High-Dose Gemcitabine, Busulfan and Melphalan With Hematopoietic-Cell Support for Patients With Poor-Risk Myeloma

NCT01237951 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2010-0506NCI-2012-01906
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if the combination of gemcitabine, busulfan, and melphalan, when given before a stem cell transplant, can help to control refractory myeloma. The safety of this study treatment will also be studied.

Conditions

Myeloma

Keywords

Autologous Hematopoietic-Cell Support; Stem Cell Transplant; Busulfan; Myleran; Busulfex; Gemcitabine; Gemzar; Melphalan; Alkeran; Decadron; Dexamethasone; G-CSF; Filgrastim; Neupogen

Outcome Measures

Primary Outcomes (1)

• Participants Who Had Measurable Disease at Time of Transplant and Achieved a Stringent Complete Remission

  Stringent complete remission was defined as negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, 5% or fewer plasma cells in bone marrow, normal free light chain ratio, and the absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence.

  100 days post-transplant

Secondary Outcomes (3)

• Progression-free Survival (PFS)

  From date of transplant until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years.

• Overall Survival

  From date of transplant until the date of death from any cause, assessed up to 2 years

• Percent of Participants Dying From Treatment-Related Complications

  From date of transplant until the date of death from treatment-related complications, assessed up to 2 years

Study Arms (1)

GemBuMel

EXPERIMENTAL

Gemcitabine 1875 mg/m\^2 IV (75 mg/ m2 bolus followed by 1800 mg/m\^2 over 3 hours) on Day -8 and Day -3 as an outpatient or inpatient. Busulfan 32 mg/m2 test dose with PKs as outpatient before Day -12, or as an inpatient on Day -10. Busulfan area under curve (AUC) 4,000 by vein on Days -8 to -5 as an outpatient or inpatient. Melphalan 60 mg/m\^2 IV on Days -3 and -2 over 30 minutes on both days as an outpatient or inpatient. Palifermin 60 micrograms/kg infused as an IVP (by vein) over 15-30 seconds Days -12 to -10 and Days 0 to +2 as an outpatient. Palifermin 60 micrograms/kg by vein on Days -13 to -11 and on Days 0, +1 and +2 as in inpatient. Dexamethasone 8 mg IV twice a day by vein over 15 minutes Days -9 through -2 as an outpatient or inpatient. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +5 and continuing until neutrophil recovery is documented. Stem Cell Transplant: On Day 0, stem cells returned to body by vein over 30-60 minutes.

Drug: Palifermin; Drug: Dexamethasone; Drug: Gemcitabine; Drug: Busulfan; Drug: Melphalan; Procedure: Stem Cell Transplant; Drug: G-CSF

Interventions

Palifermin DRUG

60 micrograms/kg infused as an IVP (by vein) over 15-30 seconds Days -12 to -10 and Days 0 to +2 as an outpatient. 60 micrograms/kg by vein on Days -13 to -11 and on Days 0, +1 and +2 as in inpatient.

Also known as: kepivance

GemBuMel

Dexamethasone DRUG

8 mg IV twice a day by vein over 15 minutes Days -9 through -2 as an outpatient or inpatient.

Also known as: decadron

GemBuMel

Gemcitabine DRUG

1875 mg/m\^2 IV (75 mg/ m2 bolus followed by 1800 mg/m\^2 over 3 hours) on Day -8 and Day -3 as an outpatient or inpatient.

Also known as: Gemcitabine Hydrochloride, Gemzar

GemBuMel

Busulfan DRUG

32 mg/m2 test dose with PKs as outpatient before Day -12, or as an inpatient on Day -10. Busulfan AUC 4,000 by vein on Days -8 to -5 as an outpatient or inpatient.

Also known as: myleran, busulfex

GemBuMel

Melphalan DRUG

60 mg/m\^2 IV on Days -3 and -2 over 30 minutes on both days as an outpatient or inpatient.

Also known as: Alkeran

GemBuMel

Stem Cell Transplant PROCEDURE

On Day 0, stem cells returned to body by vein over 30-60 minutes.

