Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Antineoplastic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Doxorubicin

Liposomal doxorubicin

Dexamethasone

Bortezomib

Dexamethasone acetate

PAD induction Open Label Treatment: Four 21-day Treatment Cycles Bortezomib 1.3 mg/m2 i.v. (D1 4 8 \& 11) Doxorubicin 20 mg/m2 i.v. (D1 \& 4) Dexamethasone 20 mg p.o. (D1 2 4 5 8 9 11 \& 12)

Open Label Treatment:

Four 21-day Treatment Cycles Bortezomib 1.3 mg/m2 i.v. (D1, 4, 8 \& 11), Doxorubicin 20 mg/m2 i.v. (D1 \& 4), Dexamethasone 20 mg p.o. (D1, 2, 4, 5, 8 , 9, 11 \& 12)

PAD induction

Janssen-Cilag Pty Ltd Clinical Trial

The purpose of this study is to determine efficacy of treatment with bortezomib (in combination with doxorubicin and dexamethasone) in previously untreated patients with Multiple Myeloma.

This is an open-label, single-arm, multicentre study which will enroll approximately 105 patients. Open-label means all people involved in the study know the identity of the intervention. Single-arm means there is one group of patients, all receiving the same treatment. Four 21-day cycles of a combination of bortezomib i.v. (intravenous) 1.3 mg/m2 (Days 1, 4, 8 and 11), doxorubicin i.v. 20 mg/m2 (days 1 and 4) and dexamethasone p.o. (by mouth) (days 1, 2, 4, 5, 8, 9, 11 and 12) (PAD) will be given. Patients will be discontinued if disease progresses, or unacceptable treatment-related toxicity occurs. Following PAD treatment, patients will have peripheral blood stem cells (PBSC) collected, and an autologous stem cell transplant (ASCT) will be performed. Patients will then make monthly visits to the Study Doctor until 1 year after start of treatment, and attend a final follow-up visit at 2 years. Efficacy assessment of response to PAD will be made using the International Myeloma Working Group (IMWG) criteria. The primary outcome is to compare the overall response rate following 4 cycles of PAD induction therapy between patients with and without extra copies of the long arm of the first chromosome (1q21) measured by fluorescent in situ hybridisation (FISH) in their marrow at baseline. Patient reported outcomes will be assessed using the AQoL (Assessment of Quality of Life). Safety will be evaluated throughout the study by assessment of adverse events including changes in physical examination, concomitant medication, ECOG (Eastern Cooperative Oncology Group) scores, vital signs and clinical laboratory findings. A sample size of 105 provides 80% power (a=0.05) to detect a difference in overall response rate of 28% at the end of 4 cycles of PAD. This is based on the assumptions that 44% of patients have amplification of 1q21 1, 2, the overall response rate with PAD combination therapy is 80%; the overall response rate with PAD if PAD therapy does not overcome 1q21 amplification is assumed to be 64%, while without 1q21 amplification it is assumed to be 92%. That is: Overall Response Rate (ORR) = P1q21 amplified x ORRamplified + P1q21 not amplified x ORRnot amplified i.e. 80% = 44% x 64% + 56% x 92%. The sample size of 105 allows for a 20% drop-out rate. Four 21-day cycles of PAD: a combination of bortezomib i.v. (intravenous) 1.3 mg/m2 (Days 1, 4, 8 and 11), doxorubicin i.v. 20 mg/m2 (days 1 and 4) and dexamethasone p.o. (by mouth) (days 1, 2, 4, 5, 8, 9, 11 and 12).

A Study of Efficacy of Treatment With Bortezomib (in Combination With Doxorubicin and Dexamethasone) in Previously Untreated Patients With Multiple Myeloma

A Phase II Trial of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction Therapy in Patients With Untreated Multiple Myeloma (MM), Stratified for Markers of Bortezomib Resistance

International Myeloma Working Group (IMWG) criteria - CR: negative immunofixation on the serum and urine, no soft tissue plasmacytomas and \<5% plasma cells in the bone marrow; sCR: CR+normal free light chain ratio, no clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR: serum and urine M-protein detected by immunofixation but not electrophoresis, \>90% in serum M-protein+urine, M-protein level \<100 mg/24hour; PR: ≥50% decrease of serum and M-protein, 24 hour urinary M-protein decrease by ≥90% or \<200 mg/24hour

Number of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR) and stable disease (SD).

