Infections

All Conditions

Symptoms and General Pathology

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Recurrence

Communicable Diseases

Lymphoma

Acquired Immunodeficiency Syndrome

HIV Infections

Hodgkin Disease

Lymphoma, AIDS-Related

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Disease Attributes

Lymphoma, B-Cell

Lymphosarcoma

Hodgkin Lymphoma

Lymphoma AIDS Related

B-cell Lymphoma

CONDITIONING: Patients undergo high-dose chemotherapy or chemoradiotherapy according to institutional guidelines.

STEM CELL INFUSION: Patients undergo hematopoietic stem cell transplant on day 0.

Note: Patients continue to receive HAART throughout treatment, with a 7-day break for apheresis. Patients may be eligible for a structured treatment interruption of up to 12 weeks after autologous hematopoietic stem cell transplant with gene-modified cells.

Receive LVsh5/C46 (Cal-1) transduced CD34+ HSPC IV

Gene-Modified HIV-Protected Hematopoietic Stem Cells

Laboratory Biomarker Analysis

Undergo high-dose chemotherapy or chemoradiotherapy

Transplant Conditioning

Hans-Peter Kiem

This clinical trial studies gene-modified, human immunodeficiency virus (HIV)-protected stem cell transplant in treating patients with HIV-associated lymphoma. Stem cells, or cells which help form blood, are collected from the patient and stored. They are treated in the laboratory to help protect the immune system from HIV. Chemotherapy is given before transplant to kill lymphoma cells and to make room for new stem cells to grow. Patients then receive the stem cells that were collected from them before chemotherapy and have been genetically modified to replace the stem cells killed by the chemotherapy.

PRIMARY OBJECTIVES:

I. To assess the safety and feasibility of infusing gene-modified, HIV-protected hematopoietic stem/progenitor cells (HSPC) after high-dose chemotherapy for treatment of acquired immune deficiency syndrome (AIDS)-related lymphoma.

II. To observe the change in gene-modified cell levels before and after antiviral treatment interruption.

SECONDARY OBJECTIVES:

I. To evaluate the molecular and clonal composition of gene-modified cells after hematopoietic cell transplant (HCT).

II. To describe time to disease progression, progression-free survival, treatment-related mortality, time to neutrophil and platelet recovery, and incidence of infections.

TERTIARY OBJECTIVES:

I. To evaluate the effect of procedure on HIV-specific immune reconstitution.

II. To observe the effect of HIV infection on the presence of gene-marked cells as determined by deoxyribonucleic (DNA) polymerase chain reaction (PCR).

OUTLINE:

CONDITIONING: Patients undergo high-dose chemotherapy or chemoradiotherapy according to institutional guidelines.

STEM CELL INFUSION: Patients undergo hematopoietic stem cell transplant with LVsh5/C46 (Cal-1) transduced autologous CD34+ hematopoietic stem/progenitor cells (HSPC) on day 0.

Note: Patients continue to receive highly active antiretroviral therapy (HAART) throughout treatment, with a 7-day break for apheresis. Patients may be eligible for a structured treatment interruption of up to 12 weeks after autologous hematopoietic stem cell transplant with gene-modified cells.

After completion of study treatment, patients are followed up periodically for 2 years, every 6 months for 3 years, and then annually for 15 years post-HCT.

Gene-Modified HIV-Protected Stem Cell Transplant in Treating Patients With HIV-Associated Lymphoma

Autologous Transplantation and Stem Cell-Based Gene Therapy With LVsh5/C46 (CAL-1), a Dual Anti-HIV Lentiviral Vector, for the Treatment of HIV-Associated Lymphoma

Characterized if clinical symptoms suggest clonal expansion of the HSPC or if molecular assays result in clonal expansion in \> 20% of gene-marked cells.

National Cancer Institute (NCI)

Fred Hutchinson Cancer Center

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Dermatologic Agents

Anti-Infective Agents

Gemcitabine

Pembrolizumab

Carboplatin

Antibodies

Antibodies, Monoclonal

Etoposide

Vinorelbine

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Immune Checkpoint Inhibitors

Bendamustine Hydrochloride

Ifosfamide

Etoposide phosphate

Podophyllotoxin

Immunoglobulins

Brentuximab Vedotin

Isophosphamide mustard

Mechlorethamine

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Immunoconjugates

Immunologic Factors

Antimetabolites

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunotoxins

Keratolytic Agents

SALVAGE THERAPY: Patients receive 1 of 3 chemotherapy regimens as clinically indicated: 1) ifosfamide IV, carboplatin IV, and etoposide IV; 2) gemcitabine IV, vinorelbine IV, and pegylated liposomal doxorubicin IV; or 3) brentuximab vedotin IV and bendamustine IV. Patients then undergo a PET/CT scan. Patients who achieve a CR or PR proceed to HDT-ASCT. Patients who achieve SD or PD come off study treatment.

