Refractory Multiple MyelomaPhase 1NCT02998047
A Phase I Study of Lintuzumab-Ac225 in Patients With Refractory Multiple Myeloma
A Phase 1 study testing Lintuzumab AC 225 in people with Refractory Multiple Myeloma, run by Actinium Pharmaceuticals at 5 sites in United States.
Trial summary
1. Establish the MTD of Lintuzumab-Ac225 as monotherapy 2. Establish overall response rate (ORR) where ORR = CR + sCR+ VGPR+PR) 3. Confirm the safety profile of the treatment regimen 4. Estimate progression-free survival (PFS) and overall survival Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Refractory Multiple Myeloma
- What is being tested?
- Lintuzumab AC 225
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 5 sitesUnited States
- Study dates
- Dec 2016to May 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Confirmed diagnosis of multiple myeloma with measurable disease, as defined by the presence of M immunoglobulin protein in serum electrophoresis of at least 0.5 g/dL for IgG or 0.5 g/dL for IgA or urinary excretion of at least 200 mg monoclonal light chain per 24 hours.
- Clinical diagnosis of multiple myeloma requiring treatment that has relapsed after or proven refractory to at least three prior treatment regimens, and in the opinion of the investigator must not be candidates for any FDA approved drug known to provide clinical benefit.
- All acute toxicities from any prior therapy (radiotherapy, chemotherapy, or surgical procedures) resolved to Grade ≤ 2, NCI CTCAE.
- Serum potassium and magnesium levels within institutional normal limits. Total serum calcium or ionized calcium level must be greater than or equal to the lower limit of normal.
- Greater than 25% of myeloma plasmocytes from bone marrow must be CD33 positive.
- Required baseline laboratory data including: White blood cell count, Absolute neutrophil count (ANC), Platelets, Hemoglobin, Serum creatinine, AST, Creatinine clearance, Bilirubin , AST and ALT , FEV1/FVC
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
Who cannot join
- Sex and Reproductive Status
- Women of child bearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least one month (4 weeks) before and for at least six months (6 months) after the last dose of study medication.
- Women who are pregnant or breastfeeding
- Women with a positive pregnancy test on enrollment or prior to investigational product administration.
- Men whose sexual partners are WOCBP, who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least six months (6 months) after completion of study medication.
- Target Disease Exceptions
Show all 32Show fewer
- Concurrent therapy with any other investigational agent.
- Concomitant therapy with bisphosphonates.
- Pathological fracture within 3 months prior to treatment;
- Symptomatic spinal cord compression; .
- Medical History and Concurrent Diseases
- Treatment with chemotherapy or biological therapy 3 weeks prior to enrollment;
- Presence of HAHA on screening
- No bone marrow transplant within 3 months prior to treatment initiation
- Prior treatment with radiation to cumulative maximum tolerated dose
- Clinically significant cardiac disease (NYHA Class III or IV) including preexisting arrhythmia (such as ventricular tachycardia, ventricular fibrillation, or "Torsade de Pointes")
- Myocardial infarction, uncontrolled angina within 6 months, congestive heart failure, or cardiomyopathy.
- Abnormal QTc interval prolonged (> 450 msec) after electrolytes have been corrected on baseline ECG.
- Clinically significant pleural effusion in the previous 12 months or current ascites.
- Clinically-significant coagulation or platelet function disorder (eg, known von Willebrand's disease).
- Prior or concurrent malignancy, except for the following:
- Adequately treated basal cell or squamous cell skin cancer ii) Cervical carcinoma in situ iii) Adequately treated Stage I or II cancer from which the subject is currently in complete remission iv) Or any other cancer from which the subject has been disease-free for 3 years.
- Physical and Laboratory Test Findings
- o Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality, serious uncontrolled medical disorder or active infection that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for this study.
- Allergies and Adverse Drug Reactions
- o Intolerance to humanized monoclonal antibodies
- Other Exclusion Criteria
- Prisoners or subjects who are involuntarily incarcerated.
- Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
- Treatment with radiation within 6 weeks
- Active serious infections uncontrolled by antibiotics
- Clinically significant pulmonary disease
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Baylor Scott and White Research Institute, Charles A. Sammons Cancer Center
Dallas, Texas, 75246
University Of Kansas Medical Center
Kansas City, Kansas, 66205
UCLA
Los Angeles, California, 90095
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Memorial Sloan Kettering Cancer CEnter
New York, New York, 10065
About this study
- Establish the MTD of Lintuzumab-Ac225 as monotherapy
- Establish overall response rate (ORR) where ORR = CR + sCR+ VGPR+PR)
- Confirm the safety profile of the treatment regimen
- Estimate progression-free survival (PFS) and overall survival
Read the detailed description
The study is a multicenter, open label Phase I trial. Phase 1, dose-escalation : This study uses a 3+3 design to estimate the maximum tolerated dose (MTD).
There will be 3 escalating dose levels in the trial (0.5 μCi/kg, 1 μCi/kg, and 1.5 μCi/kg). Each dose can be administered in up to 3-8 cycles providing that the total dose received per patient does not exceed 4.5 μCi/kg.
De-escalation (decrease dose level to 0.25 μCi/kg) is planned if at the first dose level of 0.5 μCi/kg, after expanding the cohort to a maximum of 6 patients, ≥2 patient have DLTs. At the dose level of 0.25 μCi/kg, if eligible to continue receiving additional doses of the study drug, patients will receive up to 8 doses in total, with the total administered activity being 2 μCi/kg.
The starting dose level will be 0.5 μCi/kg of 225Ac-Lintuzumab administered on day 1 of each cycle. If this dose level is safe, the second dose level of 1 μCi/kg will be explored. If the starting dose level results in DLTs in ≥2 patients, the dose level of 0.25 μCi/kg will be explored.
Subjects will receive the investigational drug as a single infusion at the prescribed dose level.
Intra cohort dose escalation/ decrease is not allowed.
Minimum three to maximum six patients will be treated at each dose level, and dose escalation will proceed as follows:
- Rules for dose escalation are:
- If 0 of 3 patients have a DLT, escalate to the next dose level (Unless enrolling patients at the 0.25 µCi/kg dose level)
- If 1 of 3 patients has a DLT, expand the cohort to 6 patients
- If ≤1 of 6 patients has a DLT, escalate to the next dose level (Unless enrolling patients at the 0.25 µCi/kg dose level)
- If ≥2 of 3 or ≥2 of 6 patients have a DLT, then the previous dose is the MTD (Unless enrolling patients at the 0.25 µCi/kg level, in which case the trial is terminated)
- Three patients will start at the 0.50 uCi/kg dose. The next dose level will be 1.0 µCi/kg and the final dose level will be 1.5 µCi/kg. Dose de-escalation to 0.25 µCi/kg will occur if, at the 0.5 µCi/kg dose, there are ≥2 of 3 or ≥2 of 6 patients with a DLT.
- If a patient has not progressed nor had CR by the end of a cycle, the patient can continue treatment for a maximum of three (1.5 µCi/kg), four (1.0 µCi/kg), or eight cycles (0.25 µCi/kg and 0.50 µCi/kg).
All patients may receive GCSF support starting on Day 9 if clinically indicated and continuing until ANC>1,000.
After the dose escalation portion is completed, treat 3 additional patients at the highest established dose level to confirm MTD and establish that dose level as MTD.
- Conditions
- Refractory Multiple Myeloma
- Being tested
- Lintuzumab AC 225
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lintuzumab AC 225Drug
Also called HuM195-Ac225
Lintuzumab-Ac225 is an immunoconjugate [antibody: anti-CD 33 antibody and radioactive isotope: Actinium (225Ac)] for the treatment of multiple myeloma.
| Study group | Role | What they receive |
|---|---|---|
| IV infusion of Lintuzumab AC225 | Experimental | Starting dose - 0.5 μCi/Kg IV infusion of Lintuzumab AC225 on Day 1 of each cycle with dose escalation 1 μCi/Kg and 1.5 μCi/Kg or de-escalation to 0.25 μCi/Kg.
