Nutritional and Metabolic Diseases

All Conditions

Neoplasms

Immune System Diseases

Blood and Lymph Conditions

Rare Diseases

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

Dexamethasone

Melphalan

Lenalidomide

Dexamethasone acetate

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Up to 6 cycles of oral L-Mel-Dex, every 28 days Revlimid® 10 mg daily for 21 days, (add on therapy), Melphalan 0.15 mg/kg/day day 1-4, Dexamethasone 20 mg day 1-4

Stefan Schoenland, MD

The treatment with oral melphalan and prednisone has been recommended as standard treatment of AL amyloidosis but the results are rather disappointing. Another therapeutic option is pulsed high-dose dexamethasone + melphalan (Mel-Dex) with more encouraging results regarding the achievement of a faster disease response and higher rates of haematological remission. In the last 5 - 10 years, promising treatment outcomes after therapy with high-dose melphalan and autologous stem cell support have been reported by several groups but only highly selected patients are eligible for this treatment. Lenalidomide has been shown to be effective in phase II and III trials in MM patients. Because of the relationship to MM, Lenalidomide is a promising therapeutic option also for patients with AL amyloidosis. The addition of Lenalidomide to Mel-Dex could improve rate of complete response (CR) and organ response in patients not eligible for or refused high-dose chemotherapy.

A Trial of Treatment With Lenalidomide-Melphalan-Dexamethasone in Patients With Primary (AL) Amyloidosis

A Prospective Single Center Trial of Treatment With Lenalidomide-Melphalan-Dexamethasone in Patients With AL Amyloidosis

Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbH

Heidelberg University

Heart and Blood Diseases

Multiple Myeloma

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lenograstim

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Adjuvants, Immunologic

Melphalan + Stem Cell Infusion (Standard Dose): Standard Dose (Arm 1) = Stem cell dose of between 4-6 x 10\^6 cluster of differentiation 34 (CD34)/kg on Day 0. Melphalan 100 mg/m\^2 via a Central Venous Catheter (CVC) Over 15-20 Minutes on Days -3 and -2 prior to stem cell infusion. Granulocyte-colony stimulating factor (G-CSF) 5 mcg/kg given subcutaneously (under the skin) on a daily basis for approximately 10 days. Beginning Visit 1, twice a week, paper and automated phone interview of symptoms and quality of life questionnaires.

Melphalan + Stem Cell Infusion (High Dose): High Dose (Arm 2) = Stem cell dose of between 10-15 x 10\^6 CD34/kg On Day 0. Melphalan 100 mg/m\^2 via a Central Venous Catheter (CVC) Over 15-20 Minutes on Days -3 and -2 prior to stem cell infusion. Granulocyte-colony stimulating factor (G-CSF) 5 mcg/kg given subcutaneously (under the skin) on a daily basis for approximately 10 days. Beginning Visit 1, twice a week, paper and automated phone interview of symptoms and quality of life questionnaires.

100 mg/m\^2 via a Central Venous Catheter (CVC) Over 15-20 Minutes on Days -3 and -2 prior to stem cell infusion.

Stem Cell Infusion is Day 0.

Standard Dose (Arm 1) = Stem cell dose of between 4-6 x 10\^6 CD34/kg On Day 0

High Dose (Arm 2) = Stem cell dose of between 10-15 x 10\^6 CD34/kg On Day 0.

Stem Cell Infusion

Beginning Visit 1, twice a week, paper and automated phone interview of symptoms and quality of life questionnaires.

Questionnaires

5 mcg/kg given subcutaneously (under the skin) on a daily basis for approximately 10 days.

Granulocyte-colony stimulating factor (G-CSF)

Collection of stem cells from blood collected either through CVC or from a vein in one arm.

Apheresis

Nina Shah, MD

The goal of this clinical research study is to learn whether higher doses of stem cells can help to decrease the symptoms that occur after melphalan. Another goal of the study is to see how the dose of infused stem cells affects the levels of certain proteins in your blood. Researchers also want to learn how the dose of stem cells that you receive affects the quality of your life during the weeks after the transplant procedure.

