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Plasma Cell LeukemiaPhase 2NCT02506959

Panobinostat, Gemcitabine Hydrochloride, Busulfan, and Melphalan Before Stem Cell Transplant in Treating Patients With Refractory or Relapsed Multiple Myeloma

A Phase 2 study testing Autologous Hematopoietic Stem Cell Transplantation, Busulfan and Gemcitabine Hydrochloride in people with Plasma Cell Leukemia and Plasmacytoma, 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

This phase II trial studies how well panobinostat, gemcitabine hydrochloride, busulfan, and melphalan before stem cell transplant work in treating patients with multiple myeloma that does not respond to treatment (refractory) or has returned (relapsed). Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Autologous Hematopoietic Stem Cell Transplantation, Busulfan and Gemcitabine Hydrochloride
Could I receive a placebo?
No, everyone receives an active treatment
How many people
83 participants
Where
1 siteUnited States
Study dates
14 Sep 2015to 3 Jun 2024
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 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Refractory or relapsed myeloma, defined as one or more of the following:
  • Treated with first-line therapy including at least 2 cycles of lenalidomide, bortezomib or thalidomide, and one or more of the following:
  • Less than partial response (PR) to first-line therapy
  • Relapse after first (1st) line therapy
  • High-risk cytogenetics, defined by deletion (del)(13q) by conventional cytogenetics, or by del(17p), t(4;14), t(14;16), t(14;20) or 1q+ by fluorescence in situ hybridization (FISH)
  • Relapse after a prior autologous stem cell transplant (ASCT)
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  • Plasma cell leukemia
  • Soft tissue plasmacytoma
  • Serum creatinine =< 1.8 mg/dL and/or estimated serum creatinine clearance >= 50 ml/min
  • Serum glutamic oxaloacetic transaminase (SGOT) and/or serum glutamate pyruvate transaminase (SGPT) =< 3 x upper limit of normal
  • Serum bilirubin =< 2 x upper limit of normal, unless proven to be due to disease involvement
  • Alkaline phosphatase =< 2 x upper limit of normal, unless proven to be due to disease involvement
  • Adequate pulmonary function with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and diffusion capacity of the 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
  • Clinically euthyroid; note: patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism
  • Zubrod performance status < 2
  • Negative beta-human chorionic gonadotropin (HCG) test in a woman of child-bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization
  • Availability of >= 2.5 million cluster of differentiation (CD)34+ cells/kg previously apheresed
  • Ability to provide written informed consent

Who cannot join

  • Prior whole brain irradiation
  • Having received radiation therapy to head and neck (excluding eyes), and internal organs of chest, abdomen or pelvis in the month prior to enrollment
  • Active hepatitis B, either active carrier (hepatitis B surface antigen positive [HBsAg +]) or viremic (hepatitis B virus [HBV] deoxyribonucleic acid [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
  • Known positivity for human immunodeficiency virus (HIV)
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  • Autologous stem-cell transplant in the previous six months
  • Needing valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat
  • Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes or active or uncontrolled infection) including abnormal laboratory values, that could cause unacceptable safety risks or compromise compliance with the protocol
  • Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:
  • History or presence of sustained ventricular tachyarrhythmia; (patients with a history of atrial arrhythmia are eligible but should be discussed with Secura Bio, Inc (Secura Bio) prior to enrollment)
  • Any history of ventricular fibrillation or torsade de pointes
  • Bradycardia defined as heart rate (HR) < 50 beats per minute (bpm); patients with pacemakers are eligible if HR >= 50 bpm
  • Screening electrocardiogram (ECG) with a corrected QT (QTc) > 470 msec
  • Right bundle branch block + left anterior hemiblock (bifascicular block)
  • Myocardial infarction or unstable angina =< 12 months prior to starting study drug
  • Other clinically significant heart disease (e.g., congestive heart failure [CHF] New York [NY] Heart Association class III or IV , uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
  • Have undergone major surgery =< 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  • Prior malignancy with in the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix)
  • Any significant history of non-compliance to medical regimens or unwilling or unable to comply with the instructions given to him/her by the study staff
  • Received targeted agents within 2 weeks or within 5 half-lives of the agent and active metabolites (whichever is longer) and who have not recovered from side effects of those therapies
  • Having received immunotherapy or chemotherapy within 2 weeks; or radiation therapy to > 30% of marrow-bearing bone within =< 2 weeks prior to starting study treatment; or who have not yet recovered from side effects of such therapies
  • Grade >= 3 nonhematological toxicity from prior therapy that has not resolved to =< grade 1

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Panobinostat Combined With High-Dose Gemcitabine/Busulfan/Melphalan With Autologous Stem Cell Transplant for Patients With Refractory/Relapsed Myeloma

This phase II trial studies how well panobinostat, gemcitabine hydrochloride, busulfan, and melphalan before stem cell transplant work in treating patients with multiple myeloma that does not respond to treatment (refractory) or has returned (relapsed). Panobinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving high-dose chemotherapy, such as gemcitabine hydrochloride, busulfan, and melphalan, before a peripheral blood stem cell transplant helps kill any cancer cells that are in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. Previously collected stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the progression-free survival (PFS) in patients with refractory or relapsed myeloma receiving panobinostat/gemcitabine hydrochloride (gemcitabine)/busulfan/melphalan (panobinostat/Gem/Bu/Mel) with autologous stem-cell transplant, either as a first or a salvage stem-cell transplant.