Responders are the number of participants who achieved stringent complete response (sCR)/ complete response (CR), very good partial response (VGPR) or partial response (PR) following PAD induction.

Number of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), stable disease (SD) and relapse as per IMWG criteria.

Percentage of participants who did not have any of the following events: Death, Disease progression, Relapse, Cardiovascular accidents, Deep vein thrombosis, Pulmonary embolism, Fracture, Acute renal failure, Nervous system disorders 2 years after Day 1 Cycle 1 of bortezomib, doxorubicin and dexamethasone (PAD).

Percentage of participants who had no event of death 2 years after Day 1 Cycle 1 of bortezomib, doxorubicin and dexamethasone (PAD).

The AQoL is a multi-attribute utility health-related quality of life (HRQoL) instrument. It combines the 4 dimensions of independent living, relationships, senses and mental health into a single utility score. The AQoL instrument scores between 1 (best HRQoL) and -0.04 (worst possible HRQoL).

Number of participants who are responders and nonresponders after 4 cycles of bortezomib, doxorubicin and dexamethasone (PAD) induction stratified by protein expression (p53).

Number of participants who are responders and nonresponders after 4 cycles of bortezomib, doxorubicin and dexamethasone (PAD) induction stratified by protein expression (Cyclin D1).

Number of participants who are responders and nonresponders after 4 cycles of bortezomib, doxorubicin and dexamethasone (PAD) induction stratified by protein expression (bcl-2)

Number of participants who are responders and nonresponders after 4 cycles of bortezomib, doxorubicin and dexamethasone (PAD) induction stratified by protein expression (FGFR3)

Percentage of participants who had no event of death 2 years after Day 1 Cycle 1 of bortezomib, doxorubicin and dexamethasone (PAD) stratified by protein expression (p53).

Percentage of participants who had no event of death 2 years after Day 1 Cycle 1 of bortezomib, doxorubicin and dexamethasone (PAD) stratified by protein expression (Cyclin D1).

Percentage of participants who had no event of death 2 years after Day 1 Cycle 1 of bortezomib, doxorubicin and dexamethasone (PAD) stratified by protein expression (bcl-2).

Percentage of participants who had no event of death 2 years after Day 1 Cycle 1 of bortezomib, doxorubicin and dexamethasone (PAD) stratified by protein expression (FGFR3).

Janssen-Cilag Pty Ltd

Participants with 1q21 amplification. Four 21-day cycles of bortezomib 1.3 mg/m2 intravenous (IV) on Days 1, 4, 8 and 11; plus doxorubicin 20 mg/m2 IV on Days 1 and 4; and dexamethasone 20 mg oral on Days 1, 2, 4, 5, 8, 9, 11 and 12.

1q21 Amplified

Participants without 1q21 amplification. Four 21-day cycles of bortezomib 1.3 mg/m2 intravenous (IV) on Days 1, 4, 8 and 11; plus doxorubicin 20 mg/m2 IV on Days 1 and 4; and dexamethasone 20 mg oral on Days 1, 2, 4, 5, 8, 9, 11 and 12.

1q21 Not Amplified

Participants who failed 1q21 test/had missing results for 1q21 test. Four 21-day cycles of bortezomib 1.3 mg/m2 intravenous (IV) on Days 1, 4, 8 and 11; plus doxorubicin 20 mg/m2 IV on Days 1 and 4; and dexamethasone 20 mg oral on Days 1, 2, 4, 5, 8, 9, 11 and 12.

Failed/Missing Test

Four 21-day cycles of bortezomib 1.3 mg/m2 intravenous (IV) on Days 1, 4, 8 and 11; plus doxorubicin 20 mg/m2 IV on Days 1 and 4; and dexamethasone 20 mg oral on Days 1, 2, 4, 5, 8, 9, 11 and 12.

Total

Age, Continuous

Sex: Female, Male

White

Asian

Mauritian

Indian

Middle Eastern

South American

Appears White

Missing race

Race/Ethnicity, Customized

Regional Medical Affairs Director Asia Pacific

Null Hypothesis: There is no difference in response rate between 1q21 amplified and 1q21 NOT amplified

Non Responder

Responder

Intent-to-treat (ITT) population- All enrolled participants who proceeded to receive Day 1 of Cycle 1 of PAD induction.

