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Refractory Multiple MyelomaPhase 2NCT01534143

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

A Phase 2 study testing pharmacological study, tacrolimus and sirolimus in people with Refractory Multiple Myeloma and Stage I Multiple Myeloma, run by Barbara Ann Karmanos Cancer Institute at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
pharmacological study, tacrolimus and sirolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteUnited States
Study dates
Feb 2012to May 2013
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201

Other trials in United States

About this study

Official title: A Pilot Study Using High Dose Busulfan and Bortezomib as Part of Allogeneic Transplant Conditioning Regimen for High Risk Multiple Myeloma Patients.

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

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

  1. Incidence of opportunistic infections including cytomegalovirus (CMV), herpes simplex virus (HSV), and Epstein-Barr virus (EBV) reactivation.
  2. 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.

Being tested
pharmacological study, tacrolimus, sirolimus, anti-thymocyte globulin, fludarabine phosphate
Medical subject headings
Multiple Myeloma

What participants receive

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

Study groups in NCT01534143
Study groupRoleWhat they receive
Treatment (chemotherapy, enzyme inhibitor)ExperimentalCONDITIONING 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.
Receives: 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

What is being measured

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

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

    Graded using the Glucksberg scale. Proportions and confidence intervals will be estimated. Estimated using binary proportion estimates as well as competing risk method.

    Measured: First 6 months post-transplant

  2. Time to Platelet Absolute Neutrophil Recovery (Engraftment)

    Estimated using Kaplan-Meier method.

    Measured: First 6 months post-transplant

  3. Treatment Related Mortality Defined as Death in Continuous or Complete Remission

    Based on National Cancer Institute (NCI) CTCAE version 4.

    Measured: From the date of transplant to the date of death, assessed up to 6 months post transplant

  4. Grade III and IV Non Hematologic Toxicities

    Based on NCI CTCAE version 4.

    Measured: First 6 months post transplant

Secondary outcomes (9)

  1. Incidence of Myeloma Progression

    Measured: Time to the first observation of disease progression/relapse post transplant, assessed up to 2 years post transplant

  2. Incidence of Transplant Related Mortality and Morbidity

    Measured: Up to 2 years post transplant

  3. Incidence of TTP

    Measured: Up to 2 years post transplant

  4. Incidence of SOS

    Measured: Up to 2 years post transplant

  5. Incidence and Severity of Chronic GVHD

    Measured: Up to 2 years post transplant

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

    Measured: Weekly to day 100

  7. Overall Survival

    Measured: Up to 2 years post transplant

  8. Progression Free Survival

    Measured: From the day of transplant to progression, death, or last contact, assessed up to 2 years

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

    Measured: Days 30, 60, 90, and at 6 months after transplant

Timeline

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

  1. First posted16 Feb 2012 (estimated)
  2. Study startFeb 2012
  3. Primary completionMay 2013
  4. Study completionMay 2013

Why it stopped: Data was not collected, because funding was unavailable to continue study.

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01534143
Sponsor's protocol ID
2011-151
Other IDs
NCI-2012-00120
Status last verified
Mar 2017
First submitted
13 Feb 2012
Last updated
5 Apr 2017
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing pharmacological study, tacrolimus and sirolimus in people with Refractory Multiple Myeloma and Stage I Multiple Myeloma, run by Barbara Ann Karmanos Cancer Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 5 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Dec 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01534143.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2017; AzTrials last refreshed its copy on 7 Nov 2026.

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