Symptoms and General Pathology

All Conditions

Nutritional and Metabolic Diseases

Neoplasms

Immune System Diseases

Blood and Lymph Conditions

Rare Diseases

Recurrence

Amyloidosis

Immunoglobulin Light-chain Amyloidosis

Proteostasis Deficiencies

Metabolic Diseases

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Immunoproliferative Disorders

Paraproteinemias

AL Amyloidosis

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Antirheumatic Agents

Dermatologic Agents

Anti-Infective Agents

Dexamethasone

Cyclophosphamide

Lenalidomide

Dexamethasone acetate

BB 1101

Elotuzumab

Ichthammol

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Angiogenesis Inhibitors

Growth Inhibitors

HIV Protease Inhibitors

Protease Inhibitors

Enzyme Inhibitors

Patients receive lenalidomide PO on days 1-21 and dexamethasone IV on days 1, 8, 15, and 22. Patients also receive elotuzumab IV over 1 hour on days 1, 8, 15, and 22 of courses 1 and 2 and days 1 and 15 of subsequent courses. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive lenalidomide PO on days 1-21 and dexamethasone IV on days 1, 8, 15, and 22. Patients also receive elotuzumab IV over 1 hour on day 1. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Patients receive lenalidomide, dexamethasone, and elotuzumab as in Arm I. Patients also receive cyclophosphamide IV on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive lenalidomide PO on days 1-21 and dexamethasone IV on days 1, 8, 15, and 22. Patients also receive elotuzumab IV over 1 hour on day 1. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Pharmacological Study

Jeffrey Zonder, M.D.

This randomized phase II trial studies how well lenalidomide, dexamethasone, and eotuzumab with or without cyclophosphamide work in treating patients with primary amyloidosis that has come back after a period of improvement. Drugs used in chemotherapy, such as lenalidomide, dexamethasone, and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as eotuzumab, may interfere with the ability of cancer cells to grow and spread. Giving lenalidomide, dexamethasone, and eotuzumab with cyclophosphamide may work better in treating patients with primary amyloidosis.

PRIMARY OBJECTIVES:

I. To assess the rate of hematologic response of very good partial response (VGPR) or better according to the International Society of Amyloidosis (ISA) hematologic response criteria.

SECONDARY OBJECTIVES:

I. To assess duration of hematologic response. II. To assess time to hematologic progression. III. To assess overall hematologic response rate. IV. To assess complete hematologic response rate. V. To assess organ response (according to ISA organ response criteria). VI. To assess overall survival (OS).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive lenalidomide orally (PO) on days 1-21 and dexamethasone intravenously (IV) on days 1, 8, 15, and 22. Patients also receive elotuzumab IV over 1 hour on days 1, 8, 15, and 22 of courses 1 and 2 and days 1 and 15 of subsequent courses. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive lenalidomide, dexamethasone, and elotuzumab as in Arm I. Patients also receive cyclophosphamide IV on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: All patients receive lenalidomide PO on days 1-21 and dexamethasone IV on days 1, 8, 15, and 22. Patients also receive elotuzumab IV over 1 hour on day 1. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 24 months.

Lenalidomide, Dexamethasone, and Elotuzumab With or Without Cyclophosphamide in Treating Patients With Relapsed Primary Amyloidosis

A Randomized Phase 2 Trial of Lenalidomide/ Dexamethasone/ Elotuzumab +/- Cyclophosphamide Followed by Lenalidomide/ Dexamethasone/Elotuzumab Maintenance as Second-Line Therapy for Patients With Relapsed AL Amyloidosis

Will be expressed as a proportion with Clopper-Pearson exact 95% confidence intervals.

Will be reported with descriptive statistics including 95% confidence intervals.

Will be reported with descriptive statistics including 95% confidence intervals and will be estimated using Kaplan-Meier methods for median time to event data and 95% confidence intervals.

Will be assessed by the investigator and reported in the electronic case report form and reported with descriptive statistics including 95% confidence intervals.