Overall Response Rate (ORR): Number of Participants Who Are Responders (Had Stringent Complete Response [sCR], CR, Very Good Partial Response [VGPR] or Partial Response [PR]) After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction

stringent complete response (sCR)

complete response (CR)

Very Good Partial Response (VGPR)

Partial Response (PR)

Stable Disease (SD)

Failed/Missing

Intent-to-treat (ITT) population - All participants who were screened and received at least one dose of PAD

Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction

Overall Response Rate (ORR) to Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction 3-months Following Autologous Stem Cell Transplant (ASCT).

Relapse

Disease Response 3-months After Autologous Stem Cell Transplant (ASCT)

Event Free Survival (EFS)

Overall Survival

Assessment of Quality of Life (AQoL) Scores

p53 Non Responder

p53 Responder

Negative

Positive

Intent-to-treat (ITT) population - All participants who were screened and received at least one dose of PAD. The ORR was imputed, with those who discontinued treatment or who had efficacy data unavailable being coded as Non-Responders.

Overall Response Rate (ORR) Stratified by Protein Expression (p53)

Cyclin D1 Non Responder

Cyclin D1 Responder

Participants without Cyclin D1 expression

Overall Response Rate (ORR) Stratified by Protein Expression (Cyclin D1).

bcl-2 Non Responder

bcl-2 Responder

Overall Response Rate (ORR) Stratified by Protein Expression (Bcl-2)

FGFR3 Non Responder

FGFR3 Responder

Overall Response Rate (ORR) Stratified by Protein Expression (FGFR3)

Intent-to-treat (ITT) population - All participants who were screened and received at least one dose of PAD. The OS was not imputed.

Overall Survival (OS) Stratified by Protein Expression (p53).

Overall Survival (OS) Stratified by Protein Expression (Cyclin D1)

Overall Survival (OS) Stratified by Protein Expression (Bcl-2)

Overall Survival (OS) Stratified by Protein Expression (FGFR3)

Completed PAD Induction

Primary Endpoint Analysis

Completed 3-month Follow up

Secondary Endpoint Analysis

Lenalidomide

BB 1101

Panobinostat

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Histone Deacetylase Inhibitors

Enzyme Inhibitors

Combination Therapy: Panobinostat, Carfilzomib, Lenalidomide, Dexamethasone (Ca-R-Pa-Diem) . Participants will receive up to 8 cycles of the combination as induction after which will proceed with consolidation therapy with transplant as per institutional standards. After transplant, participants receive maintenance with panobinostat/lenalidomide. The maintenance dose and schedule of panobinostat will be same given during induction for 1 year. The maintenance dose of lenalidomide will be 10 mg given for 21 days of 28 days cycle until disease progression.

Induction Phase: Panobinostat (dose escalation beginning at 10 mg) will be administered 3 times a week (TIW) by mouth every other week starting on day 1 of each cycle.

Maintenance Phase: Panobinostat will be administered TIW by mouth every other week starting on day 1 of each cycle. The dose of panobinostat during maintenance phase will be the same dose taken during cyce 8 of induction phase.

Induction Phase: Carfilzomib will be administered at 20 mg/m\^2 on Cycle 1 Day 1. Beginning on Cycle 1 Day 2 the carfilzomib dose will be according to the assigned level of 27 mg/m\^2 or 36 mg/m\^2. Carfilzomib will be administered twice weekly IV on Days 1,2, 8,9,15, and 16.

Carfilzomib

Induction Phase: Lenalidomide (25 mg) will be administered once-daily by mouth on Days 1-21, 25.

Maintenance Phase: Lenalidomide (10 mg) will be administered once-daily by mouth on days 1-21.

Induction Phase: Dexamethasone (20 mg) will be administered twice weekly by mouth or by IV on Days 1,2, 8, 9, 15, and 16.

Melissa Alsina, M.D.

The purpose of this study for Phase l is to determine the maximum tolerated dose of panobinostat given in combination with carfilzomib, lenalidomide, and dexamethasone in 28-day cycles as induction (initial) therapy to participants with newly diagnosed multiple myeloma.