Also known as: SCT, ASCT

GemBuMel

G-CSF DRUG

5 mcg/kg/day subcutaneously beginning on Day +5 and continuing until neutrophil recovery is documented.

Also known as: Filgrastim, Neupogen

GemBuMel

Eligibility Criteria

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

You may qualify if:

• Age 18 to 70 years.
• Patients with myeloma treated with first-line therapy including lenalidomide, bortezomib or thalidomide, and one or more of the following: 2.1) M paraprotein greater than 1 g/dL at HDC. 2.2) Less than partial response to first-line therapy. 2.3) Relapse after first-line therapy. 2.4) Relapse after a prior autologous stem-cell transplant.
• Adequate renal function, as defined by serum creatinine \</=1.8 mg/dL and/or estimated serum creatinine clearance \>/=50 ml/min
• Adequate hepatic function, as defined by serum glutamate oxaloacetate transaminase (SGOT) and/or serum glutamate pyruvate transaminase (SGPT) \</=3 x upper limit of normal; serum bilirubin and alkaline phosphatase \</=2 x upper limit of normal, unless proven to be due to disease involvement.
• Adequate pulmonary function with forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and diffusing capacity of lung for carbon monoxide (DLCO) \>/=50% of expected corrected for hemoglobin and/or volume.
• Adequate cardiac function with left ventricular ejection fraction \>/=40%. No uncontrolled arrhythmias or symptomatic cardiac disease.
• Zubrod performance status \<2.
• Negative Beta human chorionic gonadotropin (HCG) text in a woman with child-bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization

You may not qualify if:

• Patients with grade \>/= 3 non-hematologic toxicity from previous therapy that has not resolved to \</= grade 1.
• Patients with prior whole brain irradiation
• Patients with active hepatitis B, either active carrier (HBsAg +) or viremic (HBV DNA \>/=10,000 copies/mL, or \>/= 2,000 IU/mL).
• Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic hepatitis C or positive hepatitis C serology.
• Active infection requiring parenteral antibiotics.
• HIV infection, unless the patient is receiving effective antiretroviral therapy with undetectable viral load and normal cluster of differentiation 4 (CD4) counts
• Patients having received radiation therapy to head and neck (excluding eyes), and internal organs of chest, abdomen or pelvis in the month prior to enrollment.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Nieto Y, Valdez BC, Pingali SR, Bassett R, Delgado R, Nguyen J, Shah N, Popat U, Jones RB, Andersson BS, Gulbis A, Ahmed S, Bashir Q, Parmar S, Patel K, Myers A, Rondon G, Orlowski RZ, Champlin R, Qazilbash M. High-dose gemcitabine, busulfan, and melphalan for autologous stem-cell transplant in patients with relapsed or refractory myeloma: a phase 2 trial and matched-pair comparison with melphalan. Lancet Haematol. 2017 Jun;4(6):e283-e292. doi: 10.1016/S2352-3026(17)30080-7. Epub 2017 May 15.

  PMID: 28522110 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Neoplasms, Plasma Cell

Interventions

Fibroblast Growth Factor 7; Dexamethasone; Calcium Dobesilate; Gemcitabine; Busulfan; Melphalan; Stem Cell Transplantation; Granulocyte Colony-Stimulating Factor; Filgrastim

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Fibroblast Growth Factors; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines

Results Point of Contact

• Title: Dr. Nieto, Yago, M.D./Stem Cell Transplantation
• Organization: UT MD Anderson Cancer Center

ynieto@mdanderson.org

713-792-2466

Study Officials

• Yago Nieto, MD, PhD

  M.D. Anderson Cancer Center

  STUDY CHAIR

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: SPONSOR

Study Record Dates

• First Submitted: November 8, 2010
• First Posted: November 10, 2010
• Study Start: November 8, 2010
• Primary Completion: September 20, 2017
• Study Completion: September 20, 2017
• Last Updated: May 5, 2020
• Results First Posted: May 5, 2020

Record last verified: 2020-04

Locations

US (1)