NCT00743288 · REGISTRY CONDITION SEARCH

Melphalan and Panobinostat (LBH589) for the Treatment of Patients With Recurrent Multiple Myeloma

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1, PHASE2
Status at capture: COMPLETED
Registry last update: 2014-05-08

RATIONALE: Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Panobinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving melphalan together with panobinostat may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of melphalan when given together with panobinostat in treating patients with recurrent multiple myeloma.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

Duration of Response

→

outcome · POSTED

Time to Progression

→

outcome · POSTED

Maximum Tolerated Dose (MTD)

→

outcome · POSTED

MTD

→

outcome · POSTED

Overall Response Rate (ORR) and Clinical Benefit Rate (CBR) [ORR= Complete Response (CR) + Very Good Partial Response (VGPR) + Partial Response (PR)]; CBR=ORR + Minimal Response (MR)] Following Treatment With Panobinostat and Melphalan

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→

Who could take part

eligibility Criteria: Inclusion criteria: * Diagnosis of multiple myeloma, based on the following criteria: * Major criteria * Plasmacytomas on tissue biopsy (1) * Bone marrow plasmacytosis (\> 30% plasma cells) (2) * Monoclonal immunoglobulin (Ig) spike on serum electrophoresis, IgG \> 3.5 g/dL or IgA \> 2.0 g/dL, and kappa or lambda light chain excretion \> 1 g/day on 24-hour urine protein electrophoresis (3) * Minor Criteria * Bone marrow plasmacytosis (10-30% plasma cells) (a) * Monoclonal immunoglobulin present but of lesser magnitude than given under major criteria (b) * Lytic bone lesions ©) * Normal IgM \< 50 mg/dL, IgA \< 100 mg/dL, or IgG \< 600 mg/dL (d) * Meets any of the following sets of multiple myeloma diagnostic criteria: * Any two of the major criteria * Major criterion 1 plus minor criterion b, c, or d * Major criterion 3 plus minor criterion a or c * Minor criteria a, b, and c, OR a, b, and d * Measurable disease, defined as a monoclonal immunoglobulin spike on serum electrophoresis of ≥ 1 g/dL and/or urine monoclonal immunoglobulin spike of ≥ 200 mg/24 hours, or evidence of lytic bone disease * Must have received ≥ 1 prior treatment regimen OR refractory to most recent chemotherapy * Relapsed following stabilization or response to standard first-line chemotherapy (e.g., vincristine, doxorubicin hydrochloride, and prednisone or melphalan and prednisone) or first-line high-dose chemotherapy * Refractory (i.e., failure to achieve at least complete or partial response or stable disease) to most recent chemotherapy, whether or not containing systemic corticosteroids * Prior treatment with ≤ 4 days of a total of 400 mg of prednisone (or an equivalent potency of another steroid) for myeloma is not considered a regimen * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 * Life expectancy \> 3 months * Platelet count ≥ 75 x 10\^9/L (≥ 50 x 10\^9/L if bone marrow is extensively infiltrated) * Absolute neutrophil count ≥ 1.5 x 10\^9/L (≥ 1.0 x 10\^9/L if bone marrow is extensively infiltrated) * Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤ 2.5 times upper limit of normal (ULN) * Serum bilirubin ≤ 1.5 times ULN * Creatinine clearance ≥ 30 mL/min; creatinine \> 10 mL/min and \< 30 mL/min due to significant myelomatous involvement of the kidneys allowed with medical director approval * Serum potassium ≥ lower limit of normal (LLN) * Serum magnesium ≥ LLN * Serum phosphorus ≥ LLN * Prior localized radiotherapy Exclusion criteria: * Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS syndrome) * Plasma cell leukemia * Pregnant or nursing females; fertile patients must use effective contraception * Peripheral neuropathy \> grade 2 * Impaired cardiac function or clinically significant cardiac disease (including congenital long QT syndrome, history or presence of sustained ventricular tachyarrhythmia; history of ventricular fibrillation or Torsade de Pointes; bradycardia, defined as heart rate (HR) \< 50 beats per minute (bpm) \[pacemaker allowed provided HR ≥ 50 bpm\]; corrected QT interval \> 450 msec on screening ECG; left ventricular ejection fraction below normal on screening ECHO or multigated acquisition (MUGA) scan; right bundle branch block with left anterior hemiblock (bifascicular block); myocardial infarction or unstable angina within the past 6 months; New York Heart Association class III-IV congestive heart failure; uncontrolled hypertension; history of labile hypertension; history of poor compliance with an antihypertensive regimen) * Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat * Prior malignancy within the past 5 years except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix * Other concurrent severe and/or uncontrolled medical or psychiatric conditions (e.g., uncontrolled diabetes or active or uncontrolled infection), including abnormal laboratory values that could cause unacceptable safety risks or compromise protocol compliance * Known positivity for HIV or hepatitis B or C * Severe hypercalcemia (i.e., serum calcium ≥ 14 mg/dL) * Significant history of non-compliance to medical regimens or unwillingness or inability to comply with instructions given by the study staff * Concurrent medication that risk prolonging the QT interval or inducing Torsades de Pointes * Prior panobinostat * Received chemotherapy, bortezomib, thalidomide, lenalidomide or arsenic trioxide within 3 wks of enrollment (with the exception of nitrosoureas within 6 wks of enrollment) * Received corticosteroids (\>10 mg/day prednisone or equivalent) within three weeks before enrollment. * Received immunotherapy within \< 8 weeks; antibody within \< 4 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.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Schedule A: 10mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 of a 28-day cycle and melphalan PO at 0.05 mg/kg on days 1-5 of week 1. Toxicity led to the following changes in dose and schedule Schedule B1: 10mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1. Schedule B2: 20mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 and 0.05 mg/kg melphalan POon days 1, 3 and 5 of week 1. Schedule C: 20mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1 and 2 and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1 Schedule D1: 15 mg/daily LBH589 PO and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1. Schedule D2: 15 mg/daily LBH589 PO and 0.10 mg/kg melphalan PO on days 1, 3 and 5 of week 1. Schedule D3: 20 mg/daily LBH589 PO and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1.
intervention Names
Drug: Melphalan
Drug: Panobinostat
label
Melphalan and Panobinostat
type
EXPERIMENTAL