National Cancer Institute (NCI)

Bristol-Myers Squibb

Multiple Myeloma Research Consortium

Barbara Ann Karmanos Cancer Institute

Principal Investigator

Digestive System Diseases

Mouth and Tooth Diseases

Heart and Blood Diseases

Hemorrhage

Constipation

Diarrhea

Lymphadenopathy

Nausea

Gastrointestinal Hemorrhage

Purpura

Hepatomegaly

Macroglossia

Signs and Symptoms, Digestive

Hemostatic Disorders

Blood Coagulation Disorders

Hematologic Diseases

Skin Manifestations

Lymphatic Diseases

Gastrointestinal Diseases

Liver Diseases

Hypertrophy

Pathological Conditions, Anatomical

Tongue Diseases

Mouth Diseases

Stomatognathic Diseases

Hypoglycemic Agents

Gliclazide

Patients receive isatuximab IV on days 1, 8, 15, and 22 of course 1 and on days 1 and 15 of subsequent courses. Treatment repeats every 28 days for 24 courses in the absence of disease progression or unacceptable toxicity.

Isatuximab

Emma Scott

This phase II trial studies how well isatuximab works in treating patients with primary amyloidosis that has come back or does not respond to treatment. Monoclonal antibodies, such as isatuximab, may interfere with the ability of cancer cells to grow and spread.

PRIMARY OBJECTIVES:

I. To assess the efficacy as measured by the confirmed overall hematologic response rate (partial response or better) of isatuximab in relapsed/refractory systemic light chain (AL) amyloidosis.

SECONDARY OBJECTIVES:

I. To evaluate toxicities in the treatment of relapsed/refractory AL amyloidosis with isatuximab.

II. To evaluate time to hematologic response. III. To evaluate duration of response. IV. To evaluate progression-free survival (PFS). V. To evaluate overall survival (OS).

TERTIARY OBJECTIVES:

I. To evaluate efficacy of isatuximab in relapsed/refractory immunoglobulin amyloid light chain (AL) amyloidosis as measured by organ specific response rates (cardiac, renal, gastrointestinal \[GI\], liver, soft tissue, nerve), in the subset of patients that can be evaluated for organ response.

II. To evaluate time to organ response in the subset of patients that can be evaluated for organ response.

OUTLINE:

Patients receive isatuximab intravenously (IV) on days 1, 8, 15, and 22 of course 1 and on days 1 and 15 of subsequent courses. Treatment repeats every 28 days for 24 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up within 30 days and then every at least every 6 months for up to 4 years.

S1702 Isatuximab in Treating Patients With Relapsed or Refractory Primary Amyloidosis

A Phase II Study of Isatuximab (SAR650984) (NSC-795145) for Patients With Previously Treated AL Amyloidosis

Will include partial response, very good partial response and complete response. Hematologic response will be reported with a binomial confidence interval.

Will be evaluated using the Common Terminology Criteria for Adverse Events version 4.0. The maximum grade for each toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.

Organ response will be evaluated in the subset of patients with evaluable organ involvement using current criteria. The proportion of patients with organ response will be estimated as the number of patients with documented organ response out of the number of patients with documented evaluable organ involvement at baseline.

Will be estimated using the Kaplan-Meier method.

SWOG Cancer Research Network

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Lenalidomide, Dexamethasone, and Elotuzumab With or Without Cyclophosphamide in Treating Patients With Relapsed Primary Amyloidosis	NCT03252600	Recurrent Prima...	Cyclophosphamid... Dexamethasone Elotuzumab Laboratory Biom... Lenalidomide Pharmacological...	18 Years -	Barbara Ann Karmanos Cancer Institute
S1702 Isatuximab in Treating Patients With Relapsed or Refractory Primary Amyloidosis	NCT03499808	Amorphous, Eosi... Constipation Diarrhea Early Satiety Gastrointestina... Hepatomegaly Lymphadenopathy Macroglossia Nausea Primary Systemi... Purpura Recurrent Prima... Refractory Prim...	Isatuximab Laboratory Biom...	18 Years -	SWOG Cancer Research Network

Spots Global Cancer Trial Database for recurrent primary amyloidosis