NCT01534143 · REGISTRY CONDITION SEARCH

High Dose Busulfan and Bortezomib in Treating Patients With High Risk Multiple Myeloma Undergoing Stem Cell Transplant

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE2
Status at capture: TERMINATED
Registry last update: 2017-04-05

This pilot phase II trial studies how well giving high dose busulfan together with bortezomib works in treating patients with high risk multiple myeloma undergoing stem cell transplant. Drugs used in chemotherapy, such as busulfan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cells growth. Giving busulfan together with bortezomib before a stem cell transplant may kill more cancer cells

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Incidence and Severity of Acute GVHD Using Fludarabine Phosphate / Busulfan / Bortezomib Preparative Regimen and Triple Immune Suppression With Tacrolimus, Sirolimus and Anti-thymocyte Globulin

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outcome · POSTED

Time to Platelet Absolute Neutrophil Recovery (Engraftment)

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outcome · POSTED

Treatment Related Mortality Defined as Death in Continuous or Complete Remission

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outcome · POSTED

Grade III and IV Non Hematologic Toxicities

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outcome · POSTED

Incidence of Myeloma Progression

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outcome · POSTED

Incidence of Transplant Related Mortality and Morbidity

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outcome · POSTED

Incidence of TTP

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outcome · POSTED

Incidence of SOS

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outcome · POSTED

Incidence and Severity of Chronic GVHD

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outcome · POSTED

Incidence of Opportunistic Infections Including CMV, HSV, and EBV Reactivation

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outcome · POSTED

Overall Survival

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outcome · POSTED

Progression Free Survival

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outcome · POSTED

Recovery of T-cell, B Cell and NK Cell Phenotypes

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Ability to provide informed consent * Karnofsky Performance Status (KPS) \>= 70 * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 * Availability of a suitable allogeneic hematopoietic stem cell donor; minimum of human leukocyte antigen (HLA) 7/8 matched related or unrelated donor * High risk multiple myeloma with poor prognostic features based on having one or more of the following criteria: * Progressive disease after autologous transplant. No less than 3 months post auto transplant * Progressive or stable disease after induction chemotherapy using the most potent myeloma agents Lenalidomide and/or Bortezomib * Patients with high risk cytogenetic abnormalities documented on conventional cytogenetics or fluorescence in situ hybridization (FISH) (hypodiploidy, t(4:14), t(14:16) chromosome translocation, p53 and or complex cytogenetics) additionally, chromosome 13 deletion by standard cytogenetics * Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test for women, as well as implementation of birth control for men and women Exclusion Criteria: * Patients with prior allogeneic transplant, or more than one prior autologous transplant for any medical reason * Prior treatment with busulfan or gemtuzumab (Mylotarg ®) for any reason * Patient with history of allergy to boron, mannitol, or bortezomib * Creatinine clearance (CrCl) =\< 50 ml/min * Ejection Fraction \< 50% * Diffusion capacity of carbon monoxide (DLCO) \< 50% predicted * Forced expiratory volume in 1 second (FEV1) \< 50% predicted * Forced vital capacity (FVC) \< 50% predicted * Patients with uncontrolled arrhythmia or uncontrolled heart disease at the screening time; patients with coronary heart disease (recent myocardial infarctions, angina, cardiac stent, or bypass surgery in the last 6 months) need to be cleared with a stress echo or nuclear myocardial perfusion stress test, and cardiology consult; all other cardiac history will be at the discretion of the principal investigator * Liver enzymes \> 3 times upper limit normal * Bilirubin \> 2 mg/dl (except Gilbert's disease) * International normalized ratio (INR) \> 2 * Any previous history of liver failure, hepatitis, or cirrhosis * Systemic Amyloidosis Known history of hepatitis B, C, human immunodeficiency virus (HIV) or any current uncontrolled infection * Grade \> I neuropathy * Women who are pregnant or lactating * Current or history of alcohol or drug abuse * Use of other investigational agents within 30 days of enrollment to this study * Any patient with ascites * Any patient on home oxygen * Any clinical findings on history or physical exam which would in the opinion of the treating physician or principal investigator preclude the patient from participating in the study
healthy Volunteers: false
maximum Age: 70 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -7 to -3, busulfan IV on days -6 to -3, and bortezomib IV on day -2. GVHD PROPHYLAXIS: Patients receive thymoglobulin IV on days -3 to -1, sirolimus PO on day -3, and tacrolimus IV on day -3. Patients undergo allogeneic HSCT on day 0.
intervention Names
Other: pharmacological study
Drug: tacrolimus
Drug: sirolimus
Biological: anti-thymocyte globulin
Drug: fludarabine phosphate
Drug: busulfan
Drug: bortezomib
Procedure: allogeneic hematopoietic stem cell transplantation
Other: laboratory biomarker analysis
label
Treatment (chemotherapy, enzyme inhibitor)
type
EXPERIMENTAL

