A Study of Aplidin (Plitidepsin) 3 h iv in Subjects With Relapsing or Refractory Multiple Myeloma

A Phase 2 study testing Plitidepsin in people with Multiple Myeloma, run by PharmaMar at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

This is a phase II study to determine the efficacy following treatment with Aplidin® 5 mg/m2, given as a 3 hours intravenous infusion every 2 weeks, in patients with relapsed or refractory multiple myeloma (MM). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Multiple Myeloma
What is being tested?: Plitidepsin
Type of treatment: Injection or infusion
How many people: 51 participants
Where: 1 siteUnited States
Study dates: Feb 2005to Aug 2008
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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Written informed consent obtained from the patient before starting any study-specific procedure. If any patient is unable to give consent, it may be obtained from the patient's legal representative if in accordance with local laws and regulations
Age ≥ 18 years
Performance status Eastern Cooperative Oncology Group (ECOG) ≤ 2
Life expectancy ≥ 3 months.
Patient was previously diagnosed with MM based on standard criteria and currently requires treatment because MM relapses following a response to standard chemotherapy or high-dose chemotherapy, or MM is refractory (i.e., failure to achieve at least complete response (CR), partial response (PR) or stable disease (SD)) to their most recent chemotherapy.
Patient has measurable disease, defined as follows:

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For secretory multiple myeloma, measurable disease is defined as any quantifiable serum monoclonal protein value and, where applicable, urine light-chain excretion of ≥ 200 mg/24 hours.
For oligo or non-secretory multiple myeloma, measurable disease is defined by the presence of soft tissue (not bone) plasmacytomas as determined by clinical examination or applicable radiographs (i.e. Magnetic resonance imaging (MRI), Computerized Axial Tomography (CT-Scan)).
Recovery from any non-hematological toxicity derived from previous treatments. The presence of alopecia and National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade < 2 sensitive peripheral neuropathy is allowed.
Patient has the following laboratory values within 14 days before day 1, cycle 1:
Platelet count ≥ 50 x109/L, hemoglobin ≥ 8.0 g/dl and absolute neutrophil count (ANC) ≥ 1.0x109/L; lower values may be accepted if clearly are due to bone marrow involvement by multiple myeloma.
Corrected serum calcium < 14mg/dL.
Aspartate transaminase (AST): ≤ 2.5 x the upper limit of normal.
Alanine transaminase (ALT): ≤ 2.5 x the upper limit of normal.
Total bilirubin: ≤ 1.5 x the upper limit of normal.
Calculated Creatinine clearance: ≥ 40 mL/minute (by means of Crockoft and Gault´s formula).
Left ventricular ejection fraction within normal limits.

Who cannot join

Prior therapy with Aplidin®.
Pregnant or lactating women; men and women of reproductive potential who are not using effective contraceptive methods (double barrier method, intrauterine device, oral contraception)
History of another neoplastic disease. The exceptions are:
non-melanoma skin cancer,
carcinoma in situ of uterine cervix,
any other cancer curatively treated and no evidence of disease for at least 10 years.

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Other relevant diseases or adverse clinical conditions:
History or presence of unstable angina, myocardial infarction, valvular heart disease or congestive heart failure.
Previous mediastinal radiotherapy.
Uncontrolled arterial hypertension despite optimal medical therapy.
Previous treatment with doxorubicin at cumulative doses in excess of 400 mg/m².
Symptomatic arrhythmia or any arrhythmia requiring treatment.
History of significant neurological or psychiatric disorders
Active infection
Patient is known to be human immunodeficiency virus (HIV) positive, Hepatitis B surface antigen-positive or active hepatitis C infection.
Myopathy or any clinical situation that causes significant and persistent elevation of creatine kinase (CK)(>2.5 ULN in two different determinations performed with one week apart)
Significant non-neoplastic liver disease (e.g. cirrhosis, active chronic hepatitis)
Uncontrolled endocrine diseases (e.g. diabetes mellitus, hypothyroidism or hyperthyroidism) (i.e. requiring relevant changes in medication within the last month, or hospital admission within the last 3 months)
Limitation of the patient's ability to comply with the treatment or follow-up protocol.
Treatment with any investigational product in the 30 days period before inclusion in the study or radiotherapy in the 4 weeks before inclusion in the study. Other previous treatments should have been completed 3 weeks before inclusion in the study, and in case of high dose chemotherapy, 8 weeks.
Known hypersensitivity to Aplidin®, mannitol, cremophor, or ethanol or dexamethasone.

Trial locations and contacts

1 site in 1 country.

United States1 site

Jerome Lipper Multiple Myeloma Center - Dept of Medical Oncology - Dana Farber Cancer Institute
Boston, Massachusetts, 02115

Other trials in United States

About this study

Official title: "Phase II Multicenter, Open-Label, Clinical and Pharmacokinetic Study of Aplidin® As A 3-Hour Infusion Every 2 Weeks Alone or in Combination With Dexamethasone, in Pre-Treated Patients With Relapsing or Refractory Multiple Myeloma."

