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

NCT02506959 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2014-0516NCI-2015-01308
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Plasma Cell Leukemia; Plasmacytoma; Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (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.

  1 year

Secondary Outcomes (2)

• Overall Survival (OS)

  Up to 2 years

• Participants Who Experienced Grade 3 or Higher Adverse Events

  Up to day 100

Study Arms (2)

Cohort 1_1st Auto TP Conditioned with panobinostat and Gem/Bu/Mel

EXPERIMENTAL

Patients 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.

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/Mel

EXPERIMENTAL

Patients 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.

Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Busulfan; Drug: Gemcitabine Hydrochloride; Drug: Melphalan; Drug: Panobinostat; Procedure: Peripheral Blood Stem Cell Transplantation; Other: Pharmacological Study

Interventions

Autologous Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo autologous peripheral blood stem cell transplant

Also known as: Autologous Hematopoietic Cell Transplantation

Cohort 1_1st Auto TP Conditioned with panobinostat and Gem/Bu/Mel; Cohort 2_2nd Auto TP Conditioned with panobinostat and Gem/Bu/Mel

Busulfan DRUG

Given IV

Also known as: 1, 4-Bis[methanesulfonoxy]butane, BUS, Bussulfam, Busulfanum, Busulfex, Busulphan, CB 2041, CB-2041, Glyzophrol, GT 41, GT-41, Joacamine, Methanesulfonic Acid Tetramethylene Ester, Methanesulfonic acid, tetramethylene ester, Mielucin, Misulban, Misulfan, Mitosan, Myeleukon, Myeloleukon, Myelosan, Mylecytan, Myleran, Sulfabutin, Tetramethylene Bis(methanesulfonate), Tetramethylene bis[methanesulfonate], WR-19508

Cohort 1_1st Auto TP Conditioned with panobinostat and Gem/Bu/Mel; Cohort 2_2nd Auto TP Conditioned with panobinostat and Gem/Bu/Mel

Gemcitabine Hydrochloride DRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, FF 10832, FF-10832, FF10832, Gemcitabine HCI, Gemzar, LY-188011, LY188011

Cohort 1_1st Auto TP Conditioned with panobinostat and Gem/Bu/Mel; Cohort 2_2nd Auto TP Conditioned with panobinostat and Gem/Bu/Mel

Melphalan DRUG

Given IV

Also known as: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard, L-Sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalanum, Phenylalanine Mustard, Phenylalanine Nitrogen Mustard, Sarcoclorin, Sarkolysin, WR-19813

Cohort 1_1st Auto TP Conditioned with panobinostat and Gem/Bu/Mel; Cohort 2_2nd Auto TP Conditioned with panobinostat and Gem/Bu/Mel

Panobinostat DRUG

Given PO

Also known as: Faridak, LBH589

Cohort 1_1st Auto TP Conditioned with panobinostat and Gem/Bu/Mel; Cohort 2_2nd Auto TP Conditioned with panobinostat and Gem/Bu/Mel

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo autologous peripheral blood stem cell transplant

Also known as: PBPC transplantation, PBSCT, Peripheral Blood, Peripheral Blood Progenitor Cell Transplantation, PERIPHERAL BLOOD STEM CELL TRANSPLANT, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant, Peripheral Stem Cell Transplantation

Cohort 1_1st Auto TP Conditioned with panobinostat and Gem/Bu/Mel; Cohort 2_2nd Auto TP Conditioned with panobinostat and Gem/Bu/Mel

Pharmacological Study OTHER

Correlative studies

Cohort 1_1st Auto TP Conditioned with panobinostat and Gem/Bu/Mel; Cohort 2_2nd Auto TP Conditioned with panobinostat and Gem/Bu/Mel

Eligibility Criteria

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

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia, Plasma Cell; Plasmacytoma; Multiple Myeloma

Interventions

Busulfan; Gemcitabine; Melphalan; Panobinostat; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Hydroxamic Acids; Hydroxylamines; Amines; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; 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: Yago Nieto, MD / Stem Cell Transplantation Department
• Organization: The University of Texas MD Anderson Cancer Center

ynieto@mdanderosn.org

713-792-8750

Study Officials

• Yago L Nieto

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2015
• First Posted: July 23, 2015
• Study Start: September 14, 2015
• Primary Completion: June 3, 2024
• Study Completion: June 3, 2024
• Last Updated: March 18, 2025
• Results First Posted: March 18, 2025

Record last verified: 2025-02

Locations

US (1)