interventions

arm Group Labels
Melphalan and Panobinostat
description
Same as above
name
Melphalan
other Names
Phenylalanine mustard, Alkeran
type
DRUG
arm Group Labels
Melphalan and Panobinostat
name
Panobinostat
other Names
LBH589
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 40
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Phase 1: to determine the MTD of panobinostat (LBH589) in combination with melphalan to be used in the Phase 2 portion of the study
measure
Maximum Tolerated Dose (MTD)
time Frame
12 months
description
Phase 1: to determine MTD of melphalan in combination with panobinostat to be used in the Phase 2 portion of the study
measure
MTD
time Frame
12 months
description
Responses were evaluated according to criteria modified from those developed by Blade et al., 1998 The reference point for evaluating response improvement is the baseline. This baseline reference point is also valid when a patient has already achieved a response and transitions through into a better response grade.
measure
Overall Response Rate (ORR) and Clinical Benefit Rate (CBR) [ORR= Complete Response (CR) + Very Good Partial Response (VGPR) + Partial Response (PR)]; CBR=ORR + Minimal Response (MR)] Following Treatment With Panobinostat and Melphalan
time Frame
24 months

secondary Outcomes

measure
Duration of Response
time Frame
First evidence of PR or better (for overall response) and MR or better (for clinical benefit response) to start of disease progression or death
measure
Time to Progression
time Frame
Time from the start of treatment to progressive disease