1 cycle = 28 days, up to 3 to 8 cycles (depending on the cohort). Receives: Drug: Lintuzumab AC 225 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated dose of Lintuzumab-AC225
establish the maximum tolerated dose as monotherapy
Measured: Through study completion, an average of 2.5 year
Adverse events- Treatment Emergent
safety of lintuzumab-Ac225
Measured: Through study completion, an average of 2.5 year
Secondary outcomes (3)
Response rates (objective response rate, complete response rate, stringent complete response rate, very good partial response rate and partial response rate)
response rate, including ORR, CR, sCR, VGPR, and PR, PFS, and OS. Efficacy assessments will include serum and urine analyses for paraprotein levels and bone marrow analyses.
Measured: Through study completion, an average of 2.5 year
Progression free survival
Progression free survival
Measured: Through study completion, an average of 2.5 year
Overall survival
Overall survival
Measured: Through study completion, an average of 2.5 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2016 (estimated)
- Study startDec 2016
- Primary completionMay 2020
- Study completionMay 2020
Why it stopped: Poor recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Actinium Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Avinash Desai, MD, Study director, Actinium Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02998047
- Sponsor's protocol ID
- Lin-AC225-MM01
- Status last verified
- Feb 2022
- First submitted
- 12 Dec 2016
- Last updated
- 8 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Lintuzumab-Ac225 in Patients With Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT02998047
- Acronym / sponsor ID
- Lin-AC225-MM01
- Conditions
- Refractory Multiple Myeloma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor recruitment
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Actinium PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Dec 2016
- Primary completion
- May 2020 (actual)
- Study completion
- May 2020 (actual)
- First posted
- 20 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- Establish the MTD of Lintuzumab-Ac225 as monotherapy
- Establish overall response rate (ORR) where ORR = CR + sCR+ VGPR+PR)
- Confirm the safety profile of the treatment regimen
- Estimate progression-free survival (PFS) and overall survival
Detailed description
The study is a multicenter, open label Phase I trial. Phase 1, dose-escalation : This study uses a 3+3 design to estimate the maximum tolerated dose (MTD).
There will be 3 escalating dose levels in the trial (0.5 μCi/kg, 1 μCi/kg, and 1.5 μCi/kg). Each dose can be administered in up to 3-8 cycles providing that the total dose received per patient does not exceed 4.5 μCi/kg.
De-escalation (decrease dose level to 0.25 μCi/kg) is planned if at the first dose level of 0.5 μCi/kg, after expanding the cohort to a maximum of 6 patients, ≥2 patient have DLTs. At the dose level of 0.25 μCi/kg, if eligible to continue receiving additional doses of the study drug, patients will receive up to 8 doses in total, with the total administered activity being 2 μCi/kg.
The starting dose level will be 0.5 μCi/kg of 225Ac-Lintuzumab administered on day 1 of each cycle. If this dose level is safe, the second dose level of 1 μCi/kg will be explored. If the starting dose level results in DLTs in ≥2 patients, the dose level of 0.25 μCi/kg will be explored.
Subjects will receive the investigational drug as a single infusion at the prescribed dose level.
Intra cohort dose escalation/ decrease is not allowed.
Minimum three to maximum six patients will be treated at each dose level, and dose escalation will proceed as follows:
- Rules for dose escalation are:
- If 0 of 3 patients have a DLT, escalate to the next dose level (Unless enrolling patients at the 0.25 µCi/kg dose level)
- If 1 of 3 patients has a DLT, expand the cohort to 6 patients
- If ≤1 of 6 patients has a DLT, escalate to the next dose level (Unless enrolling patients at the 0.25 µCi/kg dose level)
- If ≥2 of 3 or ≥2 of 6 patients have a DLT, then the previous dose is the MTD (Unless enrolling patients at the 0.25 µCi/kg level, in which case the trial is terminated)
- Three patients will start at the 0.50 uCi/kg dose. The next dose level will be 1.0 µCi/kg and the final dose level will be 1.5 µCi/kg. Dose de-escalation to 0.25 µCi/kg will occur if, at the 0.5 µCi/kg dose, there are ≥2 of 3 or ≥2 of 6 patients with a DLT.