Stem cells are found in the bone marrow and bloodstream, and they rebuild blood, bone marrow, and the immune system. This study uses autologous stem cells, which are stem cells collected from your own blood. Melphalan is designed to damage the DNA (the genetic material) of cells, which may cause cancer cells to die. Granulocyte-colony stimulating factor (G-CSF) is designed to help the bone marrow to make more white blood cells. G-CSF is used in this study to help move your stem cells out of the bone marrow and into the bloodstream. If your doctor decides it is needed, you will also receive chemotherapy to help your blood stem cells move out of your bone marrow and into your blood. This allows the stems cells to be collected. Researchers also want to learn how the dose of infused stem cells affects the levels of certain cytokines in your blood. Cytokines are proteins that can cause symptoms such as fatigue and fever.

Treatment Plan:

If you are found to be eligible to take part in this study, you will need to have a central venous catheter (CVC) placed. A CVC is a flexible sterile tube that will be placed into a large vein that runs under your collarbone. Having the CVC allows blood to be drawn and medications to be given more easily and with less discomfort. You will be asked to sign a separate consent form to have the CVC placed, and the procedure will be more fully explained to you at that time.

If your doctor decides it is needed, you will receive chemotherapy to help your blood stem cells move out of your bone marrow and into your blood. You will be asked to sign a separate consent form for this chemotherapy.

Starting on the day of the stem cell infusion, you will receive G-CSF by injection under your skin. You will have the G-CSF injected once or twice a day for about 10 days. The injections may be given at home, if possible. You will be taught how to inject the G-CSF, or someone who agrees to be responsible for giving you the injections may also be taught.

Once the number of stem cells in your bloodstream is high enough, the stem cells will be collected over the course of 2-5 days. You will be asked to sign a separate consent form for the stem cell collection, and the process will be described in more detail at that time. Not counting the blood that is returned to you, about 32 tablespoons of blood will be drawn for the stem cell collection.

You will keep receiving the daily G-CSF injections on the days that your stem cells are collected. A procedure called apheresis will be used to collect the stem cells. During the apheresis, blood will be collected either through your CVC or from a vein in one arm. The blood will be processed through a machine to remove the stem cells, and then the rest of the blood will be returned to you through your CVC or through a vein in the other arm. The apheresis procedure will last several hours each time. You will be asked to sign a separate consent form for the apheresis procedure. You will have enough stem cells collected so that you will be able to have either 1 transplant with high doses of stem cells or 2 transplants with standard doses of stem cells. Your stem cells will be frozen (cryopreserved) until being given back to you.

About 2 weeks after your stem cells have been collected, you will have chemotherapy with melphalan. The melphalan will be given over 30 minutes through your CVC. Since this treatment destroys the normal bone marrow in addition to the myeloma cells, your blood stem cells must be given back to you. This is because blood stem cells are able to refill the bone marrow. If your doctor thinks it is needed, you may be admitted to the hospital the day before you receive melphalan to receive fluids by vein to hydrate you.

Two (2) days after receiving the melphalan, your previously collected stem cells will be unfrozen and given back to you through your CVC, similar to a blood transfusion. This is called an autologous stem cell transplant. You will be randomly assigned (as in the toss of a coin) to receive either a standard amount of stem cells or an experimental amount of stem cells. You have a 50/50 chance of being assigned to either group. After you receive your stem cells, you will be given G-CSF as an injection under the skin. You will keep having G-CSF injections until your white blood cell count returns to normal.

After your stem cells have been given back to you, it will take about 2 weeks for enough blood cells to be made. During this time, it is possible that you might not be making any blood cells. If this happens, you may need to have several red blood cell and platelet transfusions. You will receive antibiotics if infections occur, and you may need to be given feedings through the CVC.

The entire stem cell transplantation process will be done on an outpatient basis, if possible. Otherwise, you may need to stay in the hospital for up to 3-4 weeks.

After the stem cell transplant is completed, you will need to return to the clinic for follow-up visits at least once a week for a month, or more often if the doctor feels it is necessary. The follow-up visits will include the same tests and procedures as is standard of care. Research blood (about 2-4 teaspoons each time) will also be drawn on Day -2, Day 0, Day +3, Day +5, and Day +7; twice a week during weeks 2 and 3; and then once during week 4 for immune system tests.

