Relapsed or Refractory Multiple MyelomaPhase 1/2NCT05408026
Study of Combination POM, BTZ, Low-Dose DEX, and DARA (PVD-DARA) in Patients With RRMM
A Phase 1/2 study testing Daratumumab and Pomalidomide in people with Relapsed or Refractory Multiple Myeloma, run by Alliance Foundation Trials, LLC..
Trial summary
This phase II clinical trial design with a safety run-in period will be used to assess the rate of VGPR or better for the combination PVD-Dara in the treatment of RRMM. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed or Refractory Multiple Myeloma
- What is being tested?
- Daratumumab and Pomalidomide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2022to Feb 2026
- Phase
- Phase 1/2
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed diagnosis of symptomatic multiple myeloma.
- Evidence of disease progression or refractoriness to 1 to 3 prior lines of therapy by IMWG standard criteria.
- Prior exposure to lenalidomide and a proteasome inhibitor is mandatory.
- Daratumumab naïve patients or Daratumumab exposed patients who are not refractory to weekly or bi-weekly daratumumab.
- Measurable disease:
- Serum M protein ≥ 0.5 g/dL
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- Urine M protein ≥ 200 mg/24 hours
- Involved serum free light chains ≥ 10 mg/dL AND an abnormal serum free light chain ratio
- ECOG Status 0-2 ≤ 14 days prior to registration
- Adequate organ function including ≤ 14 days prior to registration defined as:
- ANC ≥ 1.0 x 10^9/L. (Patients cannot have received G-CSF or GM-CSF within 1 week of screening or pegfilgrastim within 2 weeks of screening)
- Platelets ≥ 75 x 10^9/L
- Calculated Creatinine Clearance ≥ 30 mL/min
- Total Bilirubin ≤ 1.5 x ULN except for patients with a history of elevated total bilirubin, such as in Gilbert's
- AST, AP, ALT ≤ 3 x ULN
- Hepatic Child-Pugh score at worse A (eligible for the phase 2 part but not for the Run-in-Period).
- Adequate cardiac function within 8 weeks prior to registration defined as LVEF ≥ 40%.
Who cannot join
- Disease refractory to weekly or bi-weekly daratumumab therapy.
- Female patients who are lactating or have a positive serum pregnancy test ≤ 14 days from registration during the screening period.
- Failure to have fully recovered from the reversible effects of prior anti-cancer therapy.
- Major surgery within 14 days before registration.
- Focal radiation therapy within 14 days prior to randomization with the exception of palliative radiotherapy for symptomatic management but not on measurable extramedullary plasmacytoma.
- Disease-related central nervous system involvement.
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- Plasma cell leukemia, AL amyloidosis, or POEMS syndrome.
- The subject has uncontrolled significant intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled congestive heart failure, New York Heart Association Class III-IV, unstable angina pectoris, stroke, myocardial infarction, uncontrolled cardiac arrhythmias < 6 months prior to registration, or uncontrolled hypertension.
- Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
- Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
- Known GI disease or GI procedure that could interfere with the oral absorption of study medication including difficulty swallowing.
- Concurrent malignancy except for treated non-melanoma skin cancer, cervical carcinoma in situ and low-risk prostate CA being monitored without treatment.
- Grade 2 and higher peripheral neuropathy on clinical examination ≤ 14 days prior to registration.
- Chemotherapy ≤ 14 days prior to registration.
- Exposure to an investigational drug (including investigational vaccine) or invasive investigational medical device for any indication within 4 weeks or 5 pharmacokinetic half-lives, whichever is longer.
- Patients with known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal; moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification. Note.
- Moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification. Note that participants who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate.
- Patients who have a contraindication to the use of any form of anticoagulation or antiplatelet agents.
- Patient who are on a strong CYP34A or CYP1A2 inducer or inhibitors
- Patients with Hepatic Child-Pugh score B and C. Note that Hepatic Child-Pugh score A are excluded from the Run-in-Period of the trial
- Patient is:
- seropositive for human immunodeficiency virus (HIV).
- seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
- seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy).
About this study
Official title: A Phase II, Multicenter, Open-Label Study of the Combination of Pomalidomide, Bortezomib, Low-Dose Dexamethasone, and Daratumumab in Patients With Relapsed or Refractory Multiple Myeloma
This phase II clinical trial design with a safety run-in period will be used to assess the rate of VGPR or better for the combination PVD-Dara in the treatment of RRMM.
Read the detailed description
A phase II clinical trial design, including an initial safety run-In period, will be used to assess the rate of VGPR or better for the combination PVD-Dara in the treatment of relapsed or refractory multiple myeloma.