Full study description

brief Summary: RATIONALE: Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Panobinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving melphalan together with panobinostat may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of melphalan when given together with panobinostat in treating patients with recurrent multiple myeloma.
detailed Description: OBJECTIVES: Primary * To establish the maximum tolerated dose (MTD) and determine the dose-limiting toxicities (DLT) of panobinostat in combination with melphalan in patients with relapsed or refractory multiple myeloma. (Phase I) * To determine the dose of this regimen to be used in the Phase II portion of the study. (Phase I) * To determine the efficacy as evidenced by the response rate (combined complete response, very good partial response, partial response, and minimal response) in patients treated with this regimen. (Phase II) Secondary * To obtain preliminary evidence of efficacy of the combination of LBH589 and melphalan for patients with relapsed or refractory multiple myeloma. (Phase I) * To determine the safety and tolerability of this regimen in these patients. (Phase II) * To determine time to disease progression, time to response, and duration of response in patients treated with this regimen. (Phase II) * To determine progression-free survival and overall survival of patients treated with this regimen. (Phase II) OUTLINE: This is a multicenter, phase I, dose-escalation study followed by a phase II study. Patients receive oral panobinostat once daily on days 1, 3, 5, 8, 10, and 12 and oral melphalan once daily on days 1, 3 and 5. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Source references

references

citation
Berenson JR, Hilger JD, Yellin O, Boccia RV, Matous J, Dressler K, Ghazal HH, Jamshed S, Kingsley EC, Harb WA, Noga SJ, Nassir Y, Swift RA, Vescio R. A phase 1/2 study of oral panobinostat combined with melphalan for patients with relapsed or refractory multiple myeloma. Ann Hematol. 2014 Jan;93(1):89-98. doi: 10.1007/s00277-013-1910-2. Epub 2013 Oct 18.
pmid
24135804
type
RESULT

Source notices and limitations

Discovery and provenance

release id
ctgov-registry-1336d216cbd1bbff780dac70
edge id
nct-edge-8839a1334ceedc0743b4
requested nct id
NCT00743288
primary nct id
NCT00743288
source kind
ctgov_condition_query
source url
https://clinicaltrials.gov/api/v2/studies?query.cond=Plasma+Cell+Neoplasms&filter.advanced=AREA%5BHasResults%5Dtrue&pageSize=1000&format=json&countTotal=true
source record id
Source null
source file sha256
2314ce01316b2d7044d298c6d25eda12e99cc5f44273bc75efed6cd5e03a8c14
payload sha256
aeb4d9a52e760af2300d7f93fcc64c6d8234aa1d2b01be5c2b2c7f905f9140d3
payload
clinical indication matching status
condition_index_match_asserted_by_registry_not_reviewed
end exclusive
true
id
nct-edge-8839a1334ceedc0743b4
link basis
returned_by_explicit_condition_and_posted_results_filter_query
nct id
NCT00743288
occurrences
context exact
NCT00743288
end
11
exact text
NCT00743288
start
0
offset unit
unicode_code_points
query cond
Plasma Cell Neoplasms
query disease state id
ds-plasma-cell-neoplasms
source file
/Users/arunverma/Documents/ChatGPT/Cancer Statistics Website/research-data/2026-09-10/clinicaltrials-condition/round-0000/raw/cond-plasma-cell-neoplasms-000.json
source file sha256
2314ce01316b2d7044d298c6d25eda12e99cc5f44273bc75efed6cd5e03a8c14
source json pointer
/studies/280/protocolSection/identificationModule/nctId
source kind
ctgov_condition_query
source record id
Source null
source string basis
parsed_JSON_string_unmodified
source string sha256
dbc884b9f8e50f39c83aebed154e2f58ef6fadc792851bdba1e0b566d0ca7036
source url
https://clinicaltrials.gov/api/v2/studies?query.cond=Plasma+Cell+Neoplasms&filter.advanced=AREA%5BHasResults%5Dtrue&pageSize=1000&format=json&countTotal=true

Preserved source evidence · Not medical advice