Autologous Hematopoietic Stem Cell Transplant RecipientPhase 1NCT01163357

Bortezomib, Total Marrow Irradiation, Fludarabine Phosphate, and Melphalan in Treating Patients Undergoing Donor Peripheral Blood Stem Cell Transplant For High-Risk Stage I or II Multiple Myeloma

A Phase 1 study testing bortezomib, fludarabine phosphate and melphalan in people with Autologous Hematopoietic Stem Cell Transplant Recipient and Loss of Chromosome 17p, run by City of Hope Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Autologous Hematopoietic Stem Cell Transplant Recipient, Loss of Chromosome 17p, Plasma Cell Leukemia
What is being tested?: bortezomib, fludarabine phosphate and melphalan
Type of treatment: Pill or oral medicine, Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 18 participants
Where: 1 siteUnited States
Study dates: 1 Mar 2011to 20 May 2024
Phase: Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Recipient must have signed a voluntary, informed consent in accordance with institutional and federal guidelines
Recipients must have histopathologically confirmed diagnosis of multiple myeloma
Age:
Stratum I (TMI containing arm): 18-60 years of age
Stratum II (non TMI arm): 18-70 years of age
Patients with primary progressive disease on induction therapy with new targeted therapies

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Relapsed/refractory disease on new targeted therapies, i.e. thalidomide, lenalidomide, bortezomib, or other new novel agents such as carfilzomib, pomalidomide
Patients with relapsed multiple myeloma following previous autologous stem cell transplant
Plasma cell leukemia at diagnosis
High-risk patients with presence of chromosome 17p deletion (> 60%) in the bone marrow by fluorescence in situ hybridization (FISH); patients are not required to have prior autologous stem cell transplant
Able to lie supine for approximately 60 minutes, the anticipated duration of each treatment session
Performance status evaluated by Eastern Cooperative Oncology Group (ECOG) or Karnofsky Performance Scales (KPS) patients must have a score of 0-II (ECOG) or >= 70% (KPS)
Cardiac ejection fraction >= 50% by multiple gate acquisition (MUGA) scan and/or by echocardiogram
Forced expiratory volume in one second (FEV1) >= 50%
Diffusing lung capacity for carbon monoxide (DLCO) >= 50%
Creatinine clearance or glomerular filtration rate (GFR) >= 60 ml/min
Serum bilirubin =< 2.0 mg/dl
Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) =< 2.5 times the institutional upper limits of normal
Pre-treatment tests must be performed within 30 days prior to enrollment
No other medical and or psychosocial problems, which in the opinion of the primary physician or principal investigator would place the patient at unacceptable risk from this regimen
Patients with no previous radiation or up to a maximum 2000 cGy to non thoracic-spine and rib bone lesions or < 20% of bone marrow are eligible for TMI conditioning regimen
Patients with previous history of irradiation at any dose to thoracic-spine, ribs or >= 20% of bone marrow cannot undergo TMI and will be eligible for bortezomib, fludarabine, and melphalan regimen
Stratum II); patients can be enrolled on stratum II at their physician's discretion or if patients decline radiation therapy
DONOR: Any matched sibling donor (matched at HLA A, B, C by intermediate resolution typing and HLA-DRB1 by high resolution typing), or unmatched unrelated donor (matched at HLA A, B, C, DRB1 by high resolution typing) will be considered a suitable donor

Who cannot join

Patients with peripheral neuropathy greater than grade II
Major medical or psychiatric disorders that would seriously compromise patient tolerance of this regimen
Human immunodeficiency virus (HIV) infection, active hepatitis B or C infection, or evidence of liver cirrhosis
Active viral, bacterial or fungal infection unless adequately treated. For fungal infection, patient should have completed full course of antifungal therapy with resolution of infection.
Patients with radiographic changes including pulmonary disease, including but not limited to: pulmonary nodules, infiltrates, pleural effusion are excluded unless cleared by pulmonary biopsy showing no evidence for pulmonary infection
Patients with renal insufficiency or cr clearance < 60 ml/min
DONOR: Donors will be excluded if for medical or psychological reasons they are unable to tolerate the procedure of peripheral stem cell donation

Trial locations and contacts

1 site in 1 country.

United States1 site

City of Hope
Duarte, California, 91010

Other trials in United States

About this study

Official title: Phase I Study of Bortezomib With or Without Total Marrow Irradiation (TMI) Using Intensity Modulated Radiation Therapy (IMRT) in Combination With Fludarabine (FLU) and Melphalan (MEL) as a Preparative Regimen for Allogeneic Hematopoietic Stem Cell (HSC) Transplantation in Patients With High Risk Multiple Myeloma

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving chemotherapy drugs, such as fludarabine phosphate and melphalan, and total marrow irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given together with fludarabine phosphate and melphalan with or without total marrow irradiation in treating patients undergoing donor peripheral blood stem cell transplant for high-risk stage I or II multiple myeloma.

Read the detailed description

PRIMARY OBJECTIVES:

To determine the feasibility of escalating doses of bortezomib with or without total marrow irradiation (TMI) at a fixed dose of 900 cGy in combination with fludarabine (FLU) and melphalan (MEL) as preparative regimen for allogeneic hematopoietic stem cell transplant in patients with high risk multiple myeloma who have human leukocyte antigen (HLA) matched donor (sibling or matched unrelated donor).

II. To describe toxicities, maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of this preparative regimen.

SECONDARY OBJECTIVES:

To evaluate the frequency of clinical response, i.e., complete response [CR], partial response [PR], very good partial response [VGPR]) at 6 month and 1 year post transplant.

