Panobinostat Combined With High-Dose Gemcitabine/Busulfan/Melphalan With Autologous Stem Cell Transplant for Patients With Refractory/Relapsed Myeloma - Full Text View

Purpose

The goal of this clinical research study is to learn if a combination of panobinostat, gemcitabine, busulfan, and melphalan and a stem cell transplant can help to control MM. The safety of this combination will also be studied.

Condition	Intervention	Phase
Multiple Myeloma	Drug: Busulfan Drug: Palifermin Drug: Panobinostat Drug: Gemcitabine Drug: Melphalan Drug: Dexamethasone acetate Drug: Caphosol Drug: Glutamine Drug: Pyridoxine Procedure: Stem Cell Transplant	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: No masking Primary Purpose: Treatment
Official Title:	Panobinostat Combined With High-Dose Gemcitabine/Busulfan/Melphalan With Autologous Stem Cell Transplant for Patients With Refractory/Relapsed Myeloma

Resource links provided by NLM:

Genetics Home Reference related topics: multiple myeloma

MedlinePlus related topics: Multiple Myeloma

Drug Information available for: Busulfan Melphalan Melphalan hydrochloride Gemcitabine Gemcitabine hydrochloride Panobinostat

Genetic and Rare Diseases Information Center resources: Multiple Myeloma

U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

Improvement in Progression-Free Survival (PFS) in Participants with Refractory Multiple Myeloma Receiving First Stem Cell Transplant [ Time Frame: 1 year ]
The 1-year PFS rate in cohort 1 (refractory, 1st transplant) associated with GemBuMel is 62%. With 40 patients in this cohort, assuming exponentially-distributed PFS times, 1.5 years of accrual followed by 2 years of follow-up, and a one-sided 5% Type I error rate, 40 patients provides more than 80% power to detect an increase in one-year PFS to 75% in this cohort.

International Myeloma Working Group (IMWG) uniform response criteria used.
Improvement in Progression-Free Survival (PFS) in Participants with Relapsed Multiple Myeloma Receiving Second Salvage Stem Cell Transplant [ Time Frame: 1 year ]
In cohort 2 (2nd transplant), the historical 1-year PFS rate is 55%. Under the same assumptions, 40 patients will provide more than 80% power to detect an increase in 1-year PFS to 69%.

International Myeloma Working Group (IMWG) uniform response criteria used.


Estimated Enrollment:	80
Actual Study Start Date:	September 2015
Estimated Study Completion Date:	September 2018
Estimated Primary Completion Date:	September 2018 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Refractory Disease - First Stem Cell Transplant Group Low test dose Busulfan by vein as an outpatient or inpatient. If outpatient test dose Busulfan by vein before hospital admission, then on Days -8 through -5. If inpatient, test dose Busulfan by vein on Day -10, then on Days -8 through -5. Palifermin by vein on Days -12, through -10 if outpatient, and on Days -14 through -12 if inpatient, and on Day 0, +1 and +2 for both groups. Participants swish liquids Caphosol and Glutamine in their mouth 4 times a day beginning on Day -9. Dexamethasone by vein 2 times a day on Days -9 through Day -2. Panobinostat by mouth 1 time a day on Days -8 through Day -2. Gemcitabine by vein on Day -8 and - 3. Melphalan given by vein on Day-3 and -2. Pyridoxine by vein or mouth three times a day from Day -1. Stem cell transplant procedure on Day 0.	Drug: Busulfan Busulfan 32 mg/m2 by vein Test Dose before admission if outpatient, and Day -10 if inpatient. Busulfan AUC 4,000 by vein on Days -8 to -5. Other Names: Busulfex Myleran Drug: Palifermin 60 microgram/kg by vein on Days -12, -11, -10, 0, +1 and +2, or -14, -13, -12, 0,+1 and +2. Other Name: Kepivance Drug: Panobinostat Panobinostat 20 mg by mouth on Days -9 to -2. Other Name: LBH589B Drug: Gemcitabine Gemcitabine 1,875 mg/m2 by vein on Days -8 and -3. Other Names: Gemcitabine Hydrochloride Gemzar Drug: Melphalan Melphalan 60 mg/m2 by vein on Days -3 and -2. Other Name: Alkeran Drug: Dexamethasone acetate Dexamethasone 8 mg by vein 2 times a day on Days -9 through Day -2. Other Name: Decadron Drug: Caphosol Caphosol oral rinses 30 mL four times a day from day -9 until discharge. Drug: Glutamine Glutamine 15 g four times a day, swished, gargled and spit started on day -9 until discharge. Other Names: Enterex Glutapak-10 NutreStore Resource GlutaSolve Sympt-X G.I. Sympt-X Drug: Pyridoxine Pyridoxine 100 mg by vein or mouth three times a day from Day -1. Procedure: Stem Cell Transplant Stem cell transplant performed on Day 0.
Experimental: Relapsed Disease - Second Salvage Stem Cell Transplant Group Low test dose Busulfan by vein as an outpatient or inpatient. If outpatient test dose Busulfan by vein before hospital admission, then on Days -8 through -5. If inpatient, test dose Busulfan by vein on Day -10, then on Days -8 through -5. Palifermin by vein on Days -12, through -10 if outpatient, and on Days -14 through -12 if inpatient, and on Day 0, +1 and +2 for both groups. Participants swish liquids Caphosol and Glutamine in their mouth 4 times a day beginning on Day -9. Dexamethasone by vein 2 times a day on Days -9 through Day -2. Panobinostat by mouth 1 time a day on Days -8 through Day -2. Gemcitabine by vein on Day -8 and - 3. Melphalan given by vein on Day-3 and -2. Pyridoxine by vein or mouth three times a day from Day -1. Stem cell transplant procedure on Day 0.	Drug: Busulfan Busulfan 32 mg/m2 by vein Test Dose before admission if outpatient, and Day -10 if inpatient. Busulfan AUC 4,000 by vein on Days -8 to -5. Other Names: Busulfex Myleran Drug: Palifermin 60 microgram/kg by vein on Days -12, -11, -10, 0, +1 and +2, or -14, -13, -12, 0,+1 and +2. Other Name: Kepivance Drug: Panobinostat Panobinostat 20 mg by mouth on Days -9 to -2. Other Name: LBH589B Drug: Gemcitabine Gemcitabine 1,875 mg/m2 by vein on Days -8 and -3. Other Names: Gemcitabine Hydrochloride Gemzar Drug: Melphalan Melphalan 60 mg/m2 by vein on Days -3 and -2. Other Name: Alkeran Drug: Dexamethasone acetate Dexamethasone 8 mg by vein 2 times a day on Days -9 through Day -2. Other Name: Decadron Drug: Caphosol Caphosol oral rinses 30 mL four times a day from day -9 until discharge. Drug: Glutamine Glutamine 15 g four times a day, swished, gargled and spit started on day -9 until discharge. Other Names: Enterex Glutapak-10 NutreStore Resource GlutaSolve Sympt-X G.I. Sympt-X Drug: Pyridoxine Pyridoxine 100 mg by vein or mouth three times a day from Day -1. Procedure: Stem Cell Transplant Stem cell transplant performed on Day 0.