HDT-ASCT: Patients undergo ASCT. Patients may also receive a standard preparative chemotherapy regimen as clinically indicated. Patients who achieve PR prior to ASCT may also undergo RT as clinically indicated. Patients who went into ASCT with PR also undergo a PET/CT scan 30 days post-transplant.

MAINTENANCE THERAPY: Patients may receive brentuximab vedotin IV as clinically indicated.

SALVAGE THERAPY: Patients receive pembrolizumab IV plus 1 of 3 chemotherapy regimens specified in Arm A as clinically indicated. Patients then undergo a PET scan. Patients who achieve a CR or PR proceed to HDT-ASCT. Patients who achieve SD or PD come off study treatment.

HDT-ASCT: Patients undergo ASCT. Patients may also receive a standard preparative chemotherapy regimen as clinically indicated. Patients who achieve PR prior to ASCT may also undergo RT as clinically indicated. Patients who went into ASCT with PR also undergo a PET/CT scan 30 days post-transplant.

MAINTENANCE THERAPY: Patients may receive brentuximab vedotin IV as clinically indicated.

Autologous Hematopoietic Stem Cell Transplantation

Bendamustine

Computed Tomography

Pegylated Liposomal Doxorubicin Hydrochloride

Positron Emission Tomography

Radiation Therapy

Receive standard preparative chemotherapy regimen

Vaishalee P Kenkre

This phase III trial compares chemotherapy versus an immune checkpoint inhibitor drug called pembrolizumab plus chemotherapy in treating patients with classical Hodgkin lymphoma that has come back (relapsed) or that does not respond to treatment (refractory). The usual approach for patients with classical Hodgkin lymphoma is treatment with standard chemotherapy, including drugs that are Food and Drug Administration (FDA)-approved. If this treatment puts a patient into remission, high dose chemotherapy and stem cell transplant may be used to increase the likelihood of a cure. Hodgkin lymphoma is capable of inhibiting the immune system from killing it. Pembrolizumab is a checkpoint inhibitor that may be able to stop this inhibition, allowing the immune system to attack the lymphoma.

PRIMARY OBJECTIVE:

I. To assess the 2-year event free survival (EFS) of patients treated with pembrolizumab added to chemotherapy versus chemotherapy alone, in patients with relapsed/refractory (R/R) classical Hodgkin's lymphoma (cHL) who are intended to receive salvage therapy followed by high dose chemotherapy and autologous stem cell transplant (HDT-ASCT).

PRIMARY IMAGING OBJECTIVE:

I. To assess the diagnostic performance of baseline total metabolic tumor volume (TMTV) in predicting response (complete remission \[CR\] + partial remission \[PR\] versus \[vs\] no response) at pre-transplant/post-salvage for each arm separately and overall.

SECONDARY OBJECTIVES:

I. To assess the 2-year progression free survival (PFS) and overall survival (OS) in the transplanted population.

II. To assess the complete remission (CR) rate to salvage therapy. III. To assess the CR rate post HDT-ASCT. IV. To assess the post HDT-ASCT partial remission (PR) to CR conversion rate.

SECONDARY IMAGING OBJECTIVES:

I. To assess the % change in TMTV (delta TMTV) from baseline to pre-transplant/post-salvage in predicting response (CR+PR vs no response) at pre-transplant/post-salvage for each arm separately and overall.

II. To assess baseline TMTV and delta TMTV in predicting EFS/OS for each arm separately and overall.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A:

SALVAGE THERAPY: Patients receive 1 of 3 chemotherapy regimens as clinically indicated: 1) ifosfamide intravenously (IV), carboplatin IV, and etoposide IV; 2) gemcitabine IV, vinorelbine IV, and pegylated liposomal doxorubicin IV; or 3) brentuximab vedotin IV and bendamustine IV. Patients then undergo a positron emission tomography (PET)/computed tomography (CT) scan. Patients who achieve a CR or PR proceed to HDT-ASCT. Patients who achieve stable disease (SD) or progressive disease (PD) come off study treatment.

HDT-ASCT: Patients undergo ASCT. Patients may also receive a standard preparative chemotherapy regimen as clinically indicated. Patients who achieve PR prior to ASCT may also undergo radiation therapy (RT) as clinically indicated. Patients who went into ASCT with PR also undergo a PET/CT scan 30 days post-transplant.

