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MyelomaPhase 2NCT01237951

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

A Phase 2 study testing Palifermin, Dexamethasone and Gemcitabine in people with Myeloma, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Myeloma
What is being tested?
Palifermin, Dexamethasone and Gemcitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
75 participants
Where
1 siteUnited States
Study dates
8 Nov 2010to 20 Sep 2017
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

  • 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

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: High-dose Gemcitabine, Busulfan and Melphalan With Autologous Hematopoietic-Cell Support for Patients With Poor-Risk Myeloma

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.

Read the detailed description

Study Drugs:

Busulfan and melphalan are designed to bind to the DNA (genetic material) of cells, which may cause cancer cells to die. They are commonly used in stem cell transplantation.

Gemcitabine is designed to disrupt the growth of cancer cells, which may cause cancer cells to die. It may help to increase the effect of busulfan and melphalan on cancer cells by not allowing these cells to repair the DNA damage caused by busulfan or melphalan.

Busulfan Test Dose:

You will receive a test dose of busulfan by vein over about 60 minutes. This low-level test dose of busulfan is to check how the level of busulfan in your blood levels changes over time. This information will be used to decide the next dose needed to reach the target blood level that matches your body size. You will most likely receive this as an outpatient during the week before you are admitted to the hospital. If it cannot be given as an outpatient, you will be admitted to the hospital on Day -11 (11 days before your stem cells are returned to your body) and the test dose will be given on Day -10.

About 11 samples of blood (about 1 teaspoon each time) will be drawn for pharmacokinetic (PK) testing. PK testing measures the amount of study drug in the body at different time points and will help the study doctor determine what your dose of busulfan should be on study. These blood samples will be drawn at various timepoints before you receive busulfan and over about the next 11 hours. The blood samples will be repeated again on the first day of high-dose busulfan treatment Day -8. A temporary heparin lock line will be placed in your vein to lower the number of needle sticks needed for these draws. If it is not possible for the PK tests to be performed, you will receive the standard dose of busulfan.

If you receive the busulfan test dose as an outpatient:

On Days -12 (12 days before your stem cells are returned to your body) through Day -10, you will receive palifermin by vein over about 30 seconds to help decrease the risk of side effects in the mouth and throat.

You will be admitted on Day -9 and will receive fluids by vein to hydrate you. You will swish the liquids caphosol and glutamine in your mouth 4 times a day, for about 2 minutes each time. You will swish these liquids every day until you leave the hospital. These drugs are also used to help decrease the risk of side effects in the mouth and throat.

On Days -8 through -5, you will receive busulfan by vein over about 3 hours.

On Days -8 and -3, you will receive gemcitabine by vein over about 3 hours.

On Day -4, you will not receive any drugs.

If you receive the busulfan test dose as an inpatient:

On Days -13 through Day -11, you will receive palifermin by vein over about 30 seconds each day to help decrease the risk of side effects in the mouth and throat.

You will be admitted on Day -11 and will receive fluids by vein to hydrate you. You will swish the liquids caphosol and glutamine in your mouth 4 times a day, for about 2 minutes each time. You will swish these liquids every day until you leave the hospital. These drugs are also used to help decrease the risk of side effects in the mouth and throat.

On Day -10, you will receive the busulfan test dose by vein over 45 minutes.

On Day -9, you will not receive any drugs.

On Days -8 and -3, you will receive gemcitabine by vein over about 3 hours on both days.

On Days -8 through -5, you will receive busulfan by vein over about 3 hours each day.

Study Drug Administration (for all patients):

On Days -9 through -2, you will receive dexamethasone by vein over about 15 minutes to help decrease the risk of the possible side effects of the study drugs.

On Days -3 and -2, you will receive melphalan by vein over about 30 minutes on both days.

On Day -1, you will not receive any drugs.

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

On Days 0 through 2, you will receive palifermin by vein over about 30 seconds each day.

Beginning on Day 5, you will receive filgrastim (a drug that helps with the growth of white blood cells) through a needle under your skin 1 time each day until your blood cell levels return to normal.