Read the detailed description

This is a phase II study to determine the efficacy following treatment with Aplidin® 5 mg/m2, given as a 3 h iv infusion every 2 weeks, in patients with relapsed or refractory multiple myeloma (MM) and to obtain the following :

Additional pharmacokinetic information for Aplidin® given as 3-hour IV infusion every 2 weeks in patients with MM.
To obtain additional genomic and pharmacodynamics information on MM and Aplidin.
To assess the safety and tolerability of Aplidin® given as 3-hour IV infusion every 2 weeks in patients with MM alone or in combination with dexamethasone given orally as a 20 mg daily for 4 days
To determine the response rate in the second cohort of patients following treatment with Aplidin®, given as a 3 hour infusion every 2 weeks, plus dexamethasone given orally as a 20 mg daily for 4 days, starting the same day of Aplidin® administration, as a second treatment stage in patients with suboptimal response to Aplidin® as single agent (progressive disease after three cycles or stable disease after four cycles).

Conditions: Multiple Myeloma
Being tested: Plitidepsin
Keywords: Myeloma, Aplidin, Plitidepsin, PharmaMar
Medical subject headings: Multiple Myeloma, Neoplasms, Plasma Cell

What participants receive

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

PlitidepsinDrug
3-hour infusion every 2 weeks alone or in combination with dexamethasone

What is being measured

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

Objective Response Rate (ORR), Defined as the Combined Rate of Complete Response, Partial Response and Minimal Response
Complete response(CR):0 percentage the original monoclonal protein level from blood and urine Partial response(PR): ≥50 percentage reduction in the level of serum monoclonal protein Minimal response(MR):≥25 percentage to ≤ 49 percentage reduction in the level of serum monoclonal protein Stable disease: Not meeting the criteria for MR or PD. Progressive disease: >25 percentage increase in level of serum monoclonal paraprotein, which must also be an absolute increase of at least 5 g/L and confirmed on a repeat investigation.
Treatmen failure: Reappearance of serum or urinary paraprotein
Measured: Every 2 weeks until progression or death occurs.

Secondary outcomes (3)

Time to Progression (TTP)
Time to Progression (TTP):date of first infusion to the date of documented progressive disease which can be defined as >25 percentage increase in level of serum monoclonal paraprotein.
Measured: Every 2 weeks until progression or death due to progression occurs. Median TTP and TTP rates at 3 months and 6 months were assessed.
Progression Free Survival (PFS)
Progression Free Survival (PFS): time from the date of first infusion to the date of documented progression or death
Measured: Every 2 weeks until progression or death occurs. Median PFS and PFS rates at 3 months and 6 months were assessed.
Number of Patients With Overall Survival (OS)
Overall Survival (OS): time from the date of first infusion to the date of documented death
Measured: Start of treatment to death. At each patient visit while on treatment, then every 3m during follow-up. Median OS and OS rates at 6 months and 12 months were assessed.

Timeline

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

Feb 2005Aug 2008

First posted29 Sep 2005 (estimated)
Study startFeb 2005
Primary completionAug 2008
Study completionAug 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Multiple MyelomaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 51 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00229203
Sponsor's protocol ID: APL-B-014-03
Status last verified: Dec 2009
First submitted: 27 Sep 2005
Last updated: 24 Dec 2009
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
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Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
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Active, not recruitingPhase 3
A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)
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Active, not recruitingPhase 1/2
A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment
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Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
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All Multiple Myeloma trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Dec 2009. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: "Phase II Multicenter, Open-Label, Clinical and Pharmacokinetic Study of Aplidin® As A 3-Hour Infusion Every 2 Weeks Alone or in Combination With Dexamethasone, in Pre-Treated Patients With Relapsing or Refractory Multiple Myeloma."
ClinicalTrials.gov ID: NCT00229203
Acronym / sponsor ID: APL-B-014-03
Conditions: Multiple Myeloma
Keywords: Myeloma, Aplidin, Plitidepsin, PharmaMar
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 51 participants (actual)
Lead sponsor: PharmaMarIndustry (pharma, biotech, devices)
Study start: Feb 2005
Primary completion: Aug 2008 (actual)
Study completion: Aug 2008 (actual)
First posted: 29 Sep 2005 (estimated)
Results: Posted 14 Dec 2009

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Additional pharmacokinetic information for Aplidin® given as 3-hour IV infusion every 2 weeks in patients with MM.
To obtain additional genomic and pharmacodynamics information on MM and Aplidin.
To assess the safety and tolerability of Aplidin® given as 3-hour IV infusion every 2 weeks in patients with MM alone or in combination with dexamethasone given orally as a 20 mg daily for 4 days
To determine the response rate in the second cohort of patients following treatment with Aplidin®, given as a 3 hour infusion every 2 weeks, plus dexamethasone given orally as a 20 mg daily for 4 days, starting the same day of Aplidin® administration, as a second treatment stage in patients with suboptimal response to Aplidin® as single agent (progressive disease after three cycles or stable disease after four cycles).

