Busulfan, Melphalan, and Bortezomib Before First-Line Stem Cell Transplant in Treating Patients With Multiple Myeloma

NCT01605032 | Completed Phase 2 Results DMC

• 4 other identifiers: 11-12-434NCI-2013-0120711-102P30CA013330
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 4

Brief Summary

This phase II trial studies how well busulfan, melphalan, and bortezomib before first-line stem cell transplant works in treating patients with multiple myeloma. Giving chemotherapy before a peripheral blood stem cell transplant may stop the growth of cancer cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood and stored. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.

Conditions

DS Stage I Plasma Cell Myeloma; DS Stage II Plasma Cell Myeloma; DS Stage III Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (1)

• Rate of Complete Response as Determined by the IMWG Criteria

  Number of patients achieved complete response after the treatment regimen

  Day 100

Secondary Outcomes (5)

• Overall Response Rate

  Up to day 100

• Mortality

  Up to day 100

• Time-to-progression

  From start of treatment to disease progression with deaths, up to 2 years

• Progression-free Survival

  2 years

• Overall Survival

  2 years

Study Arms (1)

Treatment (busulfan, melphalan, bortezomib, autologous PBSCT)

EXPERIMENTAL

CONDITIONING: Patients receive busulfan IV over 3 hours on days -6 to -3, melphalan IV over 20 minutes on day -2, and bortezomib IV over 3-5 seconds on days -6, -3, 1, and 4. TRANSPLANT: Patients undergo autologous PBSCT on day 0.

Drug: Busulfan; Drug: Melphalan; Drug: Bortezomib; Procedure: Autologous Hematopoietic Stem Cell Transplantation; Procedure: Peripheral Blood Stem Cell Transplantation

Interventions

Busulfan DRUG

Given IV

Treatment (busulfan, melphalan, bortezomib, autologous PBSCT)

Melphalan DRUG

Given IV

Also known as: Alkeran

Treatment (busulfan, melphalan, bortezomib, autologous PBSCT)

Bortezomib DRUG

Given IV

Treatment (busulfan, melphalan, bortezomib, autologous PBSCT)

Autologous Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo autologous PBSCT

Also known as: Autologous Stem Cell Transplantation

Treatment (busulfan, melphalan, bortezomib, autologous PBSCT)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo autologous PBSCT

Also known as: PBPC transplantation, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplantation

Treatment (busulfan, melphalan, bortezomib, autologous PBSCT)

Eligibility Criteria

• Age: 18 Years - 72 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed multiple myeloma
• Measurable disease must be present as defined by protein criteria (quantifiable M-component in serum, urine or serum free light chains) in order to evaluate response as per IMWG; non-secretory patients are eligible provided the patient has \> 20% plasmacytosis OR multiple (\> 3) focal plasmacytomas or focal lesions on magnetic resonance imaging (MRI)
• Patients must have received induction chemotherapy for myeloma, but not more than 12 months of prior chemotherapy for this disease, and must be eligible for the first planned autologous transplant
• A minimum stem cell dose of 2.0 x 10\^6 cluster of differentiation 34-positive (CD34+) cells/kg has been collected
• Life expectancy of greater than 12 months
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Leukocytes \>= 3,000/mcL (unless myeloma related)
• Absolute neutrophil count \>= 1,500/mcL (unless myeloma related)
• Platelets \>= 50,000/mcL (unless myeloma related)
• Total bilirubin =\< 2 x institutional upper limit of normal unless 2nd to Gilbert's disease
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional upper limit of normal
• Creatinine =\< 1.5 x institutional upper limit of normal OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
• Ejection fraction by echocardiogram (ECHO) or multi gated acquisition scan (MUGA) \>= 40% performed within 60 days prior to registration
• Patients must have adequate pulmonary function studies: \> 50% of predicted on mechanical aspects (forced expiratory volume in one second \[FEV1\], forced vital capacity \[FVC\]) and diffusion capacity (diffusing capacity of the lung for carbon monoxide \[DLCO\]) \> 50% of predicted, within 60 days of registration; if the patients is unable to complete pulmonary function tests due to multiple myeloma (MM) related pain or condition, exception may be granted if the principal investigator (PI) documents that the patient is a candidate for high dose therapy
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for at least six months following the stem cell transplantation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Prior treatment history of autologous hematopoietic stem cell transplant (HSCT) or high-dose chemotherapy with stem cell rescue for any medical reason, not limited to myeloma treatment
• Patients may not be receiving any other investigational agents
• Patients with known brain metastases should be excluded from this clinical trial
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to or other agents used in the study, such as busulfan, melphalan, bortezomib, boron, or mannitol
• Grade 2 or greater peripheral neuropathy within 14 days prior to enrollment
• Unresolved grade \>= 3 non-hematologic toxicity from previous therapy; patients with grade 2 toxicity will be eligible at the discretion of the PI
• Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ; cancer treated with curative intent \< 5 years will not be allowed unless approved by the PI; cancer treated with curative intent \> 5 years will be allowed
• Patients must not have significant co-morbid medical condition
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; patients must not have suffered recent (\< 6 months) myocardial infarction, unstable angina, difficult to control congestive heart failure, uncontrolled hypertension, or difficult to control cardiac arrhythmias
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with busulfan
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
• Patients found to have an active hepatitis B infection (hepatitis B surface antigen +) are not eligible unless they meet ONE of the following criteria:
• Patient is able to start dual anti-hepatitis (Hep) B therapy prior to enrollment with adefovir and telbivudine
• Patient is already on dual anti-hepatitis B therapy

Sponsors & Collaborators

• Albert Einstein College of Medicine: lead
• National Cancer Institute (NCI): collaborator

Study Sites (4)

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

NYU Cancer Institute

New York, New York, 10016, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Busulfan; Melphalan; Bortezomib; Peripheral Blood Stem Cell Transplantation

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)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Ira Braunschweig, MD
• Organization: Albert Einstein College of Medicine/Montefiore Medical Center

IBRAUNSC@montefiore.org

718-920-4057

Study Officials

• Ira Braunschweig

  Albert Einstein College of Medicine

  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: March 7, 2012
• First Posted: May 24, 2012
• Study Start: February 1, 2012
• Primary Completion: March 1, 2018
• Study Completion: March 1, 2018
• Last Updated: August 20, 2020
• Results First Posted: August 20, 2020

Record last verified: 2020-08

Locations

US (4)