Reduced-Intensity Conditioning Followed By Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Multiple Myeloma

Reduced-Intensity Allogeneic HSC Transplantation From HLA-Matched Related and Unrelated Donors for Patients With Multiple Myeloma - A Multi-Center Trial

Sponsoren

Hauptsponsor: Fred Hutchinson Cancer Research Center

Mitarbeiter: National Cancer Institute (NCI)

Quelle Fred Hutchinson Cancer Research Center
Kurze Zusammenfassung

This phase I/II trial studies the side effects of giving reduced-intensity conditioning followed by donor peripheral blood stem cell transplant (PBSCT) and how well it works in treating patients with multiple myeloma (MM). Giving low doses of chemotherapy, such as fludarabine phosphate and melphalan, and total-body irradiation (TBI) before a donor PBSCT helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving mycophenolate mofetil and cyclosporine after transplant may stop this from happening.

detaillierte Beschreibung

PRIMARY OBJECTIVES:

I. To evaluate the efficacy of this approach by determining the 1-year progression-free survival (PFS) and overall survival (OS).

II. To evaluate day 100 non-relapse mortality.

III. To determine the incidences of grades II-IV acute graft-versus-host disease (GVHD) and chronic extensive GVHD.

OUTLINE:

PREPARATIVE REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -5 to -3 and intermediate-dose melphalan IV over 15-20 minutes on day -2. Patients also undergo low-dose TBI on day 0.

TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) on days -3 to 80 with taper to day 180 (related donors) or on days -3 to 100 with taper to day 180 (unrelated donors). Patients also receive mycophenolate mofetil PO BID on days 0-27 (related donors) or thrice daily (TID) on days 0-40 with taper to day 96 (unrelated donors).

After completion of study treatment, patients are followed up at 3, 6, 12, 18, and 24 months, and then annually thereafter for 5 years.

Gesamtstatus Completed
Anfangsdatum October 2002
Fertigstellungstermin October 14, 2012
Primäres Abschlussdatum October 2009
Phase Phase 1/Phase 2
Studientyp Interventional
Primärer Ausgang
Messen Zeitfenster
PFS At 1 year post-transplant
Non-relapse Mortality At day 100
Incidence of Acute GVHD (Grades III-IV) Up to 5 years
Incidence of Chronic (Extensive) GVHD Up to 5 years
Sekundäres Ergebnis
Messen Zeitfenster
OS At 6 months and then every year thereafter, up to 5 years
Engraftment Up to 5 years
Relapse Rate Up to 5 years
Response Rate Up to 5 years
Einschreibung 16
Bedingung
Intervention

Interventionsart: Drug

Interventionsname: fludarabine phosphate

Beschreibung: Given IV

Interventionsart: Drug

Interventionsname: melphalan

Beschreibung: Given IV

Interventionsart: Radiation

Interventionsname: total-body irradiation

Beschreibung: Undergo TBI

Anderer Name: TBI

Interventionsart: Drug

Interventionsname: mycophenolate mofetil

Beschreibung: Given PO

Interventionsart: Drug

Interventionsname: cyclosporine

Beschreibung: Given PO

Interventionsart: Procedure

Interventionsname: nonmyeloablative allogeneic hematopoietic stem cell transplantation

Beschreibung: Undergo reduced-intensity allogeneic PBSCT

Interventionsart: Procedure

Interventionsname: peripheral blood stem cell transplantation

Beschreibung: Undergo reduced-intensity allogeneic PBSCT

Interventionsart: Other

Interventionsname: laboratory biomarker analysis

Beschreibung: Correlative studies

Teilnahmeberechtigung

Kriterien:

Inclusion Criteria:

- Meet Salmon and Durie criteria for initial diagnosis of MM; transplant will be offered to patients with previously treated MM who meet one of the following criteria:

- Patient received at least one prior autologous or syngeneic hematopoietic SCT (HSCT) and now has progressive disease (PD) (greater than 25% increase in serum or urine paraprotein levels compared to best response status after autograft or appearance of new lytic bone lesions or plasmocytomas)

- Patient is not able to collect autologous PBSC due to poor marrow reserve (insufficient HSC-mobilization: < 2.5 x 10^6 cluster of differentiation [CD]34+ cells/kg); or contraindications to undergoing HSC-mobilization; patient now has PD and has received at least 4 cycles of standard chemotherapy (e.g. vincristine sulfate, doxorubicin hydrochloride, and dexamethasone [VAD]) in the past