SECONDARY OBJECTIVES:

  1. To evaluate the complete response (CR) rate. II. To determine the overall survival (OS). III. To determine the CR + very good partial remission (VGPR) rate. IV. To determine the overall response rate (ORR). V. To determine minimal residual disease posttransplant, measured by multiparametric flow cytometry (MFC).

VI. To describe the toxicity profile of panobinostat/Gem/Bu/Mel. VII. To analyze the predictive value of pretransplant levels in myeloma cells of X-box binding protein 1 (XBP1), inositol-requiring enzyme 1 (IRE1), unspliced XBP1 (XBP1u), sliced XBP1 (XPB1s), XBP1u/XPBs ratio and v-myc myelocytomatosis viral oncogene homolog (avian) (Myc), by analyzing their correlation with CR, VGPR+CR and response rate (RR).

VIII. To study the prognostic effect of pretransplant levels in myeloma cells of XBP1, IRE1, XBP1u, XPB1s, XBP1u/XPBs ratio and Myc, by analyzing their correlation with PFS and OS.

OUTLINE:

Patients receive panobinostat orally (PO) once daily (QD) on days -9 to -2, gemcitabine hydrochloride intravenously (IV) over 4 hours on days -8 and -3, busulfan IV over 3 hours on days -8 to -5, and melphalan IV over 30 minutes on days -3 and -2. Patients then undergo autologous peripheral blood stem cell transplant on day 0.

After completion of study treatment, patients are followed up at 1 month, 100 days, 6 months, 1 year, and then every 3-6 months for at least 2 years.

Being tested
Autologous Hematopoietic Stem Cell Transplantation, Busulfan, Gemcitabine Hydrochloride, Melphalan, Panobinostat
Medical subject headings
Leukemia, Plasma Cell, Plasmacytoma, Multiple Myeloma

What participants receive

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

  • Autologous Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called Autologous Hematopoietic Cell Transplantation

    Undergo autologous peripheral blood stem cell transplant

  • BusulfanDrug

    Also called 1, 4-Bis[methanesulfonoxy]butane, BUS, Bussulfam, Busulfanum

    Given IV

  • Gemcitabine HydrochlorideDrug

    Also called dFdCyd, Difluorodeoxycytidine Hydrochloride, FF 10832, FF-10832

    Given IV

  • MelphalanDrug

    Also called Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard

    Given IV

  • PanobinostatDrug

    Also called Faridak, LBH589

    Given PO

  • Peripheral Blood Stem Cell TransplantationProcedure or surgery

    Also called PBPC transplantation, PBSCT, Peripheral Blood, Peripheral Blood Progenitor Cell Transplantation

    Undergo autologous peripheral blood stem cell transplant

  • Pharmacological StudyOther

    Correlative studies

Study groups in NCT02506959
Study groupRoleWhat they receive
Cohort 1_1st Auto TP Conditioned with panobinostat and Gem/Bu/MelExperimentalPatients receive panobinostat PO QD on days -9 to -2, gemcitabine hydrochloride IV over 4 hours on days -8 and -3, busulfan IV over 3 hours on days -8 to -5, and melphalan IV over 30 minutes on days -3 and -2. Patients then undergo autologous peripheral blood stem cell transplant on day 0.
Receives: Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Busulfan; Drug: Gemcitabine Hydrochloride; Drug: Melphalan; Drug: Panobinostat; Procedure: Peripheral Blood Stem Cell Transplantation; Other: Pharmacological Study
Cohort 2_2nd Auto TP Conditioned with panobinostat and Gem/Bu/MelExperimentalPatients receive panobinostat PO QD on days -9 to -2, gemcitabine hydrochloride IV over 4 hours on days -8 and -3, busulfan IV over 3 hours on days -8 to -5, and melphalan IV over 30 minutes on days -3 and -2. Patients then undergo autologous peripheral blood stem cell transplant on day 0.
Receives: Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Busulfan; Drug: Gemcitabine Hydrochloride; Drug: Melphalan; Drug: Panobinostat; Procedure: Peripheral Blood Stem Cell Transplantation; Other: Pharmacological Study

What is being measured

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

  1. Progression Free Survival (PFS)

    Number of participants alive and disease free one year post auto transplant in patients with refractory or relapsed myeloma receiving panobinostat/gemcitabine/busulfan/melphalan (panobinostat/Gem/Bu/Mel) with autologous stem-cell transplant, either as a first or a salvage stem-cell transplant.

    Measured: 1 year

Secondary outcomes (2)

  1. Overall Survival (OS)

    Number of participants with refractory or relapse Myeloma who still remain alive two years post transplant

    Measured: Up to 2 years

  2. Participants Who Experienced Grade 3 or Higher Adverse Events

    Number of Participants who experienced grade 3 or higher Adverse Events during the first 100 days of the transplant.

    Measured: Up to day 100

Timeline

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

  1. First posted23 Jul 2015 (estimated)
  2. Study start14 Sep 2015
  3. Primary completion3 Jun 2024
  4. Study completion3 Jun 2024

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
83 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02506959
Sponsor's protocol ID
2014-0516
Other IDs
NCI-2015-01308, 2014-0516
Status last verified
Feb 2025
First submitted
22 Jul 2015
Last updated
18 Mar 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Autologous Hematopoietic Stem Cell Transplantation, Busulfan and Gemcitabine Hydrochloride in people with Plasma Cell Leukemia and Plasmacytoma, 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 20 inclusion and 24 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 18 Mar 2025. 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 18 Mar 2025). 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?

Progression Free Survival (PFS) (time frame: 1 year). 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 NCT02506959.

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 18 Mar 2025.

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