CompletedNCT00054353Updated Oct 16, 2017Results posted

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

A Phase 1/2 interventional study of fludarabine phosphate and melphalan in Refractory Multiple Myeloma, sponsored by Fred Hutchinson Cancer Center. Completed at 2 sites in 2 countries. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2017-10-16.

Sponsored by Fred Hutchinson Cancer Center · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 16
Allocation: Non-randomized
Ages: 18 Years to 70 Years
Sex: All

Study summary

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.

Read the detailed description

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.

Conditions studied

Refractory Multiple Myeloma

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Multiple Myeloma 3,712

In context

Multiple Myeloma

3,712 studies on the registry are indexed under Multiple Myeloma; 752 are open to participants now.

This study's enrollment of 16 is below the median of 41 across 2,965 interventional studies indexed under Multiple Myeloma.

Browse Multiple Myeloma studies →

Lead sponsor

Fred Hutchinson Cancer Center is the lead sponsor of 546 studies on the registry; 79 are open to participants now.

Of its 59 completed or terminated interventional studies of FDA-regulated products, 46 (78%) have results posted.

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Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 70 Years
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Single group
Masking: None (open label)
Enrollment: 16 participants (actual)

Study arms

Experimental
Related Donor
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).
Drug: fludarabine phosphate · Drug: melphalan · Radiation: total-body irradiation · Drug: mycophenolate mofetil · Drug: cyclosporine · Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation · Procedure: peripheral blood stem cell transplantation · Other: laboratory biomarker analysis
Experimental
Unrelated Donor
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).
Drug: fludarabine phosphate · Drug: melphalan · Radiation: total-body irradiation · Drug: mycophenolate mofetil · Drug: cyclosporine · Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation · Procedure: peripheral blood stem cell transplantation · Other: laboratory biomarker analysis

Interventions

Drugfludarabine phosphate
Given IV
Also known as: 2-F-ara-AMP, Beneflur, Fludara
Drugmelphalan
Given IV
Also known as: Alkeran, CB-3025, L-PAM, L-phenylalanine mustard, L-Sarcolysin
Radiationtotal-body irradiation
Undergo TBI
Also known as: TBI
Drugmycophenolate mofetil
Given PO
Also known as: Cellcept, MMF
Drugcyclosporine
Given PO
Also known as: ciclosporin, cyclosporin, cyclosporin A, CYSP, Sandimmune
Procedurenonmyeloablative allogeneic hematopoietic stem cell transplantation
Undergo reduced-intensity allogeneic PBSCT
Procedureperipheral blood stem cell transplantation
Undergo reduced-intensity allogeneic PBSCT
Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell
Otherlaboratory biomarker analysis
Correlative studies

What researchers measure

Primary outcomes

PFS
PFS will be calculated for all patients from the date of transplant until the time of progression, relapse, death, or the date the patient was last known to be in remission. Progressive disease is defined as greater than 25% increase in serum or urine M proteins compared to best response status after autologous transplant and/or appearance of new lytic bone lesions or plasmocytomas.
Time frame: At 1 year post-transplant
Non-relapse Mortality
Early NRM will be monitored in a sequential fashion.
Time frame: At day 100
Incidence of Acute GVHD (Grades III-IV)
Number of patients with Grade III-IV acute GVHD post-transplant. Severe GVHD will be monitored in a sequential fashion.
Time frame: Up to 5 years
Incidence of Chronic (Extensive) GVHD
Number of subjects with chronic extensive GVHD post-transplant. Severe GVHD will be monitored in a sequential fashion.
Time frame: Up to 5 years

Secondary outcomes

OS
Number of subjects surviving. OS will be estimated by the method of Kaplan and Meier. Confidence intervals will be estimated.
Time frame: At 6 months and then every year thereafter, up to 5 years
Engraftment
Number of subjects who engrafted post-transplant. Engraftment will be monitored in a sequential fashion.
Time frame: Up to 5 years
Relapse Rate
Number of subjects who relapsed after achieving CR post-transplant. Relapse rate will be summarized using cumulative incidence estimates.
Time frame: Up to 5 years
Response Rate
Number of subjects who achieved CR post-transplant. Response rate will be summarized using cumulative incidence estimates.
Time frame: Up to 5 years

Results

Posted Oct 16, 2017

Participant flow

Participant flow — Overall Study
Milestone	Related Donor	Unrelated Donor
Started	12	4
Completed	12	4
Not completed	0	0

Outcome measures

PrimaryPFS

PFS will be calculated for all patients from the date of transplant until the time of progression, relapse, death, or the date the patient was last known to be in remission. Progressive disease is defined as greater than 25% increase in serum or urine M proteins compared to best response status after autologous transplant and/or appearance of new lytic bone lesions or plasmocytomas.

Time frame:: At 1 year post-transplant
Reported as:: Count of participants · Participants

PFS
Participants	Related Donor	Unrelated Donor
PFS	4	1

PrimaryNon-relapse Mortality

Early NRM will be monitored in a sequential fashion.

Time frame:: At day 100
Reported as:: Count of participants · Participants

Non-relapse Mortality
Participants	Related Donor	Unrelated Donor
Non-relapse Mortality	1	1

PrimaryIncidence of Acute GVHD (Grades III-IV)

Number of patients with Grade III-IV acute GVHD post-transplant. Severe GVHD will be monitored in a sequential fashion.