In Phase ll, investigators will evaluate the safety (side effects) and efficacy (effectiveness) of panobinostat in combination with carfilzomib, lenalidomide, and dexamethasone.

Induction Therapy for Multiple Myeloma With Carfilzomib, Lenalidomide,Dexamethasone,Panobinostat

Phase I-II Study of Carfilzomib, Lenalidomide, Dexamethasone, and Panobinostat, Ca-R-Pa-Diem, as Induction Therapy for Newly Diagnosed, Untreated, Transplant-Eligible, Multiple Myeloma Patients

MTD of the Ca-R-Pa-Diem given in combination to newly diagnosed Multiple Myeloma patients.

Response rates by International Myeloma Working Group Uniform Response Criteria (IMWG-URC). Complete Response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow. sCR: CR plus normal free light chain (FLC) ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence.

Overall response rate will be the proportion of participants who achieved Stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), or Partial Response (PR). Response rate determined by IMWG-URC will be calculated based on the number of participants with each of response categories (sCR, CR, VGPR, PR, and progressive disease) at each treatment cycle.

Novartis

Amgen

H. Lee Moffitt Cancer Center and Research Institute

Induction Starting Doses: Lenalidomide 25 mg orally daily on days 1-14; Bortezomib 1.3 mg/m\^2 intravenous (IV) daily on days 1, 4, 8 and 11; Dexamethasone 20 mg orally daily on days 1, 2, 4, 5, 8, 9, 11, 12 and Panobinostat orally 10 mg on days 1, 3, 5, 8, 10 and 12. Induction therapy consists of 21 day cycle in Part A and 28 day cycle in Part B.

Symptom Questionnaire completed on day 1 of each cycle.

Induction Therapy (Part A, 21-day cycles): 10 mg by mouth on Days 1, 3, 5, 8, 10, and 12 for 2 weeks with 1 week of rest at the end of each cycle.

Induction Therapy (Part B, 28-day cycles): 10 mg by mouth on Days 1, 3, 5, 15, 17, and 19 of every cycle.

Maintenance dose (Part A, 28-day cycles): Maximum tolerated dose (MTD) from Induction phase on Days 1, 3, 5, 8, 10, and 12 of each cycle.

Maintenance dose (Part B, 28-day cycles): Maximum tolerated dose (MTD) from Induction phase on Days 1, 3, 5, 15, 17, 19 of each cycle.

Induction Therapy (Part A, 21-day cycles): 1.3 mg/m\^2 by vein daily on days 1, 4, 8 and 11 of Cycles 1 - 8.

Induction Therapy (Part B, 28-day cycles): 1.3 mg/m\^2 by vein daily on days 1, 8 and 15 of Cycles 1 - 8.

Induction Therapy (Part A, 21-day cycles): 25 mg by mouth daily on days 1-14 of every cycle.

Induction Therapy (Part B, 28-day cycles): 25 mg by mouth daily on days 1-21 of every cycle.

Maintenance dose (Parts A and B, 28-day cycles): Last tolerated dose from Induction Phase on Days 1 - 21 of each cycle.

Induction Therapy (Part A, 21-day cycles): 20 mg by mouth daily on Days 1, 2, 4, 5, 8, 9, 11 and 12 of Cycles 1 - 8.

Induction Therapy (Part B, 28-day cycles): 20 mg by mouth daily on Days 1, 2, 8, 9, 15 and 16 of Cycles 1-8.

Maintenance dose (Parts A and B, 28-day cycles): Last tolerated dose from Induction Phase on Days 1, 8, 15, 21 of each cycle.

Symptom Questionnaire

Elisabet E. Manasanch, MD

The goal of this clinical research study is to find the highest tolerable dose of the drug panobinostat that can be given in combination with the drugs Velcade (bortezomib), Revlimid (lenalidomide), and Decadron (dexamethasone) to patients with MM. The safety of this drug combination will also be studied.

Panobinostat is designed to cause chemical changes in different groups of proteins that are attached to DNA (the genetic material of cells), which may slow the growth of cancer cells or cause the cancer cells to die.

Bortezomib is designed to block a protein that causes cells to grow. This may cause cancer cells to die.

