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

Antineoplastic Agents

All Drugs and Chemicals

Melphalan

Lenograstim

Bortezomib

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

Adjuvants, Immunologic

Neupogen 16mcg/kg x 4 days Stem cell collection Drug: high dose melphalan 140 or 200 mg/m2 stem cell infusion

Neupogen 16mcg/kg x 4 days Stem Cell collection drug: high-dose melphalan 140 or 200 mg/m2 drug: Bortezomib 1.0 mg/m2/dose x 4 doses stem cell infusion

Conditioning Regimen:

Drug: Bortezomib: 1.0 mg/m2/dose D -6, D -3, D +1, D + 4 Drug: Melphalan: 70-100 mg/m2/dose D -2, D -1

Conditioning Regimen:

Drug: Melphalan: 70-100 mg/m2/dose D -2, D -1 Stem Cell Transplant: D 0

granulocyte colony-stimulating factor (G-CSF) mobilization 16mcg/kg x 4 days

Neupogen

collect at least 2.5 million cluster of differentiation 34 (CD34)+ stem cells

Stem Cell Collection

infusion of previously collected autologous stem cells

Stem cell infusion

Vaishali Sanchorawala, MD

Standard treatment for AL Amyloidosis is high-dose melphalan and stem cell transplant.

This study will compare the safety and effectiveness of standard treatment with high-dose melphalan and stem cell transplant, compared with investigational bortezomib when used in combination with standard treatment with high-dose melphalan and stem cell transplant for AL amyloidosis.

This study seeks to enroll patients with AL amyloidosis who have been recommended for standard treatment with high-dose melphalan and stem cell transplant.

Standard treatment for this disease is high-dose melphalan and stem cell transplant.

The purpose of this study is to compare the safety and effectiveness of standard treatment with high-dose melphalan and stem cell transplant, compared with investigational bortezomib when used in combination with standard treatment with high-dose melphalan and stem cell transplant for AL amyloidosis.

Patients enrolled in this study will receive either standard treatment with high-dose melphalan and stem cell transplant, or investigational bortezomib used in combination with standard treatment with high-dose melphalan and stem cell transplant.

Trial of High Dose Melphalan/Stem Cell Transplant With or Without Bortezomib

Phase III Trial of High-dose Melphalan and Stem Cell Transplantation Versus High-dose Melphalan and Bortezomib and Stem Cell Transplantation in Patients With AL Amyloidosis

Hematologic response defined as: at least 50% improvement in the difference between involved and uninvolved free light chains

Number of serious adverse events per participant based on Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

duration of overall survival measured in days

analysis of number of patients with organ response, as defined on page 13 of the detailed protocol for kidney, heart and liver.

Boston Medical Center

Principal Investigator

Adverse event data were collected from the time of study entry through the date of program discharge, once blood cell counts returned to normal.

Neupogen 16mcg/kg x 4 days Stem cell collection Drug: high dose melphalan 140 or 200 mg/m2 stem cell infusion

Melphalan: Conditioning Regimen:

Drug: Melphalan: 70-100 mg/m2/dose D -2, D -1 Stem Cell Transplant: D 0

Neupogen: granulocyte colony-stimulating factor (G-CSF) mobilization 16mcg/kg x 4 days

Stem Cell Collection: collect at least 2.5 million cluster of differentiation 34 (CD34)+ stem cells

Stem cell infusion: infusion of previously collected autologous stem cells

Neupogen 16mcg/kg x 4 days Stem Cell collection drug: high-dose melphalan 140 or 200 mg/m2 drug: Bortezomib 1.0 mg/m2/dose x 4 doses stem cell infusion

Bortezomib: Conditioning Regimen:

Drug: Bortezomib: 1.0 mg/m2/dose D -6, D -3, D +1, D + 4 Drug: Melphalan: 70-100 mg/m2/dose D -2, D -1

Melphalan: Conditioning Regimen:

Drug: Melphalan: 70-100 mg/m2/dose D -2, D -1 Stem Cell Transplant: D 0

Neupogen: granulocyte colony-stimulating factor (G-CSF) mobilization 16mcg/kg x 4 days

Stem Cell Collection: collect at least 2.5 million cluster of differentiation 34 (CD34)+ stem cells

Stem cell infusion: infusion of previously collected autologous stem cells

Melphalan + Bortezomib

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Early termination after enrollment held for toxicity evaluation; then closed due to competing trial.

