Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Rare Diseases

Hematologic Neoplasms

Graft vs Host Disease

Hematologic Diseases

Homologous Wasting Disease

Acute Graft Versus Host Disease

All Drugs and Chemicals

Lipid Regulating Agents

Leflunomide

Cholestyramine Resin

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Anticholesteremic Agents

Hypolipidemic Agents

Antimetabolites

Patients receive steroid therapy at the discretion of the treating physician. Beginning within 3 days of starting steroids, patients receive leflunomide PO QD on days 1-28 in the absence of disease progression or unacceptable toxicity. Patients who respond to leflunomide treatment will be tapered off from day 29 until day 56.

Cholestyramine

Steroid Therapy

Monzr M. Al Malki

Monzr M Al Malki

This phase I trial tests the safety and side effects of leflunomide in combination with steroids in treating patients with acute graft versus host disease who have undergone done stem cell transplant for blood cancers (hematologic malignancies). Sometimes the transplanted cells from a donor can attack the body's normal cells (called graft-versus-host disease). Leflunomide and steroids are immunosuppressive drugs that work in different ways to lower the body's immune response so that the new donor immune cells do not attack the body's normal cells. Giving leflunomide in combination with steroids may help treat acute graft versus host disease in patients after stem cell transplant for hematologic malignancies.

PRIMARY OBJECTIVE:

I. Assess the safety and tolerability of leflunomide administration in transplant patients with diagnosis of acute graft-versus-host disease (GvHD) requiring systemic therapy, by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration.

SECONDARY OBJECTIVES:

I. Obtain preliminary evidence of leflunomide activity against acute GvHD by estimating the overall response rate (ORR).

II. Obtain estimates of total steroid dose and length of therapy (area under curve).

III. Day +180 non-relapse mortality (NRM). IV. Overall survival (OS) and progression-free survival (PFS) at one-year. V. Rate and severity of infections during leflunomide administration.

EXPLORATORY OBJECTIVES:

I. Assess the clinical pharmacokinetics of teriflunomide (active metabolite of leflunomide).

II. Assess the presence of and percentage of immune cell subsets (including but not limited to Th17 and regulatory T cells) in blood during leflunomide administration.

III. Assess the changes in presence and levels of GvHD biomarkers and inflammatory cytokines in plasma during the course of treatment with leflunomide.

IV. Obtain a preliminary estimate of gut microbiome diversity at baseline (preferably before leflunomide administration), and then on days +14, +28, and +56.

OUTLINE:

Patients receive steroid therapy at the discretion of the treating physician. Beginning within 3 days of starting steroids, patients receive leflunomide orally (PO) once daily (QD) on days 1-28 in the absence of disease progression or unacceptable toxicity. Patients who respond to leflunomide treatment will be tapered off from day 29 until day 56.

After completion of study treatment, patients are followed up at 28 days, 56 days, 100 days, and 6 months from last dose of leflunomide.

Leflunomide in Combination With Steroids for the Treatment of Acute Graft-versus-Host Disease After Donor Stem Cell Transplant for Hematologic Malignancies

Pilot Trial of Leflunomide in Combination With Steroids for the Treatment of Acute Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies

Toxicity will be graded according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events version 5.0. Unacceptable toxicity (UT) evaluation period will be from starting first loading dose of leflunomide to occurrence of UTs, or stopping leflunomide due to graft versus host disease (GVHD) progression, or day +28, whichever comes first.

Patients who have partial or complete response will be counted as responders. Patients who have stable or progressive disease or withdraw the study early before response assessment is completed will be counted as non-responders.

Will be calculated from day 0 to date of non-disease death from causes other than relapse or progression. Disease relapse/progression will be counted as a competing risk. NRM will be censored at the last follow-up date if patients are alive and free of disease relapse/progression.

FFS will be censored on the last follow-up if patient is still alive and free of any event of interest.

PFS will be censored on the last disease assessment date if patient is still alive and disease relapse/progression is not observed.

The rate of bloodstream infections will be evaluated during leflunomide administration.

The severity of infections will be evaluated during leflunomide administration.

National Cancer Institute (NCI)

City of Hope Medical Center

Heart and Blood Diseases

Symptoms and General Pathology

Multiple Myeloma

Neoplasms, Plasma Cell

Smoldering Multiple Myeloma

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Precancerous Conditions

Hypergammaglobulinemia

Patients receive leflunomide PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Michael A. Rosenzweig

Jeffrey A. Zonder

Saad Usmani, MD

Manisha Bhutani, MD

Michael A Rosenzweig

This phase II trial studies the effects of leflunomide in treating African-American and European-American patients with high-risk smoldering multiple myeloma. Leflunomide is used to decrease the body's immune response and may delay the symptoms of multiple myeloma in patients of African-American and European decent.

PRIMARY OBJECTIVES:

I. To evaluate the anti-myeloma activity of leflunomide, when given as a single agent, as assessed by freedom from progression at 2-years.

II. To evaluate the safety and tolerability of single agent leflunomide.

SECONDARY OBJECTIVES:

I. To summarize and assess toxicities by type, frequency, severity, attribution, time course and duration.

II. To estimate overall and progression-free survival probabilities. III. To estimate response rate and duration of response. IV. To describe the impact of treatment on quality of life, as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score version (v)3.0.

EXPLORATORY OBJECTIVES:

I. To characterize the molecular evolution of the tumor cells. II. To evaluate whether specific genetic subtypes respond differently to leflunomide.

III. To evaluate the role of immune cells in the progression of smoldering multiple myeloma (SMM).

IV. To evaluate the role of leflunomide in modulating the immune system. V. To examine the relationship between immunological changes and disease progression.

OUTLINE:

Patients receive leflunomide orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up yearly.

Leflunomide for the Treatment of High-Risk Smoldering Multiple Myeloma in African-American and European-American Patients

Phase 2 Trial of Leflunomide in African-American and European-American Patients With High-Risk Smoldering Multiple Myeloma

Measured by Common Terminology Criteria for Adverse Events (CTCAE) version (v)5. Will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, serum concentration of the active leflunomide metabolite, probable association with the study treatment and reversibility or outcome.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Leflunomide in Combination With Steroids for the Treatment of Acute Graft-versus-Host Disease After Donor Stem Cell Transplant for Hematologic Malignancies	NCT05443425	Acute Graft Ver... Hematopoietic a...	Cholestyramine Leflunomide Steroid Therapy	18 Years -	City of Hope Medical Center
Leflunomide for the Treatment of High-Risk Smoldering Multiple Myeloma in African-American and European-American Patients	NCT05014646	Smoldering Plas...	Cholestyramine Leflunomide	18 Years -	City of Hope Medical Center
Leflunomide in Combination With Steroids for the Treatment of Acute Graft-versus-Host Disease After Donor Stem Cell Transplant for Hematologic Malignancies	NCT05443425	Acute Graft Ver... Hematopoietic a...	Cholestyramine Leflunomide Steroid Therapy	18 Years -	City of Hope Medical Center

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