Arms

Assigned Interventions

Experimental: Refractory Disease - First Stem Cell Transplant Group

Low test dose Busulfan by vein as an outpatient or inpatient. If outpatient test dose Busulfan by vein before hospital admission, then on Days -8 through -5. If inpatient, test dose Busulfan by vein on Day -10, then on Days -8 through -5. Palifermin by vein on Days -12, through -10 if outpatient, and on Days -14 through -12 if inpatient, and on Day 0, +1 and +2 for both groups. Participants swish liquids Caphosol and Glutamine in their mouth 4 times a day beginning on Day -9. Dexamethasone by vein 2 times a day on Days -9 through Day -2. Panobinostat by mouth 1 time a day on Days -8 through Day -2. Gemcitabine by vein on Day -8 and - 3. Melphalan given by vein on Day-3 and -2. Pyridoxine by vein or mouth three times a day from Day -1. Stem cell transplant procedure on Day 0.

Drug: Busulfan

Busulfan 32 mg/m2 by vein Test Dose before admission if outpatient, and Day -10 if inpatient. Busulfan AUC 4,000 by vein on Days -8 to -5.

Other Names:

Busulfex
Myleran

Drug: Palifermin

60 microgram/kg by vein on Days -12, -11, -10, 0, +1 and +2, or -14, -13, -12, 0,+1 and +2.

Other Name: Kepivance

Drug: Panobinostat

Panobinostat 20 mg by mouth on Days -9 to -2.

Other Name: LBH589B

Drug: Gemcitabine

Gemcitabine 1,875 mg/m2 by vein on Days -8 and -3.

Other Names:

Gemcitabine Hydrochloride
Gemzar

Drug: Melphalan

Melphalan 60 mg/m2 by vein on Days -3 and -2.

Other Name: Alkeran

Drug: Dexamethasone acetate

Dexamethasone 8 mg by vein 2 times a day on Days -9 through Day -2.

Other Name: Decadron

Drug: Caphosol

Caphosol oral rinses 30 mL four times a day from day -9 until discharge.

Drug: Glutamine

Glutamine 15 g four times a day, swished, gargled and spit started on day -9 until discharge.

Other Names:

Enterex
Glutapak-10
NutreStore
Resource
GlutaSolve
Sympt-X G.I.
Sympt-X

Drug: Pyridoxine

Pyridoxine 100 mg by vein or mouth three times a day from Day -1.

Procedure: Stem Cell Transplant

Stem cell transplant performed on Day 0.