In the run-in period, a maximum of 12 patients will be enrolled onto the trial using the initially proposed regimen and then the trial will be temporarily closed to enrollment, until safety data is reviewed for these patients. Adverse events during the first cycle of treatment of the initially proposed regimen will be closely monitored. If the safety criteria have been met as defined in the protocol, then the trial will reopen to enrollment using the regimen as planned until a total of 72 patients have been enrolled. If safety criteria have not been met as per protocol, then the treatment regimen will be modified for the second cohort of 12 patients after discussion with the study team taking into consideration that if intolerability is due to neutropenia the regimen will be modified by lowering the dose of pomalidomide.
The phase II will begin once the safe doses have been determined in the Run-in period. this Phase II clinical trial was designed to assess whether this 4-agent combination yields a response rate of VGPR or better in more than 65% of patients.
For the regimen found tolerable in the safety period, a two-stage Phase II clinical trial design was chosen to assess whether the VGPR or better response rate is at most 50% against the alternative that the VGPR or better response rate is at least 65%.
- Conditions
- Relapsed or Refractory Multiple Myeloma
- Being tested
- Daratumumab, Pomalidomide
- Medical subject headings
- Recurrence, Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DaratumumabDrug
Also called Dexamethasone
Daratumumab (and hyaluronidase) will be given over 3-5 minutes subcutaneously (under the skin) in the clinic at alternating left/right abdominal sites. Patient will take dexamethasone orally (by mouth) either before coming to clinic or in clinic, before other medications.
Only for the first cycle, patient will receive on Day 1 daratumumab (which is mixed with a compound called hyaluronidase) and dexamethasone, 1 day before patient start the other 2 medications.
PomalidomideDrug
Also called Bortezomib
On day 2 of cycle 1, patient will start the other medications and will therefore receive bortezomib administered subcutaneously (SC) over 3-5 minutes and dexamethasone given orally (by mouth), either before coming to clinic or in clinic, before bortezomib. Patient will also start pomalidomide on the same day, which patient will take that evening at home and every evening for 21 days.
| Study group | Role | What they receive |
|---|---|---|
| Combination of Pomalidomide, Bortezomib, Low-Dose Dexamethasone, and Daratumumab | Experimental | Combination of Pomalidomide, Bortezomib, Low-Dose Dexamethasone, and Daratumumab Receives: Drug: Daratumumab; Drug: Pomalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety Run-In Stage: Adverse events (AEs) will be assigned a grade and attribution using CTCAE v5.0 to determine the presence of dose-limiting toxicities (DLT).
DLTs will be used to assess the safety profile \& determine tolerability of PVD-DARA in patients with RRMM. A DLT is the occurrence of any below toxicity during the first cycle probably, possibly or definitely related to study treatment:
- Grade 4 neutropenia
- Febrile neutropenia
- Grade 4 thrombocytopenia
- Grade 3 thrombocytopenia w/ bleeding
- Grade 4 anemia, unexplained by underlying disease
- Any non-hematological toxicity Grade ≥ 3, except:
- Alopecia
- Grade 3 nausea/vomiting/diarrhea for < 72 hours w/ antiemetic \& other supportive care
- Grade 3 fatigue for < 1 week
- Grade ≥ 3 isolated electrolyte abnormalities for ≤ 72 hours, not clinically complicated, resolve spontaneously/respond to conventional medical interventions
- Grade ≥ 3 amylase/lipase elevation not associated w/ symptoms/clinical manifestations of pancreatitis
- Grade 3 tumor lysis syndrome for ≤ 72 hours, not clinically complicated, resolves spontaneously/responds to conventional medical intervention
Measured: 4-9 months
Phase II: To estimate the rate of Very Good Partial Response (VGPR) or better after 8 cycles of the combination PVD-DARA in patients with RRMM, including those with prior exposure to daratumumab
To estimate the rate of VGPR or better after 8 cycles of the combination PVD-DARA in patients with RRMM, including those with prior exposure to daratumumab
Measured: 36 months
Secondary outcomes (6)
Rate of Adverse Events Grade ≥ 3 [Toxicity Profile]
The toxicity profile will be summarized by determining the rate of patients with a grade 3 or higher adverse event.
Measured: 4 years
Rate of Dose Omission [Toxicity Profile]
The toxicity profile will be summarized by determining the rate of patients at least one omitted dose.
Measured: 4 years
Rate of Dose Modification [Toxicity Profile]
The toxicity profile will be summarized by determining the rate of patients at least one modified dose.