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (17 listed)

Written informed consent obtained from the patient before starting any study-specific procedure. If any patient is unable to give consent, it may be obtained from the patient's legal representative if in accordance with local laws and regulations
Age ≥ 18 years
Performance status Eastern Cooperative Oncology Group (ECOG) ≤ 2
Life expectancy ≥ 3 months.
Patient was previously diagnosed with MM based on standard criteria and currently requires treatment because MM relapses following a response to standard chemotherapy or high-dose chemotherapy, or MM is refractory (i.e., failure to achieve at least complete response (CR), partial response (PR) or stable disease (SD)) to their most recent chemotherapy.

Key exclusion criteria (21 listed)

Prior therapy with Aplidin®.
Pregnant or lactating women; men and women of reproductive potential who are not using effective contraceptive methods (double barrier method, intrauterine device, oral contraception)
History of another neoplastic disease. The exceptions are:
Other relevant diseases or adverse clinical conditions:
Limitation of the patient's ability to comply with the treatment or follow-up protocol.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Plitidepsin3-hour infusion every 2 weeks alone or in combination with dexamethasone	Drug	–

Primary outcome

Objective Response Rate (ORR), Defined as the Combined Rate of Complete Response, Partial Response and Minimal Response
Time frame: Every 2 weeks until progression or death occurs.
Complete response(CR):0 percentage the original monoclonal protein level from blood and urine Partial response(PR): ≥50 percentage reduction in the level of serum monoclonal protein Minimal response(MR):≥25 percentage to ≤ 49 percentage reduction in the level of serum monoclonal protein Stable disease: Not meeting the criteria for MR or PD. Progressive disease: >25 percentage increase in level of serum monoclonal paraprotein, which must also be an absolute increase of at least 5 g/L and confirmed on a repeat investigation. Treatmen failure: Reappearance of serum or urinary paraprotein

3 secondary outcomes

Time to Progression (TTP)
Time frame: Every 2 weeks until progression or death due to progression occurs. Median TTP and TTP rates at 3 months and 6 months were assessed.
Progression Free Survival (PFS)
Time frame: Every 2 weeks until progression or death occurs. Median PFS and PFS rates at 3 months and 6 months were assessed.
Number of Patients With Overall Survival (OS)
Time frame: Start of treatment to death. At each patient visit while on treatment, then every 3m during follow-up. Median OS and OS rates at 6 months and 12 months were assessed.

Results and safety

Results posted to the registry on 14 Dec 2009, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Plitidepsin	32	0
Plitidepsin + Dexamethasone	19	0

Primary outcome: Objective Response Rate (ORR), Defined as the Combined Rate of Complete Response, Partial Response and Minimal Response

Time frame: Every 2 weeks until progression or death occurs.. Number. Unit: percentage patients

Measure	Plitidepsin n = 29	Plitidepsin + Dexamethasone n = 18
Complete response	0	0
Partial response	3	11
Minimal response	7	11
Stable Disease/No changes	41	61
Progressive Disease/Treatment failure	48	17

Population analysed: Per protocol - Only 29 of 32 and 18 of 19 enrolled patients were evaluable (analyzed patients)

3 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Plitidepsin	32 of 51 (62.7%)	51 of 51 (100%)	Not reported
Plitidepsin + Dexamethasone	11 of 19 (57.9%)	19 of 19 (100%)	Not reported

Limitations and caveats (from the sponsor): 32 patients were treated with plitidepsin as single agent;afterwards 19 of them were treated with plitidepsin+dexamethasone combination.Therefore 32+19=51 is the no. patients at risk for plitidepsin and 19 is no. of patients at risk for dexamethasone

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2009.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Multiple Myeloma

Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Active, not recruitingPhase 3
A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)
Multiple Myeloma
Active, not recruitingPhase 1/2
A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment
Multiple Myeloma
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Paul Richardson, MD study chair

Chief division hematological malignancies - Medical Oncology - Dana Farber Cancer Institute - Harvard Medical School, Boston

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Plitidepsin in people with Multiple Myeloma, run by PharmaMar 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 17 inclusion and 21 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 24 Dec 2009. 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 14 Dec 2009). 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?

Objective Response Rate (ORR), Defined as the Combined Rate of Complete Response, Partial Response and Minimal Response (time frame: Every 2 weeks until progression or death occurs.). 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 NCT00229203.

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 24 Dec 2009.