Questionnaires and Physical Tests:

At several times during the study, you will be asked to complete a questionnaire about your symptoms and quality of life. Sometimes the questionnaire will be done over the phone with an automated phone system. Rating your symptoms using the telephone system should take less than 5 minutes for each call. The rest of the time questionnaires will be performed on paper and through phone interviews. You will also be asked to perform physical tests, including walking for 6 minutes and getting in and out of a chair.

The research nurse will teach you how to use the telephone system for measuring symptoms and your quality of life. You will perform the physical function tests and complete the symptom questionnaire. You will also have tests of the sensitivity of the nerves in your arms and legs. Blood (about 4-5 tablespoons) will be drawn for routine tests. Completing the questionnaires and tasks at this first visit should take about an hour.

During your hospital stay or clinic visits for the stem cell transplant, you will be asked on Day -2 (2 days before the transplant), Day 0, Day +3, Day +5, and Day +7 after the transplant to fill out a paper questionnaire that measures symptoms. You will also be asked on the same days to complete brief tasks that measure physical function.

During Weeks 2 and 3 you will be asked to fill out the paper questionnaire twice a week and complete the tasks of physical function once a week. During Week 4, you will be asked to fill out the questionnaire once and complete the tasks of physical function once. During Week 4, the sensory testing of the nerves in your arms and legs will also be repeated. On the same day as the physical tests, the research nurse will ask you to practice using the telephone system for measuring symptoms.

After you leave the hospital or clinic, the telephone system will call you at home. The calls will occur 1 time a week from Week 5 through Week 12 after the transplant, then 1 time a month during Months 3, 6, and 12 (+/- 1 month). The telephone system will ask you to rate how strong and tolerable the symptoms are, and how much the symptoms interfere with your daily life.

During the clinic visit that occurs about 90 days after the transplant, you will be asked to complete brief tasks that measure physical function, and you will also have the last test of the nerves in your arms and legs.

You will be on study for about 1 year.

This is an investigational study. Melphalan with autologous stem cell transplantation is FDA-approved for the treatment of myeloma and amyloidosis. The medications and treatment for this study are all commercially available. Up to 100 patients will take part in this study. All will be enrolled at MD Anderson.

Trial of Two Stem Cell Doses To Reduce Transplant Induced Symptom Burden

Randomized Phase II Trial of Two Stem Cell Doses To Reduce Transplant Induced Symptom Burden in High Risk Patients With Multiple Myeloma or Amyloidosis

MD Anderson Symptom Inventory (MDASI) Scale regularly administered during the first year following transplantation. This instrument is brief, easily understood, and provides a measure of the intensities of cancer-related symptoms. Participants rate the intensity of physical, affective, and cognitive symptoms on 0 to 10 numeric scales from "not present" (score of 0) to "as bad as you can imagine" (score of 10). Participants also rate amount of interference with daily activities caused by symptoms on 0 to 10 numeric scales from "did not interfere" (Score of 0) to interfered completely (score of 10).

MD Anderson Symptom Inventory (MDASI) Scale regularly administered during the first year following transplantation. This instrument is brief, easily understood, and provides a measure of the intensities of cancer-related symptoms. Participants rate the intensity of physical, affective, and cognitive on 0 to 10 numeric scales from "not present" (score of 0) to "as bad as you can imagine" (score of 10). Participants also rate amount of interference with daily activities caused by symptoms on 0 to 10 numeric scales from "did not interfere" (Score of 0) to interfered completely (score of 10)

M.D. Anderson Cancer Center

Patients undergoing ASCT for MM who were ≥60 years old or had AL amyloidosis were randomized to receive either a standard (4-6×106 cells/kg) of CD34+ cells after melphalan 200 mg/m2.

Standard Dose Stem Cell Group

Patients undergoing ASCT for MM who were ≥60 years old or had AL amyloidosis were randomized to receive high dose (10-15×106 cells/kg) of CD34+ cells after melphalan 200 mg/m2.