Two participants were not evaluable as they expired and did not have a post-treatment response evaluation.

Number of Participants With Hematologic Response

Toxicities

The protocol was closed prior to the 5-year period of assessment, so 5-year survival assessment of only two participants was assessed.

Overall Survival

Due to early termination, organ response data was not collected.

Number of Participants With Organ Response

Overall Study

Lymphoma

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Lymphatic Diseases

Lymphoma, Non-Hodgkin

Lymphosarcoma

Peripheral T-cell Lymphoma

Antirheumatic Agents

Anti-Inflammatory Agents

Anti-Infective Agents

Gemcitabine

Etoposide

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Prednisone

Vincristine

Plerixafor

Etoposide phosphate

Busulfan

Antimetabolites

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Tubulin Modulators

Antimitotic Agents

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Patients received 6 cycles of induction chemotherapy: Cyclophosphamide, Doxorubicin, Vincristine, Etoposide and Prednisone (CHOEP) (5 if previously received 1 cycle of CHOP). CHOP was given at standard doses, with a dose of etoposide of 100 mg/m2 intravenously (IV) or 200 mg/m2 orally added on days 1-3 of each cycle. Patients who did not achieve a partial (PR) or complete (CR) remission at restaging after either 3 or 6 cycles were taken off study. Responders after 6 cycles had stem cell (SC) mobilization using filgrastim and plerixafor (if necessary) within 4 weeks of the end of induction. SC mobilization, harvesting, and reinfusion were performed per standard institutional protocol. A minimum collection of 2x106 CD34+ cells/kg was required to proceed to autologous stem cell transplant. Conditioning was comprised of gemcitabine 2700 mg/m2 on days -8 and -3, IV busulfan 105 mg/m2 days -8 to -5, and melphalan 60 mg/m2 given daily on days -3 and -2 (per MD Andersen protocol).

Filgrastim

Palifermin

Stem Cell Transplant

Philippe Armand, MD

The current standard of care for the frontline treatment of peripheral T-cell lymphomas (PTCL) is induction chemotherapy followed by autologous stem cell transplantation (ASCT). However, many patients are unable to get to ASCT or relapse after ASCT, with a poor prognosis. Recently, a novel ASCT conditioning regimen of gemcitabine, busulfan and melphalan (Gem/Bu/Mel) has been reported to lead to favorable outcomes in this disease. We therefore designed a frontline regimen of CHOEP induction followed by Gem/Bu/Mel ASCT, and report the results of a phase 2 study of this regimen in patients with PTCL.

Objectives:

Primary

* To estimate the proportion of patients alive and progression-free at 24 months after beginning induction therapy

Secondary

* To estimate the response rate (complete remission (CR) and partial remission (PR)) after CHOEP x 6 and after Gem/Bu/Mel ASCT
* To estimate overall survival (OS), progression-free survival (PFS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM)
* To estimate the toxicity (grade 3 and above)
* To estimate the rate of successful stem cell mobilization after CHOEP in responding patients
* To estimate the proportion of patients who can successfully complete the entire treatment regimen
* To estimate the time to engraftment of neutrophil and platelet engraftment after ASCT
* To determine whether tumor DNA can be detected in peripheral blood of patients before therapy
* To evaluate the changes and prognostic relevance in detectable tumor DNA in peripheral blood after induction chemotherapy (CHOEP) and after Gem/Bu/Mel ASCT

CHOEP + High Dose Therapy + Auto SCT for T-Cell Lymphoma

A Phase II Study of CHOEP Induction Followed by Gemcitabine/Busulfan/Melphalan Autologous Stem Cell Transplantation for Patients With Newly Diagnosed T-Cell Lymphoma

24-month progression-free survival rate is defined as the proportion of patients remaining alive and progression-free at 24 months from start of induction therapy. Disease progression was assessed using a combination of CT scans and PET scans. Progression was categorized according to standard lymphoma response criteria, specifically the Revised Response Criteria (Cheson 2007).