Time frame:: Up to 5 years
Reported as:: Count of participants · Participants

Incidence of Acute GVHD (Grades III-IV)
Participants	Related Donor	Unrelated Donor
Incidence of Acute GVHD (Grades III-IV)	2	0

PrimaryIncidence of Chronic (Extensive) GVHD

Number of subjects with chronic extensive GVHD post-transplant. Severe GVHD will be monitored in a sequential fashion.

Time frame:: Up to 5 years
Reported as:: Count of participants · Participants

Incidence of Chronic (Extensive) GVHD
Participants	Related Donor	Unrelated Donor
Incidence of Chronic (Extensive) GVHD	4	1

SecondaryOS

Number of subjects surviving. OS will be estimated by the method of Kaplan and Meier. Confidence intervals will be estimated.

Time frame:: At 6 months and then every year thereafter, up to 5 years
Reported as:: Count of participants · Participants

OS
Participants	Related Donor	Unrelated Donor
6 Months	8	3
1 Year	5	2
2 Years	4	0
3 Years	3	0
4 Years	3	0
5 Years	3	0

SecondaryEngraftment

Number of subjects who engrafted post-transplant. Engraftment will be monitored in a sequential fashion.

Time frame:: Up to 5 years
Reported as:: Count of participants · Participants

Engraftment
Participants	Related Donor	Unrelated Donor
Engraftment	12	4

SecondaryRelapse Rate

Number of subjects who relapsed after achieving CR post-transplant. Relapse rate will be summarized using cumulative incidence estimates.

Time frame:: Up to 5 years
Reported as:: Count of participants · Participants

Relapse Rate
Participants	Related Donor	Unrelated Donor
Relapse Rate	1	1

SecondaryResponse Rate

Number of subjects who achieved CR post-transplant. Response rate will be summarized using cumulative incidence estimates.

Time frame:: Up to 5 years
Reported as:: Count of participants · Participants

Response Rate
Participants	Related Donor	Unrelated Donor
Response Rate	2	1

Adverse events

Collected over AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Related Donor	4/12 (33.3%)	4/12 (33.3%)	9/12 (75%)
Unrelated Donor	1/4 (25%)	1/4 (25%)	2/4 (50%)

Most frequent serious events

Most frequent serious events
Event	Related Donor	Unrelated Donor
Respiratory failureRespiratory, thoracic and mediastinal disorders	0/12	1/4
Adult respiratory distress syndromeRespiratory, thoracic and mediastinal disorders	2/12	0/4
Multi-organ failureGeneral disorders	2/12	0/4
Blood bilirubin increasedInvestigations	1/12	0/4

Most frequent other events

Showing 10 of 20

Most frequent other events
Event	Related Donor	Unrelated Donor
Acute kidney injuryRenal and urinary disorders	3/12	1/4
Blood bilirubin increasedInvestigations	1/12	1/4
Creatinine increasedInvestigations	1/12	1/4
HypotensionVascular disorders	1/12	1/4
HypoxiaRespiratory, thoracic and mediastinal disorders	1/12	1/4
Respiratory failureRespiratory, thoracic and mediastinal disorders	0/12	1/4
Supraventricular tachycardiaCardiac disorders	0/12	1/4
Adult respiratory distress syndromeRespiratory, thoracic and mediastinal disorders	1/12	0/4
Alanine aminotransferase increasedInvestigations	1/12	0/4
AnorexiaMetabolism and nutrition disorders	1/12	0/4

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Related Donor	Unrelated Donor	Total
<=18 years	0	0	0
Between 18 and 65 years	10	3	13
>=65 years	2	1	3

Sex: Female, Male
Sex: Female, Male(Participants)	Related Donor	Unrelated Donor	Total
Female	0	0	0
Male	12	4	16

Region of Enrollment
Region of Enrollment(participants)	Related Donor	Unrelated Donor	Total
United States	8	4	12
Italy	4	0	4

Study locations

2 sites

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington 98109, United States
University of Torino
Torino, 10126, Italy

Timeline

Tracking since Sep 25, 2026

Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Oct 2002, a primary completion of Oct 2009 and a completion of Oct 2012. It does not say whether these dates are actual or estimated.

Results were first posted in Oct 2017, 8 years after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered: Feb 5, 2003
First posted: Feb 6, 2003
Start: Oct 2002
Primary completionActual: Oct 2009
CompletionActual: Oct 14, 2012
Results first posted: Oct 16, 2017
Last update: Oct 16, 2017

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Oct 16, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00054353
Lead sponsor: Fred Hutchinson Cancer Center
Collaborators: National Cancer Institute (NCI)
Responsible party: Marco Mielcarek (Principal Investigator, Fred Hutchinson Cancer Center) — Principal investigator
First posted: Feb 6, 2003
Start date: Oct 2002
Primary completion: Oct 2009
Completion: Oct 14, 2012
Results posted: Oct 16, 2017
Last update: Oct 16, 2017

Study contacts

Marco Mielcarek

principal investigator · Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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Studies of the drugs tested here: Fludarabine phosphate · Melphalan · Mycophenolic Acid · Cyclosporine

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