II. To evaluate the frequency of primary and secondary engraftment failure.

III. To evaluate the time to neutrophil and platelet engraftment.

IV. To evaluate the incidence of acute and chronic graft-versus-host disease (GVHD).

To evaluate progression-free survival.

VI. To evaluate overall survival.

VII. To evaluate minimal residual disease (MRD) at 6 months and 1 year post transplant by flow cytometry in the bone marrow.

OUTLINE: This is a dose-escalation study of bortezomib. Patients are assigned to 1 of 2 treatment groups. GROUP I (patients eligible for TMI): Patients receive fludarabine phosphate intravenously (IV) on days -9 to -5 and melphalan IV on day -4. Patients also undergo TMI twice daily (BID) on days -9 to -7. If no DLT is observed in the first cohort, bortezomib IV will be added on days -6 and -3 for subsequent cohorts. GROUP II (patients ineligible for TMI): Patients receive fludarabine phosphate IV and melphalan IV as in Group I. Patients also receive bortezomib IV on days -6, -3, 1, and 4.

TRANSPLANT: All patients undergo allogeneic peripheral blood stem cell (PBSC) transplant on day 0.

GVHD PROPHYLAXIS: All patients receive tacrolimus IV or orally (PO) and sirolimus PO beginning on day -3.

After completion of study treatment, patients are followed up at day 100, 6 months, and then annually thereafter for up to 4 years.

Conditions: Autologous Hematopoietic Stem Cell Transplant Recipient, Loss of Chromosome 17p, Plasma Cell Leukemia, Recurrent Plasma Cell Myeloma, Refractory Plasma Cell Myeloma
Being tested: bortezomib, fludarabine phosphate, melphalan, total marrow irradiation, tacrolimus
Medical subject headings: Chromosome 17 deletion, Leukemia, Plasma Cell, Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

bortezomibDrug
Also called LDP 341, MLN341, PS-341, VELCADE
Given IV
fludarabine phosphateDrug
Also called 2-F-ara-AMP, Beneflur, Fludara
Given IV
melphalanOther
Also called Alkeran, CB-3025, L-PAM, L-phenylalanine mustard
Given IV
total marrow irradiationRadiation
Undergo TMI
tacrolimusDrug
Also called Advagraf, FK 506, Prograf, Protopic
Given IV and orally
sirolimusDrug
Also called AY 22989, RAPA, Rapamune, rapamycin
Given orally
peripheral blood stem cell transplantationProcedure or surgery
Also called PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell
Undergo allogeneic PBSC transplant
laboratory biomarker analysisOther
Correlative studies

Study groups in NCT01163357
Study group	Role	What they receive
Group I (bortezomib, fludarabine phosphate, TMI, melphalan)	Experimental	Patients receive fludarabine phosphate IV on days -9 to -5 and melphalan IV on day -4. Patients also undergo TMI BID on days -9 to -7. If no DLT is observed in the first cohort, bortezomib IV will be added on days -6 and -3 for subsequent cohorts. Receives: Drug: bortezomib; Drug: fludarabine phosphate; Other: melphalan; Radiation: total marrow irradiation; Drug: tacrolimus; Drug: sirolimus; Procedure: peripheral blood stem cell transplantation; Other: laboratory biomarker analysis
Group II (bortezomib, fludarabine phosphate, melphalan	Experimental	Patients receive fludarabine phosphate IV and melphalan IV as in Stratum I. Patients also receive bortezomib IV on days -6, -3, 1, and 4. Receives: Drug: bortezomib; Drug: fludarabine phosphate; Other: melphalan; Drug: tacrolimus; Drug: sirolimus; Procedure: peripheral blood stem cell transplantation; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum tolerated dose of bortezomib as defined as the highest dose tested in which none or only one patient experiences dose limiting toxicity attributable to the study regimen
Assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Dose-limiting toxicity will be defined using Bearman Scale for events that occur.
Measured: 6 weeks post transplant
Feasibility of escalating doses of bortezomib with or without TMI in combination with FLU and MEL as preparative regimen for allogeneic hematopoietic stem cell transplant in patients with high risk multiple myeloma
Measured: 5 years post transplant

Secondary outcomes (7)

Frequency of clinical response (i.e., complete, partial, or very good partial response)
Response is evaluated based on a new International myeloma working group uniform response criteria.
Measured: At 6 months and 1 year post transplant
Frequency of primary and secondary engraftment failure
Measured: 6 weeks post transplant and 4 years post transplant
Time to neutrophil and platelet engraftment
Measured: 100 days post transplant
Progression-free survival
Time from day 0 of transplant to the first observation or relapse or death due to any cause, assessed up to 4 years
Measured: 4 years post transplant
Incidence of acute and chronic graft-versus-host disease
Measured: At 6 months and 1 year post transplant up to 4 years post transplant
Overall survival
Time from first day of treatment to time of death due to any cause, assessed up to 4 years
Measured: 4 years post transplant
Minimal residue disease
Assessed by flow cytometry
Measured: At 6 months and 1 year post transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Mar 201120 May 2024

First posted15 Jul 2010 (estimated)
Study start1 Mar 2011
Primary completion20 Jul 2019
Study completion20 May 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Autologous Hematopoietic Stem Cell Transplant RecipientStudies of the same condition, open and under way.
More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 18 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01163357
Sponsor's protocol ID: 09171
Other IDs: NCI-2010-01610
Status last verified: Oct 2026
First submitted: 14 Jul 2010
Last updated: 22 Oct 2026
Results posted: No
Data monitoring committee: Yes