Induction response is the defined as the proportion of patients who achieve complete remission (CR) or partial remission (PR) during 6 cycles of induction therapy. Response was assessed was using a combination of CT scans and PET scans. Partial and complete response were categorized according to standard lymphoma response criteria, specifically the Revised Response Criteria (Cheson 2007). Given the cycle length of 3 weeks, induction duration per protocol was 18 weeks.

Massachusetts General Hospital

Beth Israel Deaconess Medical Center

Dana-Farber Cancer Institute

Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. Other AEs were defined as events with treatment attribution of possible, probable or definite and grades 1 or 2 per CTCAEv4. No further data is available to specify classification of other beyond the general term.

CHOEP + High Dose Therapy + Auto SCT

Age, Continuous

United States

Region of Enrollment

Stage I

Stage II

Stage III

Stage IV

Stage

The analysis dataset is comprised of all enrolled patients.

The trial closed early due to poor accrual. The small sample size precludes definitive conclusions.

Philippe Armand MD, PhD

The analysis dataset is comprised all enrolled patients.

24-month Progression-Free Survival Rate

Induction Response

Ifosfamide

Ofatumumab

Isophosphamide mustard

Mesna

Ofatumumab 1000 mg by vein on Day 1 and 2000 mg by vein on Day 8. Ifosfamide 3.33 gm/m2 by vein on Days 2, 3, and 4 continuously. Etoposide 150 mg/m2 by vein over 2 hours every 12 hours for 6 doses. Mesna 2 gm/m2 by vein over 1 hour on Day 2 (given before Ifosfamide starts). Mesna 2.66 gm/m2/day by vein continuous infusion given over 24 hours daily for 3 days starting on Day 2 (together with Ifosfamide). After Ifosfamide/Mesna, 2 gm/m2 by vein given over 12 hours for one dose. G-CSF 6 mcg/kg subcutaneously twice a day on day 6 (rounded off to the nearest vial) until completion of apheresis. Blood stem cells will be collected when blood counts have returned to normal (about 10-16 days after chemotherapy). Stem cell collection takes about 4 hours each time.

1000 mg by vein on Day 1 and 2000 mg by vein on Day 8

3.33 gm/m2 by vein on Days 2, 3, and 4 continuously.

150 mg/m2 by vein over 2 hours every 12 hours Days 2, 3, and 4 for 6 doses.

2 gm/m2 by vein over 1 hour on Day 2 (given before Ifosfamide starts)

2.66 gm/m2/day by vein continuous infusion given over 24 hours daily for 3 days starting on Day 2 (together with Ifosfamide)

After Ifosfamide/Mesna, 2 gm/m2 by vein given over 12 hours for one dose.

6 mcg/kg subcutaneously twice a day on day 6 (rounded off to the nearest vial) until completion of apheresis.

G-CSF

Blood stem cells will be collected when blood counts have returned to normal (about 10-16 days after chemotherapy). Stem cell collection takes about 4 hours each time.

Issa F. Khouri, MD,BS

The goal of this clinical research study is to learn if it is possible to collect stem cells after ofatumumab and chemotherapy treatment. This study will also evaluate side-effects, number of stem cells collected, and the number of procedures that are needed to collect enough stem cells.

The Study Drugs:

Ofatumumab is a human monoclonal antibody for the CD20 protein designed to bind to the surface of some of the white blood cells (B-cells). It can destroy cancer cells that come from B-cells, and can be used to treat cancers of B-cells such as resistant CLL (chronic lymphocytic leukemia).

Etoposide is designed to slow or stop the growth of cancer cells.

Filgrastim promotes the growth of white blood cells, which help to fight infections.

Ifosfamide is designed to slow or stop the growth of cancer cells.

Mesna is a drug that protects bladder cells from damage by the chemotherapy drug ifosfamide. It is used to decrease the risk of bleeding in the bladder.

Treatment Administration:

You will be admitted to the hospital. You will have to stay in the hospital for 4-6 days for this part of the treatment.

On Day 1, you will receive ofatumumab through the CVL over 6-8 hours.