High Dose Stem Cell Group

Total

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Dr. Richard E Champlin,MD/Chair, Stem Cell Transplantation

Intention to treat analysis, all treated participants. One participant in High Dose group did not complete adequate number of MDASI's for analysis.

Mean Symptom Severity Burden as Measured by MDASI Scores

Intention to treat analysis, all treated participants. One participant in High Dose group did not complete adequate number of MDSAIs for analysis.

Overall Study

Symptoms and General Pathology

Neoplasm, Residual

Neoplastic Processes

Raymond Comenzo, MD

This protocol will assess patients with AL amyloidosis who achieve a complete response (CR) or very good partial response (VGPR) to therapy for minimal residual disease (MRD). Three approaches to MRD testing will be used since there is no established method. The investigators will clone and sequence each patient's light chain (LC) gene and design patient-specific primers to evaluate genomic DNA from future marrow specimens. Whole genome sequencing (WGS) will be used to test baseline and follow-up marrow cell DNA, seeking copy number variations in chromosomes 1 and 2 or 22, and structural variations in chromosomes 11 and 14, consistent with the known genetic abnormalities in AL and with clonal LC gene use. Plasma protein analysis by mass spectrometry will also be used to look for fragmentary protein sequences associated with the culprit LC gene of each subject. The feasibility and predictive value of these three approaches in patients achieving CR or VGPR will be evaluated. This protocol will help provide insight into the ways that the disease changes and progresses. MRD testing is likely an important next step in AL management.

This protocol will assess AL amyloidosis patients who achieve a CR or VGPR to first-line therapy for evidence of MRD by Q-PCR, NGS, and plasma protein analysis by mass spectrometry using marrow cells obtained annually at times of standard clinical evaluations.

A bone marrow aspirate sample from diagnosis will be used to create a baseline profile of each patient's disease. This sample will allow the investigators to create the primer-probe sets required for MRD testing by Q-PCR, which will be conducted after the patient has achieved a CR or VGPR. A baseline bone marrow biopsy sample will either be taken at the time of consent or can be taken from storage if the patient has previously consented to have their marrow cells banked for research purposes. An extra 15 mL of aspirate will be taken from their diagnostic bone marrow biopsy, which is routinely conducted on newly diagnosed patients for clinical purposes. Annual bone marrow aspirates will not be taken for research purposes until after the patient has responded. Patients will remain on protocol, but only begin MRD testing after achieving a CR or VGPR to first-line therapy at which point annual marrow collections for MRD testing will begin. In the event the patient does not reach a CR or VGPR to first-line therapy, the baseline bone marrow aspirate from diagnosis will be discarded.

Patients who choose to allow their marrow to be used in this study will sign a consent form specifically for this study. At the time of consent, three green top tubes of peripheral blood will be obtained for WGS of non-tumor cells. No further blood samples will be required for this study. After achieving a CR or VGPR, patients will be completely re-staged as is standard of care at annual intervals. Samples to test for the presence of MRD in their marrows will be obtained at these times of clinical re-staging for up to 3 years after their response to therapy. Both blood and bone marrow samples for this study will be immediately taken to an on-site laboratory where they will be briefly stored before testing. This will ensure no study samples interfere with routine clinical care.

In order to test for the presence of MRD, three techniques will be used: Q-PCR, WGS, and plasma protein analysis by mass spectrometry. Both Q-PCR and WGS will use genomic DNA from marrow aspirate samples. To make primer-probe sets for Q-PCR, bone marrow samples from baseline will be used to create individualized primer-probe sets that can recognize the genetically unique LC gene that causes each patient's disease. To perform WGS, genomic DNA will be supplied to the core genetics laboratory for creation of a library and multiplex next generation sequencing. To perform plasma protein analysis, plasma will be isolated from a portion of each subject's peripheral blood and bone marrow aspirate samples in an on-site laboratory. Each subject's de-identified LC gene sequence and their de-identified plasma samples will then be sent to Memorial Sloan-Kettering Cancer Center (MSKCC) for mass spectrometry to look for fragmentary protein sequences associated with the culprit LC gene of each subject.

