

Hodgkin Lymphoma · Relapsed or Refractory Hodgkin Lymphoma

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LO ESENCIAL

De qué trata este estudio

El registro indica que este estudio recluta participantes. La disponibilidad puede variar por centro.

Tipo de estudio: De intervención
Fase: Fase 2
Rango de edad: 18 años - No especificado
Sexo admitido: Todos los sexos
Voluntarios sanos: No aceptados
Participantes: 257 Estimado

Estos son puntos de partida, no una decisión de elegibilidad. El equipo debe revisar todos los requisitos.

Las explicaciones y la navegación están en español. Los textos proporcionados por el registro, incluidos títulos, resúmenes y criterios, se conservan en su idioma original. Puedes pedir orientación en español a WCR.

Acerca de la investigación

The purpose of this study is to test any good and bad effects of the study drug, pembrolizumab, in combination with GVD in the treatment of Hodgkin lymphoma.

¿Quién podría participar?

La lista siguiente contiene el texto del patrocinador. Puede incluir condiciones, tratamientos previos, resultados de pruebas y otros requisitos. Aparecer en tu búsqueda no significa que califiques.

Inclusion Criteria:

Histologic diagnosis of classical Hodgkin's lymphoma. Primary refractory or relapsed disease proven by biopsy at enrolling institution.
Be willing and able to provide written informed consent/assent for the trial.
Be ≥ 18 years of age on day of signing informed consent.
PET scan before initiating pembro-GVD have measurable disease based on Lugano 2014 criteria
Have a performance status of 0 or 1 on the ECOG Performance Scale
Demonstrate adequate organ function as defined in table below
Demonstrate adequate organ function as defined in table below. Hematological\*
Absolute neutrophil count (ANC) ≥1000 /mcL
Platelets ≥50,000 / mcL
Hemoglobin ≥8 g/dL Renal
Serum creatinine OR ≤1.5 X upper limit of normal (ULN) OR
Measured or calculated creatinine clearance (eGFR can also be used in place of creatinine) ≥60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN Hepatic\*
Serum total bilirubin ≤ 1.5 X ULN OR ≤ 3 X ULN for subjects with liver metastases
AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases Pulmonary
Hemoglobin-adjusted diffusing capacity for carbon monoxide ≥50% (If unadjusted DLCO is \>/= 50% then there is no need to calculate adjusted) Cardiac
Ejection fraction ≥45% Coagulation
International normalized ratio (INR) OR prothrombin time (PT), Activated partial thromboplastin time (aPTT): ≤ 1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants

\*Lab values for eligibility should be based upon labs prior to Cycle 1 treatment of Pembro-GVD.
* Female subject of childbearing potential should have a negative urine or serum pregnancy within 2 weeks prior to receiving the first dose of study medication. On the day of planned treatment, if a blood pregnancy test has not been performed within the two week window, a stat pregnancy test (urine or blood) should be performed and the results reviewed before treatment is begun.
* Female subjects of childbearing potential must be willing to use an adequate method of contraception (see details in section 11.4.3).
* Male subjects of childbearing potential must agree to use an adequate method of contraception.(see details in section 11.4.3).
* HIV-infected participants must have well-controlled HIV on ART, defined as:

Participants on ART must have a CD4+ T-cell count ≥350 cells/mm3 at the time of screening
Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the LLOQ (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks before screening
It is advised that participants must not have had any AIDS-defining opportunistic infections within the past 12 months.
Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks before study entry (Day 1) and agree to continue ART throughout the study
Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤Grade 2 neuropathy are eligible.

Exclusion Criteria:

Known pregnancy or breast-feeding.

Breast-feeding should be discontinued prior to treatment initiation.
Medical illness unrelated to Hodgkin's Lymphoma, which, in the opinion of the attending physician and/or principal investigator, makes participation in this study inappropriate.
Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
Has known active HIV, Hepatitis B (e.g., Hepatitis B PCR positive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
Has a history of pneumonitis related to PD-1 blockade that required steroids.
Has an active infection requiring systemic therapy.
Has not adequately recovered from major surgery or has ongoing surgical complications
Has undergone solid organ transplant at any time, or prior allogeneic hematopoietic stem cell transplantation within the last 5 years. (Subjects who have had an allogeneic hematopoietic transplant greater than 5 years ago are eligible as long as there are no symptoms of GVHD.)
Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Entiende la evaluación inicial

Tratamiento, grupos y participación

El registro puede describir tratamientos y duración sin incluir un calendario completo. Pide al equipo las visitas, procedimientos, riesgos, costos y alternativas. Mantén tu atención habitual salvo que tu médico te indique un cambio.

Asignación: Sin asignación al azar
Enmascaramiento: Sin enmascaramiento

Safety Window and DLT definition (Part 1)

Initially, 6 patients will be treated on the safety portion of the study and observed for dose limiting toxicities (DLTs). If 1 or fewer patients experience dose\[1\]limiting toxicity (DLT), enrollment onto the study will proceed according to a phase II, Simon 2- stage design.