MAINTENANCE THERAPY: Patients may receive brentuximab vedotin IV as clinically indicated.

ARM B:

SALVAGE THERAPY: Patients receive pembrolizumab IV plus 1 of 3 chemotherapy regimens specified in Arm A as clinically indicated. Patients then undergo a PET scan. Patients who achieve a CR or PR proceed to HDT-ASCT. Patients who achieve SD or PD come off study treatment.

HDT-ASCT: Patients undergo ASCT. Patients may also receive a standard preparative chemotherapy regimen as clinically indicated. Patients who achieve PR prior to ASCT may also undergo RT as clinically indicated. Patients who went into ASCT with PR also undergo a PET/CT scan 30 days post-transplant.

MAINTENANCE THERAPY: Patients may receive brentuximab vedotin IV as clinically indicated.

All patients undergo CT scans during follow-up.

A Trial Comparing Chemotherapy Versus Novel Immune Checkpoint Inhibitor (Pembrolizumab) Plus Chemotherapy in Treating Relapsed/Refractory Classical Hodgkin Lymphoma

Randomized Phase III Trial of Chemotherapy vs. Pembrolizumab Plus Chemotherapy for Relapsed/Refractory Classical Hodgkin Lymphoma

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Events include: failure to achieve partial remission (PR) or complete remission (CR) to salvage chemotherapy, failure to achieve a CR post high dose chemotherapy and autologous stem cell transplant (HDT-ASCT), progression, receipt of unplanned radiation or brentuximab vedotin maintenance, or death. Patients who have not experienced any of these events will be censored at the date they are last known to be progression free. Kaplan-Meier method will be used to estimate EFS, including medians and confidence intervals. Comparison of EFS between treatment arms will be conducted based on intent-to-treat principle using a one-sided stratified log-rank test with the stratification factors.

Will be assessed using positron emission tomography/computed tomography (PET/CT) scan with Deauville score. Will assess the diagnostic performance of baseline metabolic tumor volume (TMTV) in predicting response (CR+PR vs no response) at pre-transplant/post-salvage, overall and by study arm. Diagnostic performance of baseline TMTV will be assessed using area under the receiver operator characteristic curve (ROC AUC) analysis, where the reference standard is pre-transplant/post-salvage response (CR/PR).

Similar methods will be used as the primary imaging aim to assess the diagnostic performance of delta TMTV in predicting pre-transplant/post-salvage response (CR+PR vs no response). Delta TMTV will be defined as the percent change from baseline to pre-transplant/post-salvage \[(post-salvage/pre-transplant - baseline)/baseline X 100\].

Will assess baseline TMTV and delta TMTV in predicting EFS/overall survival (OS) for each arm separately and overall. The association between TMTV and EFS will be analyzed through a Cox regression model. TMTV will be analyzed individually as its absolute value and the percent change from baseline. We will also test if there is a difference by arm by including an interaction term in the model between TMTV and arm. The Kaplan-Meier method will be used to estimate EFS, including median survival times and confidence intervals. In addition to examining the TMTV, we will also analyze standard uptake value maximum (SUVmax) and total lesion glycolysis (TLG) with the same methods. The OS outcome will be analyzed in a similar manner.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Gene-Modified HIV-Protected Stem Cell Transplant in Treating Patients With HIV-Associated Lymphoma	NCT02378922	AIDS-Related Ho... AIDS-Related No... HIV Infection Recurrent Hodgk... Recurrent Non-H...	Gene-Modified H... Laboratory Biom... Transplant Cond...	18 Years - 66 Years	Fred Hutchinson Cancer Center
A Trial Comparing Chemotherapy Versus Novel Immune Checkpoint Inhibitor (Pembrolizumab) Plus Chemotherapy in Treating Relapsed/Refractory Classical Hodgkin Lymphoma	NCT05711628	Recurrent Class... Refractory Clas...	Autologous Hema... Bendamustine Brentuximab Ved... Carboplatin Computed Tomogr... Etoposide Gemcitabine Ifosfamide Pegylated Lipos... Pembrolizumab Positron Emissi... Radiation Thera... Transplant Cond... Vinorelbine	5 Years - 75 Years	National Cancer Institute (NCI)
Gene-Modified HIV-Protected Stem Cell Transplant in Treating Patients With HIV-Associated Lymphoma	NCT02378922	AIDS-Related Ho... AIDS-Related No... HIV Infection Recurrent Hodgk... Recurrent Non-H...	Gene-Modified H... Laboratory Biom... Transplant Cond...	18 Years - 66 Years	Fred Hutchinson Cancer Center

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