Study Tests:

While you are in the hospital, you will be checked for any side effects as part of your standard of care. Blood (about 2 teaspoons) will be drawn every day to check for side effects.

As part of standard care, you will remain in the hospital for about 3-4 weeks after the transplant. After you are released from the hospital, you must remain in the Houston area to be monitored for infections and other transplant side effects until about Day 30. During this time, you will return to the clinic 1 time each week and the following tests and procedures will be performed:

  • You will be asked about how you are feeling and about any side effects you may be having.
  • Blood (about 2 teaspoons) will be drawn for routine tests.
  • You will have a lung function test about 30-100 days after the transplant.

Length of Study:

You will be followed as part as the study for at least 2 years. You may be taken off study early if the disease gets worse or you experience any intolerable side effects.

At each follow-up visit the following tests and procedures will be performed:

  • Your medical history will be recorded.
  • You will have a physical exam.
  • Blood (about 2 teaspoons) and urine will be collected for routine tests.
  • If your doctor thinks it is needed, you will have a bone marrow biopsy to check the status of the disease.
  • Bone survey: Only once a year.

You must talk to the study doctor if you want to leave the study early. It may be life-threatening to leave the study after you have begun to receive the study drugs but before you receive the stem cells.

This is an investigational study. Busulfan, gemcitabine, and melphalan are all FDA approved and commercially available for the treatment of lymphoma, myeloma, and several other tumors. The use of these study drugs together and the use of gemcitabine at the dose level used in this study is investigational.

Up to 75 patients will take part in this study. All will be enrolled at MD Anderson.

Conditions
Myeloma
Being tested
Palifermin, Dexamethasone, Gemcitabine, Busulfan, Melphalan
Keywords
Autologous Hematopoietic-Cell Support, Stem Cell Transplant, Busulfan, Myleran, Busulfex, Gemcitabine, Gemzar, Melphalan, Alkeran, Decadron, Dexamethasone, G-CSF, Filgrastim, Neupogen
Medical subject headings
Neoplasms, Plasma Cell

What participants receive

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

  • PaliferminDrug

    Also called kepivance

    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.

  • DexamethasoneDrug

    Also called decadron

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

  • GemcitabineDrug

    Also called Gemcitabine Hydrochloride, Gemzar

    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.

  • BusulfanDrug

    Also called myleran, busulfex

    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.

  • MelphalanDrug

    Also called Alkeran

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

  • Stem Cell TransplantProcedure or surgery

    Also called SCT, ASCT

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

  • G-CSFDrug

    Also called Filgrastim, Neupogen

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

Study groups in NCT01237951
Study groupRoleWhat they receive
GemBuMelExperimentalGemcitabine 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.
Receives: Drug: Palifermin; Drug: Dexamethasone; Drug: Gemcitabine; Drug: Busulfan; Drug: Melphalan; Procedure: Stem Cell Transplant; Drug: G-CSF

What is being measured

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

  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.

    Measured: 100 days post-transplant

Secondary outcomes (3)
  1. Progression-free Survival (PFS)

    Number of participants remain free of progression or death after ASCT

    Measured: 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.

  2. Overall Survival

    Number of participants from ASCT to death or last contact

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

  3. Percent of Participants Dying From Treatment-Related Complications

    Participants who died from treatment-related complications from the time of ASCT.

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

Timeline

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

  1. First posted10 Nov 2010 (estimated)
  2. Study start8 Nov 2010
  3. Primary completion20 Sep 2017
  4. Study completion20 Sep 2017

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
75 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01237951
Sponsor's protocol ID
2010-0506
Other IDs
NCI-2012-01906
Status last verified
Apr 2020
First submitted
8 Nov 2010
Last updated
5 May 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 28522110

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Palifermin, Dexamethasone and Gemcitabine in people with Myeloma, run by M.D. Anderson Cancer Center 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 8 inclusion and 7 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: finished, as of the sponsor's last update on 5 May 2020. 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 5 May 2020). 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?

Participants Who Had Measurable Disease at Time of Transplant and Achieved a Stringent Complete Remission (time frame: 100 days post-transplant). 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 NCT01237951, which also lists 1 linked publication.

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 May 2020.

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