- If a patient has not progressed nor had CR by the end of a cycle, the patient can continue treatment for a maximum of three (1.5 µCi/kg), four (1.0 µCi/kg), or eight cycles (0.25 µCi/kg and 0.50 µCi/kg).
All patients may receive GCSF support starting on Day 9 if clinically indicated and continuing until ANC>1,000.
After the dose escalation portion is completed, treat 3 additional patients at the highest established dose level to confirm MTD and establish that dose level as MTD.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IV infusion of Lintuzumab AC225 | Experimental | Drug: Lintuzumab AC 225Starting dose - 0.5 μCi/Kg IV infusion of Lintuzumab AC225 on Day 1 of each cycle with dose escalation 1 μCi/Kg and 1.5 μCi/Kg or de-escalation to 0.25 μCi/Kg. 1 cycle = 28 days, up to 3 to 8 cycles (depending on the cohort). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Confirmed diagnosis of multiple myeloma with measurable disease, as defined by the presence of M immunoglobulin protein in serum electrophoresis of at least 0.5 g/dL for IgG or 0.5 g/dL for IgA or urinary excretion of at least 200 mg monoclonal light chain per 24 hours.
- Clinical diagnosis of multiple myeloma requiring treatment that has relapsed after or proven refractory to at least three prior treatment regimens, and in the opinion of the investigator must not be candidates for any FDA approved drug known to provide clinical benefit.
- All acute toxicities from any prior therapy (radiotherapy, chemotherapy, or surgical procedures) resolved to Grade ≤ 2, NCI CTCAE.
- Serum potassium and magnesium levels within institutional normal limits. Total serum calcium or ionized calcium level must be greater than or equal to the lower limit of normal.
- Greater than 25% of myeloma plasmocytes from bone marrow must be CD33 positive.
Key exclusion criteria (32 listed)
- Sex and Reproductive Status
- Target Disease Exceptions
- Medical History and Concurrent Diseases
- Physical and Laboratory Test Findings
- o Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality, serious uncontrolled medical disorder or active infection that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for this study.
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 |
|---|---|---|
| Lintuzumab AC 225Also: HuM195-Ac225Lintuzumab-Ac225 is an immunoconjugate [antibody: anti-CD 33 antibody and radioactive isotope: Actinium (225Ac)] for the treatment of multiple myeloma. | Drug | IV infusion of Lintuzumab AC225 |
Primary outcome
Maximum Tolerated dose of Lintuzumab-AC225
Time frame: Through study completion, an average of 2.5 year
establish the maximum tolerated dose as monotherapy
Adverse events- Treatment Emergent
Time frame: Through study completion, an average of 2.5 year
safety of lintuzumab-Ac225
3 secondary outcomes
Response rates (objective response rate, complete response rate, stringent complete response rate, very good partial response rate and partial response rate)
Time frame: Through study completion, an average of 2.5 year
Progression free survival
Time frame: Through study completion, an average of 2.5 year
Overall survival
Time frame: Through study completion, an average of 2.5 year
Results and safety
The study was stopped early (reason given: Poor recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2022.
- Individual participant dataSharing planned: No
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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.
Avinash Desai, MD study director
Actinium Pharmaceuticals
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lintuzumab AC 225 in people with Refractory Multiple Myeloma, run by Actinium Pharmaceuticals at 5 sites 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 7 inclusion and 32 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: stopped early, as of the sponsor's last update on 8 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Poor recruitment). Results are not available in the source record.
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?
Maximum Tolerated dose of Lintuzumab-AC225 (time frame: Through study completion, an average of 2.5 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Mar 2022.