Lenalidomide is designed to change the body's immune system. It may also interfere with the development of tiny blood vessels that help support tumor growth. This may slow the growth of cancer cells.

Dexamethasone is a corticosteroid that is similar to a natural hormone made by your body. Dexamethasone is often given to MM patients in combination with other chemotherapy to treat cancer.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a dose level of panobinostat based on when you join this study.

If you are enrolled in the first portion of Part A, up to 4 dose levels of panobinostat will be tested. Three (3) to 6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of panobinostat is found.

If you are enrolled in the second portion of Part A, you will receive panobinostat at the recommended dose from the first portion of Part A.

If you are enrolled in the first portion of Part B, up to 3 dose levels of panobinostat will be tested. Three (3) to 6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of panobinostat is found.

If you are enrolled in the second portion of Part B, you will receive panobinostat at the recommended dose from the first portion of Part B.

Study Drug Administration:

Induction Therapy (Part A):

In the Induction phase of therapy, each cycle is 21 days.

On Days 1, 4, 8, and 11 of Cycles 1-8, you will receive bortezomib either through a needle under your skin or by vein over 3-5 seconds. You will be watched by the study staff for 30 minutes after the infusion.

On Days 1-14 of every cycle, you will take lenalidomide by mouth 1 time each day. You should swallow the lenalidomide capsules whole with 1 cup (about 8 ounces) of water. Do not break, chew, or open the capsules.

You will take panobinostat by mouth 1 time a day with food on Days 1, 3, 5, 8, 10 and 12 for 2 weeks with 1 week of rest at the end of each cycle.

On Days 1, 2, 4, 5, 8, 9, 11, and 12 of Cycles 1-8, you will take dexamethasone by mouth 1 time a day. After 8 cycles, you may continue to take dexamethasone if the doctor thinks it is needed. Dexamethasone should be taken with food.

Induction Therapy (Part B):

In Part B, the induction phase of therapy is 28-day cycles.

On Days 1, 8, and 15 of Cycles 1-8, you will receive bortezomib either through a needle under your skin or by vein over 3-5 seconds. You will be watched by the study staff for 30 minutes after the infusion.

On Days 1-21 of every cycle, you will take lenalidomide by mouth 1 time each day. You should swallow the lenalidomide capsules whole with 1 cup (about 8 ounces) of water. Do not break, chew, or open the capsules.

You will take panobinostat by mouth 1 time a day with food on Days 1, 3, 5, 15, 17, 19 of every cycle.

On Days 1, 2, 8, 9, 15,16, Cycles 1-8, you will take dexamethasone by mouth 1 time a day. After 8 cycles, you may continue to take dexamethasone if the doctor thinks it is needed. Dexamethasone should be taken with food.

Maintenance Therapy (Parts A and B):

In the Maintenance phase of therapy, each cycle is 28 days.

You will take lenalidomide by mouth 1 time each day on Days 1-21 of each cycle.

You will take dexamethasone by mouth 1 time a day on Days 1, 8, 15, and 21 of each cycle.

In Part A, you will take panobinostat by mouth 1 time a day on Days 1, 3, 5, 8, 10, and 12 of each cycle. In Part B, you will take panobinostat by mouth 1 time a day on Days 1, 3, 5, 15, 17, 19 of each cycle.

Other Instructions:

You can take the study drugs anytime during the day but you should take them at the same time every day.

If you miss a dose of lenalidomide, take it as soon as you remember on the same day. If you miss taking your dose for the entire day, take your regular dose the next scheduled day (do NOT take double your regular dose to make up for the missed dose). If you take more than the prescribed dose of lenalidomide, you should seek emergency medical care if needed and contact the study staff right away.

Your study drug doses may be lowered if you have side effects.

You will be given a drug diary for each cycle to write in to help keep track of your study drug doses. You should bring the drug diary and pill bottles to your study visit at the beginning of each new cycle.

The panobinostat capsule(s) should be swallowed with 1 cup of water. You should try to take the dose at around the same time each day. If you vomit after taking panobinostat, you should not take it again until your next scheduled dose. If you forget to take a dose in the morning, you can take it up to 12 hours later. If you miss a dose for more than 12 hours, you should wait until your next scheduled dose. Do not make up missed doses.