interventions

arm Group Labels
Treatment (chemotherapy, enzyme inhibitor)
description
Correlative studies
name
pharmacological study
other Names
pharmacological studies
type
OTHER
arm Group Labels
Treatment (chemotherapy, enzyme inhibitor)
description
Given IV
name
tacrolimus
other Names
FK 506
Prograf
type
DRUG
arm Group Labels
Treatment (chemotherapy, enzyme inhibitor)
description
Given PO
name
sirolimus
other Names
AY 22989
Rapamune
rapamycin
SLM
type
DRUG
arm Group Labels
Treatment (chemotherapy, enzyme inhibitor)
description
Given IV
name
anti-thymocyte globulin
other Names
ATG
ATGAM
lymphocyte immune globulin
Thymoglobulin
type
BIOLOGICAL
arm Group Labels
Treatment (chemotherapy, enzyme inhibitor)
description
Given IV
name
fludarabine phosphate
other Names
2-F-ara-AMP
Beneflur
Fludara
type
DRUG
arm Group Labels
Treatment (chemotherapy, enzyme inhibitor)
description
Given IV
name
busulfan
other Names
BSF
BU
Misulfan
Mitosan
Myeloleukon
type
DRUG
arm Group Labels
Treatment (chemotherapy, enzyme inhibitor)
description
Given IV
name
bortezomib
other Names
LDP 341
MLN341
VELCADE
type
DRUG
arm Group Labels
Treatment (chemotherapy, enzyme inhibitor)
description
Undergo allogeneic HSCT
name
allogeneic hematopoietic stem cell transplantation
type
PROCEDURE
arm Group Labels
Treatment (chemotherapy, enzyme inhibitor)
description
Correlative studies
name
laboratory biomarker analysis
type
OTHER

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 1
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Graded using the Glucksberg scale. Proportions and confidence intervals will be estimated. Estimated using binary proportion estimates as well as competing risk method.
measure
Incidence and Severity of Acute GVHD Using Fludarabine Phosphate / Busulfan / Bortezomib Preparative Regimen and Triple Immune Suppression With Tacrolimus, Sirolimus and Anti-thymocyte Globulin
time Frame
First 6 months post-transplant
description
Estimated using Kaplan-Meier method.
measure
Time to Platelet Absolute Neutrophil Recovery (Engraftment)
time Frame
First 6 months post-transplant
description
Based on National Cancer Institute (NCI) CTCAE version 4.
measure
Treatment Related Mortality Defined as Death in Continuous or Complete Remission
time Frame
From the date of transplant to the date of death, assessed up to 6 months post transplant
description
Based on NCI CTCAE version 4.
measure
Grade III and IV Non Hematologic Toxicities
time Frame
First 6 months post transplant

secondary Outcomes

measure
Incidence of Myeloma Progression
time Frame
Time to the first observation of disease progression/relapse post transplant, assessed up to 2 years post transplant
measure
Incidence of Transplant Related Mortality and Morbidity
time Frame
Up to 2 years post transplant
measure
Incidence of TTP
time Frame
Up to 2 years post transplant
measure
Incidence of SOS
time Frame
Up to 2 years post transplant
measure
Incidence and Severity of Chronic GVHD
time Frame
Up to 2 years post transplant
measure
Incidence of Opportunistic Infections Including CMV, HSV, and EBV Reactivation
time Frame
Weekly to day 100
measure
Overall Survival
time Frame
Up to 2 years post transplant
measure
Progression Free Survival
time Frame
From the day of transplant to progression, death, or last contact, assessed up to 2 years
measure
Recovery of T-cell, B Cell and NK Cell Phenotypes
time Frame
Days 30, 60, 90, and at 6 months after transplant

Full study description

brief Summary: This pilot phase II trial studies how well giving high dose busulfan together with bortezomib works in treating patients with high risk multiple myeloma undergoing stem cell transplant. Drugs used in chemotherapy, such as busulfan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cells growth. Giving busulfan together with bortezomib before a stem cell transplant may kill more cancer cells
detailed Description: PRIMARY OBJECTIVES: I. To determine time to engraftment absolute neutrophil count (\> 0.5 x 10\^9/L for 3 consecutive days), and platelet (\> 20X 109\^/L for 3 consecutive days). 2\. Incidence and severity of acute graft-versus-host disease (GVHD) using fludarabine (fludarabine phosphate) / busulfan / bortezomib preparative regimen and triple immune suppression with tacrolimus, sirolimus and Thymoglobulin (anti-thymocyte globulin). 3\. To determine the safety related to this combination in the first six months post transplant, specifically, treatment related mortality and grade III and IV non hematologic toxicities, based on Common Terminology Criteria for Adverse Events (CTCAE) version 4 (v4). SECONDARY OBJECTIVES: I. Incidence of myeloma progression in this high risk group of patients. II. Incidence of transplant related mortality and morbidity. III. Incidence of thrombotic thrombocytopenic purpura (TTP) and sinusoidal obstructive syndrome (SOS). IV. Incidence and severity of chronic GVHD. V. Incidence of opportunistic infections including cytomegalovirus (CMV), herpes simplex virus (HSV), and Epstein-Barr virus (EBV) reactivation. I. Overall and progression free survival (PFS) at Day 100, 6 months, 1 \& 2 years post transplant. VII. To determine recovery of T-cell, B cell, and natural killer (NK) cell phenotypes post transplant. OUTLINE: CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -7 to -3, busulfan IV on days -6 to -3, and bortezomib IV on day -2. GVHD PROPHYLAXIS: Patients receive anti-thymocyte globulin IV on days -3 to -1, sirolimus orally (PO) on day -3, and tacrolimus IV on day -3. Patients undergo allogeneic hematopoietic stem cell transplantation (HSCT) on day 0. After completion of study treatment, patients are followed up for up to 2 years.

Source references

Source notices and limitations

Discovery and provenance

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Preserved source evidence · Not medical advice