On Days 2, 3, and 4, you will receive ifosfamide and mesna continuously and etoposide every 12 hours. Mesna is given to help decrease the risk of developing side effects.

As an outpatient, you will receive a higher dose of ofatumumab (about 1 week after the first one) through the CVL over 10-12 hours.

Beginning on Day 6, you will get G-CSF (filgrastim) injections (given under the skin) and will continue to be given until enough stem cells have been collected.

Tests and Procedures:

Every day while you are in the hospital, you will have a physical exam and you will be asked about any side effects you may be having. After you are no longer in the hospital, you will have a physical exam and you will be asked about any side effects you may be having when the doctor thinks it is needed.

While you are waiting for enough stem cells to be collected, you will have blood drawn (about 1 tablespoon) for routine tests at least 3 times a week. If your doctor thinks it is needed, you may have blood drawn more often.

Stem Cell Collection:

Blood stem cells will be collected when your blood counts have returned to normal (about 10-16 days after chemotherapy). The process of stem cell collection takes about 4 hours each time. You will have stem cells collected each day until enough are collected (between 1-6 sessions). A machine is attached to the CVL and blood is withdrawn. The blood then flows through the machine, which removes stem cells from the blood. The blood is then returned back to you through the CVL. The stem cells are then frozen and stored. These stem cells will be given back to you after the next phase of treatment to help your blood counts recover after high dose chemotherapy. After enough stem cells have been collected, you will be admitted to the hospital for high dose chemotherapy. You will sign a separate consent before you receive high dose chemotherapy.

During the stem cell collection, blood (about 2 teaspoons) will be drawn through the CVL to check for cell markers that can affect the response of the cell counts and to check the status of the disease.

Length of Study:

Patients will be followed for up to 12 months after the transplant. You will be taken off study early if the stem cell collection does not work.

This is an investigational study. Etoposide and ifosfamide are FDA approved and are commercially available for lymphomas. Ofatumumab has been approved by the FDA for treatment of recurrent refractory chronic lymphocytic leukemias. G-CSF and Mesna are FDA approved and commercially available. The use of Ofatumumab for the collection of stem cells is investigational.

Up to 50 patients will take part in this study. All will be enrolled at MD Anderson.

Chemotherapy Plus Ofatumumab Followed by G-CSF for Mobilization of Peripheral Blood Stem Cells in Patients With Non-Hodgkin's Lymphomas

Feasibility of mobilization with ofatumumab + chemotherapy is defined as successful collection of 2 x 10\^6CD34+ stem cell/kg and successful purging of the apheresis product of all the markers (i.e., monoclonal B-cells, bcl-2, bcl-1 and/or JH) that were found to be positive on pretreatment evaluation. Mobilization rate is number of participants with successful collection out of total study participants.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trial of High Dose Melphalan/Stem Cell Transplant With or Without Bortezomib	NCT02489500	AL Amyloidosis	Bortezomib Melphalan Neupogen Stem Cell Colle... Stem cell infus...	18 Years -	Boston Medical Center
CHOEP + High Dose Therapy + Auto SCT for T-Cell Lymphoma	NCT01746173	T-cell Non-Hodg...	Cyclophosphamid... Doxorubicin Vincristine Etoposide Prednisone Filgrastim Plerixafor Stem Cell Colle... Palifermin Gemcitabine Busulfan Melphalan Stem Cell Trans...	18 Years - 70 Years	Dana-Farber Cancer Institute
CHOEP + High Dose Therapy + Auto SCT for T-Cell Lymphoma	NCT01746173	T-cell Non-Hodg...	Cyclophosphamid... Doxorubicin Vincristine Etoposide Prednisone Filgrastim Plerixafor Stem Cell Colle... Palifermin Gemcitabine Busulfan Melphalan Stem Cell Trans...	18 Years - 70 Years	Dana-Farber Cancer Institute
Chemotherapy Plus Ofatumumab Followed by G-CSF for Mobilization of Peripheral Blood Stem Cells in Patients With Non-Hodgkin's Lymphomas	NCT01329900	Lymphoma	Ofatumumab Ifosfamide Etoposide Mesna G-CSF Stem Cell Colle...	18 Years - 70 Years	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for stem cell collection