What side effects are associated with this type of intervention?

The combination of Pembrolizumab (a PD-1 inhibitor) with GVD chemotherapy for Hodgkin's Lymphoma can lead to a range of side effects. Pembrolizumab is associated with immune-related adverse events such as pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. GVD chemotherapy, which includes gemcitabine, vinorelbine, and doxorubicin, commonly causes myelosuppression, nausea, vomiting, mucositis, and peripheral neuropathy. Patients undergoing this combination therapy may experience overlapping toxicities, requiring careful monitoring and management.

What prior FDA approvals exist?

Pembrolizumab, a PD-1 inhibitor, has been FDA approved for the treatment of relapsed or refractory Hodgkin's Lymphoma. Other PD-1 inhibitors, such as nivolumab, have also received FDA approval for similar indications. These immunotherapies work by blocking the PD-1 pathway, thereby enhancing the immune system's ability to fight cancer. In terms of cytotoxic chemotherapy, agents like doxorubicin, vinblastine, and dacarbazine have been traditionally used in various combinations (e.g., ABVD regimen) for the treatment of Hodgkin's Lymphoma. The combination of pembrolizumab with GVD chemotherapy (gemcitabine, vinorelbine, and doxorubicin) is being studied to evaluate its efficacy and safety in this patient population.

What other types of research exist?

Promising, novel alternatives to Pembrolizumab in combination with GVD chemotherapy for Hodgkin's Lymphoma patients include brentuximab vedotin (BV) combined with AVD (doxorubicin, vinblastine, dacarbazine) and BV combined with nivolumab. These combinations have shown efficacy in clinical studies and may be considered for treatment in 2024.

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Pembrolizumab + GVD for Hodgkin's Lymphoma

Phase 2

Recruiting

Led By Alison Moskowitz, MD

Research Sponsored by Memorial Sloan Kettering Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Have a performance status of 0 or 1 on the ECOG Performance Scale

Be ≥ 18 years of age on day of signing informed consent

Must not have

Received more than 1 prior treatment (combined modality therapy represents 1 treatment) for Hodgkin Lymphoma

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing the combination of pembrolizumab and GVD chemotherapy in patients with Hodgkin lymphoma. Pembrolizumab boosts the immune system to fight cancer, and GVD directly kills cancer cells. Pembrolizumab has shown effectiveness in treating classical Hodgkin lymphoma, especially in patients who have relapsed after initial treatments.

Who is the study for?

Adults with classical Hodgkin's lymphoma that has returned or didn't respond after one multi-agent chemotherapy can join. They must have good heart function, no pregnancy, adequate organ function, and agree to use contraception. Excluded are those with more than one prior treatment, active CNS metastases, certain medical conditions or infections, recent live vaccines, a history of pneumonitis requiring steroids, or an organ transplant.

What is being tested?

The trial is testing the effectiveness and safety of pembrolizumab combined with GVD (gemcitabine, vinorelbine, liposomal doxorubicin) as a second-line treatment for relapsed or refractory Hodgkin lymphoma. Participants will receive this combination therapy to see how well it works compared to previous treatments.

What are the potential side effects?

Possible side effects include reactions related to immune system activation such as inflammation in various organs (like lungs causing pneumonitis), infusion-related reactions from the drugs being administered into the bloodstream and typical chemotherapy-associated effects like fatigue, blood cell count changes leading to increased infection risk.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am fully active or restricted in physically strenuous activity but can do light work.

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I am 18 years old or older.

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My cancer returned or didn't respond after one chemotherapy treatment.

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My cancer came back or didn't respond to treatment, confirmed by a biopsy.

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I have been diagnosed with classical Hodgkin's lymphoma.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had more than one treatment for Hodgkin Lymphoma.

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I have not received a live vaccine within the last 30 days.

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I do not have active HIV, Hepatitis B, or Hepatitis C.

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I haven't needed systemic treatment for an autoimmune disease in the last 2 years.

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I am currently being treated for an infection.

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I have had pneumonitis treated with steroids or have it now.

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I have cancer that has spread to my brain or spinal cord.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Heart rate

Secondary study objectives

Evaluate the 2-year PFS rate (part 2)

Side effects data

From 2024 Phase 3 trial • 453 Patients • NCT03062358

36%

Aspartate aminotransferase increased

30%

Alanine aminotransferase increased

28%

Blood bilirubin increased

21%

Platelet count decreased

18%

Gamma-glutamyltransferase increased

17%

White blood cell count decreased

17%

Pyrexia

16%

Diarrhoea

15%

Anaemia

15%

Decreased appetite

15%

Rash

14%

Blood alkaline phosphatase increased

14%

Neutrophil count decreased

12%

Hypoalbuminaemia

12%

Pruritus

11%

Cough

11%

Upper respiratory tract infection

10%

Proteinuria

10%

Hypothyroidism

10%

Lymphocyte count decreased

Constipation

Arthralgia

Weight decreased

Abdominal pain

Nausea

Bilirubin conjugated increased

Insomnia

Asthenia

Fatigue

Hyperglycaemia

Hypokalaemia

Hyponatraemia

Hypoproteinaemia

Back pain

Hypertension

Vomiting

Abdominal distension

Blood lactate dehydrogenase increased

Hyperthyroidism

Ascites

Abdominal pain upper

Hepatitis B DNA increased

Malaise

Blood glucose increased

Blood creatinine increased

Upper gastrointestinal haemorrhage

Pneumonia

Dyspepsia

Gastrointestinal haemorrhage

Autoimmune hepatitis

Hepatic failure

Hepatitis E

Influenza

Sepsis

Tumour haemorrhage

Hepatic encephalopathy

Pneumonitis

Dysphonia

100%

80%

60%

40%

20%

Study treatment Arm

Pembrolizumab (First Course) + BSC

Placebo + BSC

Pembrolizumab Second Course

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

6Treatment groups

Experimental Treatment

Group I: Safety monitoring beyond after completion of safety window (PART 1)Experimental Treatment5 Interventions

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

Group II: Safety Window and DLT definition (Part 1)Experimental Treatment5 Interventions

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.

Group III: Pembrolizumab maintenance, third-line therapy, and HDT/ASCT (PART 3)Experimental Treatment5 Interventions

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.

Group IV: Pembrolizumab maintenance (PART 2)Experimental Treatment5 Interventions

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.

Group V: Involved-site radiation therapy (ISRT) (PART 3)Experimental Treatment5 Interventions

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

Group VI: Autologous Stem Cell Transplant (ASCT) (PARTS 1 and 3)Experimental Treatment5 Interventions

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

liposomal doxorubicin

2009

Completed Phase 3

~600

gemcitabine

2013

Completed Phase 3

~4260

vinorelbine

2007

Completed Phase 4

~3050

pembrolizumab

2017

Completed Phase 3

~5890

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Hodgkin's Lymphoma include PD-1 inhibitors and cytotoxic chemotherapy. PD-1 inhibitors, such as pembrolizumab, block the PD-1 pathway, which cancer cells use to evade the immune system, thereby enhancing the body's ability to recognize and destroy cancer cells. Cytotoxic chemotherapy agents, like those in the GVD regimen (gemcitabine, vinorelbine, and doxorubicin), work by damaging the DNA of cancer cells, preventing their division and leading to cell death. This combination of immunotherapy and chemotherapy can potentially improve treatment outcomes by utilizing both the immune system's targeting capabilities and the direct cell-killing effects of chemotherapy.