After reaching a CR or VGPR, at annual evaluations for up to 3 years, the genomic DNA from the research sample of bone marrow collected during standard of care clinical procedures will be used to confirm maintenance of response by testing for the presence of MRD with each of the 3 methods (Q-PCR, WGS, and plasma protein analysis) noted above. Marrow material collected for the purposes of this study will not be stored after analysis, and primer-probe set design will be conducted entirely within Tufts Medical Center. Any marrow samples not fully consumed during analysis will be destroyed.

By using these three methods this protocol will determine whether one method is superior to the others and whether the three methods produce results that correlate with each other. The decision to discontinue participation in MRD testing will be made by the patient and the physician on an individual basis. Patients who have relapse or hematologic progression of disease during the three year period by standard blood and urine tests will no longer have testing for MRD.

Minimal Residual Disease as a Possible Predictive Factor for Relapse in Patients With AL Amyloidosis

After achievement of a CR or VGPR, minimal residual disease testing (using Q-PCR, WGS, and plasma protein analysis by mass spectrometry) will be done annually for up to 3 years. These tests will show either the presence of absence of minimal residual disease. These findings will then be correlated with progression free survival as assessed through standard clinical tests for AL amyloidosis.

Tufts Medical Center

Antibodies

Antibodies, Monoclonal

Immunoglobulins

NEOD001 will be administered intravenously once every 28 days. The starting dose will be 0.5 mg/kg. Dose escalation will continue until the the maximum tolerated dose is determined for single agent NEOD001. Approximately 20 additional subjects will be treated with the maximum tolerated dose.

Monoclonal antibody administered by intravenous infusion every 28 days.

NEOD001

Julia Martinisi

Dose escalation study to determine the maximum tolerated dose of NEOD001 in approximately 30 subjects with AL amyloidosis. Expansion phase to evaluate safety, efficacy and pharmacokinetics of NEOD001 in 25 additional subjects at the maximum tolerated dose.

The purpose of the dose escalation phase of the study is to determine the maximum tolerated dose/Phase 2 recommended dose of NEOD001 when given as a single agent intravenously in approximately 30 subjects with AL amyloidosis.

The purpose of the expansion phase of the study is to evaluate the safety, preliminary efficacy and pharmacokinetics of single agent NEOD001 at the maximum tolerated dose/Phase 2 recommended dose in approximately 25 additional evaluable subjects.

Phase 1/2, Open Label, Dose Escalation Study of NEOD001 in Subjects With Light Chain (AL) Amyloidosis

A Phase 1/2, Open Label, Dose Escalation Study of Intravenous Administration of Single Agent NEOD001 in Subjects With Light Chain (AL) Amyloidosis

* Organ response
* Changes in organ function markers

* Adverse event profile
* Dose limiting toxicity and maximum tolerated dose

* Adverse event profile
* Dose Limiting Toxicity and maximum tolerated dose

• Pharmacokinetic parameters including Cmax, Tmax, AUC, Cav, Cmin, t½, CL, and Vz

• Measurement of anti-NEOD001 antibodies

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Trial of Treatment With Lenalidomide-Melphalan-Dexamethasone in Patients With Primary (AL) Amyloidosis	NCT00883623	Primary Amyloid...	Lenalidomide	18 Years - 74 Years	Heidelberg University
Trial of Two Stem Cell Doses To Reduce Transplant Induced Symptom Burden	NCT00651937	Multiple Myelom... Primary Amyloid...	Melphalan Stem Cell Infus... Questionnaires Granulocyte-col... Apheresis	60 Years -	M.D. Anderson Cancer Center
Minimal Residual Disease as a Possible Predictive Factor for Relapse in Patients With AL Amyloidosis	NCT02555969	Amyloidosis Primary Amyloid...		-	Tufts Medical Center
Minimal Residual Disease as a Possible Predictive Factor for Relapse in Patients With AL Amyloidosis	NCT02555969	Amyloidosis Primary Amyloid...		-	Tufts Medical Center
Phase 1/2, Open Label, Dose Escalation Study of NEOD001 in Subjects With Light Chain (AL) Amyloidosis	NCT01707264	Primary Amyloid...	NEOD001	18 Years -	Prothena Biosciences Ltd.

Spots Global Cancer Trial Database for primary amyloidosis