On Day 1 of every new study cycle and Cycle 1, Day 5, you should wait to take your panobinostat until you come to the clinic for study tests. Some of the Day 1 tests need to be performed before dosing.

You need to follow all panobinostat dosing instructions as written. Do not miss any panobinostat capsules. You will be asked to return all unused study drug in the bottles provided, along with empty bottles, on Day 1 of every cycle, starting with Cycle 2. Capsules should not be transferred between bottles at any time. Please do not allow anyone else to handle or touch the study drug.

You can stop anytime after Cycle 4 of Induction to have a stem cell transplant. If you decide with your doctor to delay the transplant, you will still be recommended to have your stem cells collected. You will continue with Induction therapy until you have had 4-8 cycles. After that, you will receive Maintenance therapy.

You will be given other drugs to help prevent side effects. The study staff will tell you about these drugs, how they will be given, and the possible risks.

Study Visits (Part A):

On Day 1 of each cycle:

* You will have a physical exam, including measurement of your vital signs.
* Blood (about 5 tablespoons) will be drawn for routine tests and biomarker testing.
* Blood (about 1 teaspoon) and/or urine will be collected to check the status of the disease. If urine is collected, you will collect the urine over 24 hours. This urine or blood will also be used for a pregnancy test if you are able to become pregnant.
* You will complete the symptom questionnaire.
* You will be asked about any symptoms you may have had and any drugs you may be taking.
* If the doctor thinks it is needed, you will have bone x-rays, an MRI and/or a CT scan to check the status of the disease.

On Days 1 and 5 of Cycle 1, you will have 3 ECGs before the study drug dose and 3 ECGs after the dose.

On Day 1 of Cycles 2-8, you will have 3 ECGs.

On Days 4, 8, and 11 of Cycles 1-8:

°Blood (about 4 tablespoons) will be drawn for routine tests.

At the end of Cycle 8 (or if you are going to have a stem cell transplant, at the end of Cycle 4):

* You will have a physical exam, including measurement of your vital signs.
* You will be asked about any symptoms you may have had and any other drugs you may be taking.
* Blood (about 2 tablespoons) will be collected for routine tests.
* Blood (about 1 teaspoon) and/or urine will be collected to check the status of the disease. If urine is collected, you will be asked to collect your urine over 24 hours.
* You will have bone x-rays to check the status of the disease.
* If the disease completely responds to the study drugs, you will have a bone marrow aspiration and/or biopsy to confirm the response.

On Day 1 of Maintenance Therapy, or Cycles 9 and beyond (if you choose to delay stem cell transplant) :

* You will have a physical exam, including measurement of your vital signs.
* You will be asked about any symptoms you may have had and any other drugs you may be taking.
* You will complete the symptom questionnaire.
* Blood (about 4 tablespoons) will be drawn for routine tests and biomarker testing.
* Blood (about 1 teaspoon) and/or urine will be collected to check the status of the disease. If urine is collected, you will collect the urine for 24 hours. This urine or blood will also be used for a pregnancy test if you are able to become pregnant.
* If the doctor thinks it is needed, you will have bone x-rays, an MRI and/or a CT scan to check the status of the disease.

Study Visits (Part B):

On Days 8 and 15 of Cycle 1, blood (about 2 teaspoons) will be drawn for routine tests.

On Day 1 of Cycles 2 and beyond:

* You will have a physical exam, including measurement of your vital signs.
* You will be asked about any symptoms you may have had and any other drugs you may be taking.
* Blood (about 2 teaspoons) and urine will be collected for routine tests.
* You will have 3 ECGs.

Pregnancy Tests (Parts A and B):

During induction therapy, if you are a woman who is able to become pregnant and you have regular or no periods, you will have a blood (about 1 tablespoon) or urine pregnancy test weekly for the first 21 days and then every 21 days while on therapy (including breaks in therapy). If you are a woman who is able to become pregnant and your cycles are irregular, you will have a blood (about 1 tablespoon) or urine pregnancy test weekly for the first 21 days during then every 11-14 days while on therapy (including breaks in therapy).