Drug: pembrolizumab · Drug: gemcitabine · Drug: vinorelbine · Drug: liposomal doxorubicin · Procedure: Stem cell mobilization and collection

Safety monitoring beyond after completion of safety window (PART 1)

During the phase II portion of the study, patients will continue to be monitored for DLTs, adverse events, and events of interest throughout treatment with pembrolizumab-GVD, ASCT (part 1, if applicable), and 100 days following the last dose of pembrolizumab. Total planned enrollment is 39 patients

Drug: pembrolizumab · Drug: gemcitabine · Drug: vinorelbine · Drug: liposomal doxorubicin · Procedure: Stem cell mobilization and collection

Autologous Stem Cell Transplant (ASCT) (PARTS 1 and 3)

Stem cell mobilization and collection will be performed as per institutional guidelines after 2-4 cycles of pembrolizumab-GVD.

Drug: pembrolizumab · Drug: gemcitabine · Drug: vinorelbine · Drug: liposomal doxorubicin · Procedure: Stem cell mobilization and collection

Pembrolizumab maintenance (PART 2)

In part 2 of the study, patients who achieve complete response after 4 cycles of pembrolizumab\[1\]GVD will receive single-agent pembrolizumab for 13 cycles, which will begin 3-5 weeks after cycle 4 of pembrolizumab-GVD.

Drug: pembrolizumab · Drug: gemcitabine · Drug: vinorelbine · Drug: liposomal doxorubicin · Procedure: Stem cell mobilization and collection

Pembrolizumab maintenance, third-line therapy, and HDT/ASCT (PART 3A)

In part 3 of the study, patients who achieve complete response after 2 cycles of pembrolizumab\[1\]GVD will be randomized to either consolidation with autologous stem cell transplant (after an additional optional 1-2 cycles of pembro-GVD) or 2 cycles of pembro-GVD followed by single agent pembrolizumab maintenance for 13 cycles.

Drug: pembrolizumab · Drug: gemcitabine · Drug: vinorelbine · Drug: liposomal doxorubicin · Procedure: Stem cell mobilization and collection

Involved-site radiation therapy (ISRT) (PART 3B)

Patients with limited sites of disease prior to initiation of pembro-GVD are eligible to receive ISRT prior to ASCT with pembrolizumab maintenance.

Drug: pembrolizumab · Drug: gemcitabine · Drug: vinorelbine · Drug: liposomal doxorubicin · Procedure: Stem cell mobilization and collection · Radiation: Involved-site radiation therapy

pembrolizumab DRUG

Age 10-17: 2mg/kg (cap at 200mg), Age ≥ 18: 200 mg (flat) ,Day 1 of each 3 week cycle IV infusion 2-4 cycles (pre-ASCT)

gemcitabine DRUG

1000mg/m\^2 Days 1 and 8 of each 3 week cycle IV infusion 2-4 cycles

vinorelbine DRUG

20mg/m\^2 Days 1 and 8 of each 3 week cycle IV infusion 2-4 cycles

liposomal doxorubicin DRUG

15mg/m\^2 Days 1 and 8 of each 3 week cycle IV infusion 2-4 cycles

Stem cell mobilization and collection PROCEDURE

Stem cell mobilization and collection will be performed as per standard MSKCC guidelines after 2-4 cycles of pembrolizumab-GVD.

Involved-site radiation therapy RADIATION

Involved-site radiation therapy (ISRT) Patients with limited sites of disease prior to initiation of pembro-GVD are eligible to receive ISRT prior to ASCT or with pembrolizumab maintenance. n. ISRT to nodal based disease should be delivered in line with the guidelines provided by the International Lymphoma Radiation Oncology Group.

Prepara tus preguntas

Qué evalúan los investigadores

Estas medidas indican qué se estudia. No prueban que un tratamiento funcione.

Medidas principales

Complete response rate (part 1)

Plazo: 2 years

Response to pembrolizumab-GVD will be assessed using the RECIL criteria.

Assess freedom from disease at 5 years (part 3)

Plazo: 5 years

A disease event will be defined as disease relapse after transplant or after maintenance if transplant does not occur, death, or loss to follow-up before the 5-year follow-up period ends.

Medidas secundarias

Evaluate the 2-year PFS rate (part 2)

Plazo: 2 years

Only patients who receive the Pembrolizumab maintenance regime will be considered evaluable for 2-year PFS and OS rates.

El registro no indica resultados publicados.

Revisa las tablas completas y sus limitaciones en el registro oficial.

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Centros de investigación (10)

El estado general puede diferir del estado de un centro. Confirma la disponibilidad antes de trasladarte.

Buscar un centro en este estudio

10 centros

City of Hope Cancer CenterDuarte, California, United StatesReclutando

Matthew Mei, MDCONTACT626-275-8064

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Stanford University Medical CenterStanford, California, United StatesReclutando

Ranjana Advani, MDCONTACT650-498-6000

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University of MiamiMiami, Florida, United StatesReclutando

Craig Moskowitz, MDCONTACT305-243-5302

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Memorial Sloan Kettering Basking RidgeBasking Ridge, New Jersey, United StatesReclutando