Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Light Chain Deposition Disease

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Melphalan

Lenograstim

Immunoglobulins

Immunoglobulins, Intravenous

Myeloma Proteins

Paraproteins

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Mobilization with Filgrastim Stem Cell Transplant Melphalan Conditioning Stem Cell infusion

16 mcg/kg daily beginning 3 days prior to SCC through day before final SCC

filgrastim

70-100 mg/m2/day will be administered intravenously on Days -3 and -2

melphalan

infusion of previously collected stem cells on Day 0

Stem Cell Infusion

Vaishali Sanchorawala, MD

RATIONALE: Giving chemotherapy before a stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as G-CSF, and certain chemotherapy drugs, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.

PURPOSE: This phase II trial is studying the side effects of high-dose melphalan given together with stem cell transplant and to see how well it works in treating patients with immunoglobulin deposition disease or light-chain deposition disease.

OBJECTIVES:

* To assess the tolerability of high-dose melphalan and autologous stem cell transplantation in patients with immunoglobulin deposition disease or light-chain deposition disease.
* To determine the hematologic response rate in patients treated with this regimen.
* To determine the predictability of early free light-chain response for heme response in patients treated with this regimen.
* To determine organ or clinical response in patients treated with this regimen.
* To determine overall survival of these patients.

OUTLINE:

* Stem cell mobilization: Patients undergo blood stem cell mobilization comprising filgrastim (G-CSF) subcutaneously once daily for 3 days (i.e., through the day before the last stem cell collection).
* Stem cell collection: Patients undergo collection of G-CSF-mobilized blood stem cells until the target number of stem cells (at least 2 x 10\^6 cluster of differentiation-34-positive cells) is reached.
* Conditioning regimen: Patients receive high-dose melphalan IV on days -3 to -2.
* Autologous stem cell transplantation: Patients undergo blood stem cell infusion on day 0.

After completion of study therapy, patients are followed at 3, 6, and 12 months and then annually thereafter.

HD Melphalan and SCT in Patients With IGDD or LCDD

High-Dose Melphalan and Autologous Stem Cell Transplantation (HDM/SCT) in Light-Chain Deposition Disease (LCDD) and Immunoglobulin Deposition Disease (IGDD)

Boston Medical Center

Principal Investigator

Mobilization with Filgrastim Stem Cell collection Melphalan Conditioning Stem Cell infusion

filgrastim: 16 mcg/kg daily beginning 3 days prior to SCC through day before final SCC

melphalan: 70-100 mg/m2/day will be administered intravenously on Days -3 and -2

Stem Cell Infusion: infusion of previously collected stem cells on Day 0

SCT With Melphalan Conditioning

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Dr. Vaishali Sanchorawala, Director of Stem Cell Transplant Program

No data were collected or analyzed due to study termination

Hematologic Response Rate

Predictability of Early Free Light-chain Response for Heme Response

Organ or Clinical Response

Overall Survival

Tolerability

Mobilization with Filgrastim Stem Cell collection (SCC) Melphalan Conditioning Stem Cell infusion

filgrastim: 16 mcg/kg daily beginning 3 days prior to SCC through day before final SCC

melphalan: 70-100 mg/m2/day will be administered intravenously on Days -3 and -2

Stem Cell Infusion: infusion of previously collected stem cells on Day 0

Overall Study

Nutritional and Metabolic Diseases

Symptoms and General Pathology

Monoclonal Gammopathy of Undetermined Significance

Amyloidosis

Immunoglobulin Light-chain Amyloidosis

Hypergammaglobulinemia

Proteostasis Deficiencies

Metabolic Diseases

AL Amyloidosis

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Antirheumatic Agents

Dexamethasone

Cyclophosphamide

Bortezomib

Daratumumab

Dexamethasone acetate

Daratumumab:

Cyclophosphamide Bortezomib Dexamethasone

Patient will receive Dara-CyBorD (Daratumumab, Bortezomib, Cyclophosphamide, Dexamethasone) for at least 6 cycles, and then Daratumumab maintainance.

Drug: Daratumumab: 16mg/kg IV dose OR 1800 mg subcutaneously Drug: Cyclophosphamide: 300 mg/m\^2 as an oral or IV dose Drug: Bortezomib: 1.3 mg/m\^2 as an subcutaneous (SC) injection. Drug: Dexamethasone: 20-40mg Patients will receive the above drugs (Dara-CyBorD) on Days 1, 8, 15, 22 in every 28-day cycle for a maximum of 6 cycles. Daratumumab will be administered weekly for the first 8 weeks (2 cycles), then every 2 weeks for 4 cycles (cycles 3-6), and then every 4 weeks until progression of disease or subsequent therapy for a maximum of 1 years.

Note: If patients achieve less than hematologic VGPR by cycle 3 or less than PR by cycle 2, treatment plan will be allowed to discontinued, according to treatment principle in systemic light chain amyloidosis.

Dara-CyBorD

Jin Lu

Yang Liu

Junling Zhuang

Junling Zhuang, MD

Jin Lu, MD

Juan Li

Juan Li, MD

This is an open-label, multicenter, Phase 2 study in subjects with newly diagnosed monoclonal immunoglobulin deposition disease treated with daratumumab, bortezomib, cyclophosphamide, and dexamethasone.

The current study aims to investigate daratumumab, bortezomib, cyclophosphamide, and dexamethasone regimen in patients with newly diagnosed monoclonal immunoglobulin deposition disease. Approximately 25 subjects will receive primary therapy with daratumumab-CyBorD. The primary endpoint is overall complete hematologic response (CHR) rate at 6 months.

Daratumumab, Bortezomib, Cyclophosphamide, and Dexamethasone Therapy for Patients With MIDD

Daratumumab, Bortezomib, Cyclophosphamide, and Dexamethasone Therapy for Patients With Monoclonal Immunoglobulin Deposition Disease

Hematologic complete response requires absence of monoclonal protein by immunofixation electrophoreses of both serum and urine as well as a normal FLC ratio (FLCr). CR is considered when FLCr was altered in favour of the non-amyloidogenic, uninvolved FLC (uFLC), even though the ratio may not have been normalised.

Cardiac response (for patients with cardiac involvement) at 6 months

Minimal residual disease status at 6 months

Treatment-related adverse events up to 2 years

Peking University People's Hospital

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
HD Melphalan and SCT in Patients With IGDD or LCDD	NCT00681044	Multiple Myelom...	filgrastim melphalan Stem Cell Infus...	18 Years - 120 Years	Boston Medical Center
HD Melphalan and SCT in Patients With IGDD or LCDD	NCT00681044	Multiple Myelom...	filgrastim melphalan Stem Cell Infus...	18 Years - 120 Years	Boston Medical Center
Daratumumab, Bortezomib, Cyclophosphamide, and Dexamethasone Therapy for Patients With MIDD	NCT06418477	Monoclonal Gamm...	Dara-CyBorD	18 Years -	Peking University People's Hospital

Spots Global Cancer Trial Database for monoclonal immunoglobulin deposition disease