During maintenance therapy, if you are a woman who is able to become pregnant and have regular or no menstruation, you must have a pregnancy test every 28 days while on therapy (including breaks in therapy). If you are a woman who is able to become pregnant and your cycles are irregular, you will have a blood (about 1 tablespoon) or urine pregnancy test every 14 days (+/-1 day) and every 28 days.

Length of Treatment:

You may receive induction therapy for up to 8 cycles, followed by maintenance therapy for an additional 2 years. You will no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over once you have completed the end-of-treatment and follow-up visits.

End-of-Treatment Visit:

Within 30 days after your last dose of study drugs:

* You will have a physical exam, including measurement of your vital signs.
* You will be asked about any symptoms you may be experiencing.
* Blood (about 4 tablespoon) and urine will be collected for routine tests.
* Blood (about 1 teaspoon) and/or urine will be collected to check the status of the disease. If urine is collected, you will collect the urine for 24 hours.
* If the disease completely responds to the study drugs, you will have a bone marrow aspiration and/or biopsy to confirm the response.
* If the doctor thinks it is needed, you will have an MRI and/or a CT scan to check the status of the disease.
* If you are able to become pregnant, you will have a urine or blood (about 1 tablespoon) pregnancy test.

Follow-Up:

Every 3 months (+/-1 month) for the first 2 years after the stem cell transplant and then every 6 months (+/- 2 months) for Years 3 and 4, the following tests and procedures will be performed:

* You will have a physical exam.
* Blood (about 4 tablespoons) and urine will be collected for routine tests.
* If the doctor thinks it is needed, you will also have an MRI and/or a CT scan, x-rays, and/or a bone marrow aspiration and biopsy.

Every 6 months during the first 2 years after you are finished with maintenance therapy, you will be asked how you are doing. This will be done at the clinic or by a phone call from the study staff. If you are called, the calls should take 5-10 minutes.

If the disease gets worse, you will no longer have follow-up.

This is an investigational study. Panobinostat is not FDA approved or commercially available. It is currently being used for research purposes only. Bortezomib is FDA approved and commercially available for the treatment of MM. Lenalidomide is FDA approved and commercially available for the treatment of certain types of myelodysplastic syndrome and for MM. The use of this drug combination to treat MM is investigational.

Up to 54 patients will take part in this study. All will be enrolled at MD Anderson.

Combination Therapy of Lenalidomide/Bortezomib/Dexamethasone and Panobinostat in Transplant Eligible New Diagnosed Multiple Myeloma (MM) Patients

Phase I/Ib Trial of the Efficacy and Safety of Combination Therapy of Lenalidomide/Bortezomib/Dexamethasone and Panobinostat in Transplant Eligible Patients With Newly Diagnosed Multiple Myeloma (MM)

Maximum tolerated dose (MTD) defined as highest dose level in which 6 participants have less than 2 instances of dose limiting toxicities (DLT). Toxicities graded in severity according to guidelines outlined in NCI-CTCAE version 4.0. Hematologic and non-hematologic DLTs defined differently, and will be based on experiences that occur during the first cycle of study drug administration.

Response assessed according to the recently published International Uniform Response Criteria for multiple myeloma established by the International Myeloma Working Group (IMWG; Durie et al 2006).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Efficacy of Treatment With Bortezomib (in Combination With Doxorubicin and Dexamethasone) in Previously Untreated Patients With Multiple Myeloma	NCT00872521	Multiple Myelom...	PAD induction	18 Years -	Janssen-Cilag Pty Ltd
Induction Therapy for Multiple Myeloma With Carfilzomib, Lenalidomide,Dexamethasone,Panobinostat	NCT02802163	Multiple Myelom...	Panobinostat Carfilzomib Lenalidomide Dexamethasone	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Induction Therapy for Multiple Myeloma With Carfilzomib, Lenalidomide,Dexamethasone,Panobinostat	NCT02802163	Multiple Myelom...	Panobinostat Carfilzomib Lenalidomide Dexamethasone	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Combination Therapy of Lenalidomide/Bortezomib/Dexamethasone and Panobinostat in Transplant Eligible New Diagnosed Multiple Myeloma (MM) Patients	NCT01440582	Myeloma	Panobinostat Bortezomib Lenalidomide Dexamethasone Symptom Questio...	18 Years -	M.D. Anderson Cancer Center

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