- Patients must have the capacity to give informed consent

- DONOR: Human leukocyte antigen (HLA) genotypically identical sibling or phenotypically matched relative

- DONOR: HLA phenotypically matched unrelated donor (according to Standard Practice HLA matching criteria)

- Matched for serologically recognized HLA-A or B or C antigens and at least five of six HLA-A or B or C alleles

- Matched for HLA DRB1 and DQB1 alleles (defined by high-resolution typing) at the allele level

- DONOR: Donor must consent to filgrastim (G-CSF) administration and leukapheresis for PBSC collection

- DONOR: Donor must have adequate veins for leukapheresis or agree to placement of a temporary central venous catheter

Exclusion Criteria:

- Karnofsky score < 60%

- Left ventricular ejection fraction < 40% or symptomatic heart failure; ejection fraction is required if age > 50 years or there is a history of anthracycline exposure or history of cardiac disease

- Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bridging fibrosis, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL,or symptomatic biliary disease

- Diffusion capacity of carbon monoxide (DLCO) < 50% (corrected) or receiving continuous supplemental oxygen

- Creatinine clearance < 40 mL/min

- Patients with poorly controlled hypertension

- Seropositive for the human immunodeficiency virus (HIV)

- Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a > 20% risk of disease recurrence

- Pregnancy or breastfeeding

- Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment

- Not fully recovered from previous high-dose therapy:

- Persistent mucositis and gastrointestinal symptoms requiring hyperalimentation and/or intravenous hydration

- On steroids for autologous/syngeneic GVHD

- On IV antibiotics for documented infections

- Cytomegalovirus (CMV)-antigenemia positive

- On ganciclovir or foscarnet for previous CMV reactivation/infection; off of this therapy for less than two weeks despite documented CMV-antigenemia- negativity (identification [ID] should be consulted if there is persistent CMV antigenemia post autograft)

- Ongoing radiotherapy

- Patients who meet any of these criteria may be discussed with the principal investigator for recommendations as to the timing of the allograft

- Patients with active bacterial or fungal infections unresponsive to medical therapy

- DONOR: Identical twin

- DONOR: Donors unwilling to donate PBSC

- DONOR: Pregnancy

- DONOR: Infection with HIV

- DONOR: Inability to achieve adequate venous access

- DONOR: Known allergy to G-CSF

- DONOR: Current serious systemic illness

- DONOR: Failure to meet Fred Hutchinson Cancer Research Center (FHCRC) criteria for stem cell donation

- DONOR: Age < 12 years

- DONOR: A positive anti-donor cytotoxic crossmatch is an absolute donor exclusion

Geschlecht: All

Mindestalter: 18 Years

Maximales Alter: 70 Years

Gesunde Freiwillige: No

Insgesamt offiziell
Nachname Rolle Zugehörigkeit
Marco Mielcarek Principal Investigator Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Ort
Einrichtung:
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle, Washington, 98109, United States
University of Torino | Torino, 10126, Italy
Standort Länder

Italy

United States

Überprüfungsdatum

September 2017

Verantwortliche Partei

Art: Principal Investigator

Ermittlerzugehörigkeit: Fred Hutchinson Cancer Research Center

Vollständiger Name des Ermittlers: Marco Mielcarek

Ermittlertitel: Principal Investigator

Hat den Zugriff erweitert No
Bedingung Durchsuchen
Anzahl der Waffen 2
Armgruppe

Etikette: Related Donor

Art: Experimental

Beschreibung: PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -3 and intermediate-dose melphalan IV over 15-20 minutes on day -2. Patients also undergo low-dose TBI on day 0. TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID on days -3 to 80 with taper to day 180 (related donors) or on days -3 to 100 with taper to day 180 (unrelated donors). Patients also receive mycophenolate mofetil PO BID on days 0-27 (related donors) or TID on days 0-40 with taper to day 96 (unrelated donors).

Etikette: Unrelated Donor

Art: Experimental

Beschreibung: PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -3 and intermediate-dose melphalan IV over 15-20 minutes on day -2. Patients also undergo low-dose TBI on day 0. TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID on days -3 to 80 with taper to day 180 (related donors) or on days -3 to 100 with taper to day 180 (unrelated donors). Patients also receive mycophenolate mofetil PO BID on days 0-27 (related donors) or TID on days 0-40 with taper to day 96 (unrelated donors).

Studiendesign Info

Zuweisung: Non-Randomized

Interventionsmodell: Single Group Assignment

Hauptzweck: Treatment

Maskierung: None (Open Label)

Quelle: ClinicalTrials.gov