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

NCT01534143 | Terminated Phase 2 Results DMC

• 2 other identifiers: 2011-151NCI-2012-00120
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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

Conditions

Refractory Multiple Myeloma; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma

Outcome Measures

Primary Outcomes (4)

• 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.

  First 6 months post-transplant

• Time to Platelet Absolute Neutrophil Recovery (Engraftment)

  Estimated using Kaplan-Meier method.

  First 6 months post-transplant

• Treatment Related Mortality Defined as Death in Continuous or Complete Remission

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

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

• Grade III and IV Non Hematologic Toxicities

  Based on NCI CTCAE version 4.

  First 6 months post transplant

Secondary Outcomes (9)

• Incidence of Myeloma Progression

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

• Incidence of Transplant Related Mortality and Morbidity

  Up to 2 years post transplant

• Incidence of TTP

  Up to 2 years post transplant

• Incidence of SOS

  Up to 2 years post transplant

• Incidence and Severity of Chronic GVHD

  Up to 2 years post transplant

Study Arms (1)

Treatment (chemotherapy, enzyme inhibitor)

EXPERIMENTAL

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.

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

Interventions

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (chemotherapy, enzyme inhibitor)

tacrolimus DRUG

Given IV

Also known as: FK 506, Prograf

Treatment (chemotherapy, enzyme inhibitor)

sirolimus DRUG

Given PO

Also known as: AY 22989, Rapamune, rapamycin, SLM

Treatment (chemotherapy, enzyme inhibitor)

anti-thymocyte globulin BIOLOGICAL

Given IV

Also known as: ATG, ATGAM, lymphocyte immune globulin, Thymoglobulin

Treatment (chemotherapy, enzyme inhibitor)

fludarabine phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, Fludara

Treatment (chemotherapy, enzyme inhibitor)

busulfan DRUG

Given IV

Also known as: BSF, BU, Misulfan, Mitosan, Myeloleukon

Treatment (chemotherapy, enzyme inhibitor)

bortezomib DRUG

Given IV

Also known as: LDP 341, MLN341, VELCADE

Treatment (chemotherapy, enzyme inhibitor)

allogeneic hematopoietic stem cell transplantation PROCEDURE

Undergo allogeneic HSCT

Treatment (chemotherapy, enzyme inhibitor)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (chemotherapy, enzyme inhibitor)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Barbara Ann Karmanos Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Tacrolimus; Sirolimus; Antilymphocyte Serum; thymoglobulin; fludarabine phosphate; Busulfan; Bortezomib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Data was not collected, because funding was unavailable to continue study.

Results Point of Contact

• Title: Zaid Al-Kahdimi, M.D.
• Organization: Barbara Ann Karmanos Cancer Institute

zalkadh@emory.edu

(313) 576-8022

Study Officials

• Zaid Al-Kadhimi

  Barbara Ann Karmanos Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 13, 2012
• First Posted: February 16, 2012
• Study Start: February 1, 2012
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: April 5, 2017
• Results First Posted: December 16, 2013

Record last verified: 2017-03

Locations

US (1)