Experimental: Relapsed Disease - Second Salvage Stem Cell Transplant Group

Low test dose Busulfan by vein as an outpatient or inpatient. If outpatient test dose Busulfan by vein before hospital admission, then on Days -8 through -5. If inpatient, test dose Busulfan by vein on Day -10, then on Days -8 through -5. Palifermin by vein on Days -12, through -10 if outpatient, and on Days -14 through -12 if inpatient, and on Day 0, +1 and +2 for both groups. Participants swish liquids Caphosol and Glutamine in their mouth 4 times a day beginning on Day -9. Dexamethasone by vein 2 times a day on Days -9 through Day -2. Panobinostat by mouth 1 time a day on Days -8 through Day -2. Gemcitabine by vein on Day -8 and - 3. Melphalan given by vein on Day-3 and -2. Pyridoxine by vein or mouth three times a day from Day -1. Stem cell transplant procedure on Day 0.

Drug: Busulfan

Busulfan 32 mg/m2 by vein Test Dose before admission if outpatient, and Day -10 if inpatient. Busulfan AUC 4,000 by vein on Days -8 to -5.

Other Names:

Busulfex
Myleran

Drug: Palifermin

60 microgram/kg by vein on Days -12, -11, -10, 0, +1 and +2, or -14, -13, -12, 0,+1 and +2.

Other Name: Kepivance

Drug: Panobinostat

Panobinostat 20 mg by mouth on Days -9 to -2.

Other Name: LBH589B

Drug: Gemcitabine

Gemcitabine 1,875 mg/m2 by vein on Days -8 and -3.

Other Names:

Gemcitabine Hydrochloride
Gemzar

Drug: Melphalan

Melphalan 60 mg/m2 by vein on Days -3 and -2.

Other Name: Alkeran

Drug: Dexamethasone acetate

Dexamethasone 8 mg by vein 2 times a day on Days -9 through Day -2.

Other Name: Decadron

Drug: Caphosol

Caphosol oral rinses 30 mL four times a day from day -9 until discharge.

Drug: Glutamine

Glutamine 15 g four times a day, swished, gargled and spit started on day -9 until discharge.

Other Names:

Enterex
Glutapak-10
NutreStore
Resource
GlutaSolve
Sympt-X G.I.
Sympt-X

Drug: Pyridoxine

Pyridoxine 100 mg by vein or mouth three times a day from Day -1.

Procedure: Stem Cell Transplant

Stem cell transplant performed on Day 0.

Show Detailed Description

Eligibility


Ages Eligible for Study:	18 Years to 65 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age 18 to 65 years.
Refractory or relapsed myeloma, defined as one or more of the following: 2.1. Treated with first-line therapy including at least 2 cycles of lenalidomide, bortezomib or thalidomide, and one or more of the following: 2.1.1. Less than PR to first-line therapy. 2.1.2. Relapse after 1st line therapy. 2.2. High-risk cytogenetics, defined by del(13q) by conventional cytogenetics, or by del(17p), t(4;14), t(14;16), t(14;20) or 1q+ by FISH. 2.3. Relapse after a prior ASCT. 2.4. Plasma cell leukemia. 2.5. Soft tissue plasmacytoma.
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 SGOT and/or 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 FEV1, FVC and 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-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 CD34+ cells/kg previously apheresed.
Ability to provide written informed consent.

Exclusion Criteria:

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 (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.
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 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: 11.1. History or presence of sustained ventricular tachyarrhythmia. (Patients with a history of atrial arrhythmia are eligible but should be discussed with Novartis prior to enrollment). 11.2 Any history of ventricular fibrillation or torsade de pointes. 11.3. Bradycardia defined as HR< 50 bpm. Patients with pacemakers are eligible if HR >/= 50 bpm. 11.4. Screening ECG with a QTc > 470 msec. 11.5. Right bundle branch block + left anterior hemiblock (bifascicular block). 11.6. Myocardial infarction or unstable angina </= 12 months prior to starting study drug. 11.7. Other clinically significant heart disease (e.g., CHF 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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02506959

Contacts


Contact: Yago Nieto, MD, PHD	713-792-8750

Locations


United States, Texas
University of Texas MD Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Novartis Pharmaceuticals

Investigators


Principal Investigator:	Yago Nieto, MD, PHD	M.D. Anderson Cancer Center

More Information

Additional Information:

University of Texas MD Anderson Cancer Center Website This link exits the ClinicalTrials.gov site


Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT02506959 History of Changes
Other Study ID Numbers:	2014-0516 NCI-2015-01308 ( Registry Identifier: NCI CTRP )
Study First Received:	July 22, 2015
Last Updated:	June 16, 2017


Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by M.D. Anderson Cancer Center:


Multiple myeloma (MM) MM Refractory Relapsed Stem Cell Transplant Busulfan Busulfex Myleran Palifermin Kepivance Panobinostat LBH589B Gemcitabine Gemcitabine Hydrochloride	Gemzar Melphalan Alkeran Dexamethasone Decadron Pyridoxine Caphosol Glutamine Enterex Glutapak NutreStore Resource GlutaSolve Sympt-X

Additional relevant MeSH terms:


Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases Gemcitabine	BB 1101 Panobinostat Melphalan Busulfan Dexamethasone Dexamethasone acetate Dexamethasone 21-phosphate Pyridoxine Pyridoxal Vitamin B 6 Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Antiviral Agents

ClinicalTrials.gov processed this record on July 14, 2017