Measured: 4 years
To determine the overall response rate (ORR, including sCR, CR, VGPR, PR) after 8 cycles of the combination PVD-DARA in patients with RRMM, including patients previously exposed to daratumumab
To determine the overall response rate (ORR, including sCR, CR, VGPR, PR) after 8 cycles of the combination PVD-DARA in patients with RRMM, including patients previously exposed to daratumumab
Measured: 4 years
To determine the Progression Free Survival (PFS) for the combination PVD-DARA in patients with RRMM, including patients previously exposed to daratumumab
To determine the Progression Free Survival (PFS) for the combination PVD-DARA in patients with RRMM, including patients previously exposed to daratumumab
Measured: 4 years
To determine the overall survival for the combination PVD-DARA in patients with RRMM, including patients previously exposed to daratumumab
To determine the overall survival for the combination PVD-DARA in patients with RRMM, including patients previously exposed to daratumumab
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2022
- Study start1 Oct 2022 (estimated)
- Primary completion1 Oct 2025 (estimated)
- Study completionFeb 2026 (estimated)
Why it stopped: Study withdrawn, trial therapy deemed no longer novel and there was a lack of site interest.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed or 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alliance Foundation Trials, LLC.
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen, LP, Celgene
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05408026
- Sponsor's protocol ID
- AFT-35
- Status last verified
- Jan 2023
- First submitted
- 6 May 2022
- Last updated
- 27 Jan 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Multicenter, Open-Label Study of the Combination of Pomalidomide, Bortezomib, Low-Dose Dexamethasone, and Daratumumab in Patients With Relapsed or Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT05408026
- Acronym / sponsor ID
- AFT-35
- Conditions
- Relapsed or Refractory Multiple Myeloma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study withdrawn, trial therapy deemed no longer novel and there was a lack of site interest.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Alliance Foundation Trials, LLC.University, hospital or other
- Collaborators
- Janssen, LP, Celgene
- Study start
- 1 Oct 2022 (estimated)
- Primary completion
- 1 Oct 2025 (estimated)
- Study completion
- Feb 2026 (estimated)
- First posted
- 7 Jun 2022 (actual)
- 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.
This phase II clinical trial design with a safety run-in period will be used to assess the rate of VGPR or better for the combination PVD-Dara in the treatment of RRMM.
Detailed description
A phase II clinical trial design, including an initial safety run-In period, will be used to assess the rate of VGPR or better for the combination PVD-Dara in the treatment of relapsed or refractory multiple myeloma.
In the run-in period, a maximum of 12 patients will be enrolled onto the trial using the initially proposed regimen and then the trial will be temporarily closed to enrollment, until safety data is reviewed for these patients. Adverse events during the first cycle of treatment of the initially proposed regimen will be closely monitored. If the safety criteria have been met as defined in the protocol, then the trial will reopen to enrollment using the regimen as planned until a total of 72 patients have been enrolled. If safety criteria have not been met as per protocol, then the treatment regimen will be modified for the second cohort of 12 patients after discussion with the study team taking into consideration that if intolerability is due to neutropenia the regimen will be modified by lowering the dose of pomalidomide.
The phase II will begin once the safe doses have been determined in the Run-in period. this Phase II clinical trial was designed to assess whether this 4-agent combination yields a response rate of VGPR or better in more than 65% of patients.
For the regimen found tolerable in the safety period, a two-stage Phase II clinical trial design was chosen to assess whether the VGPR or better response rate is at most 50% against the alternative that the VGPR or better response rate is at least 65%.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combination of Pomalidomide, Bortezomib, Low-Dose Dexamethasone, and Daratumumab | Experimental | Drug: Daratumumab, Drug: PomalidomideCombination of Pomalidomide, Bortezomib, Low-Dose Dexamethasone, and Daratumumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Histologically confirmed diagnosis of symptomatic multiple myeloma.
- Evidence of disease progression or refractoriness to 1 to 3 prior lines of therapy by IMWG standard criteria.
- Prior exposure to lenalidomide and a proteasome inhibitor is mandatory.
- Daratumumab naïve patients or Daratumumab exposed patients who are not refractory to weekly or bi-weekly daratumumab.
- Measurable disease:
Key exclusion criteria (24 listed)
- Disease refractory to weekly or bi-weekly daratumumab therapy.
- Female patients who are lactating or have a positive serum pregnancy test ≤ 14 days from registration during the screening period.
- Failure to have fully recovered from the reversible effects of prior anti-cancer therapy.
- Major surgery within 14 days before registration.
- Focal radiation therapy within 14 days prior to randomization with the exception of palliative radiotherapy for symptomatic management but not on measurable extramedullary plasmacytoma.
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 |
|---|---|---|
| DaratumumabAlso: DexamethasoneDaratumumab (and hyaluronidase) will be given over 3-5 minutes subcutaneously (under the skin) in the clinic at alternating left/right abdominal sites. Patient will take dexamethasone orally (by mouth) either before coming to clinic or in clinic, before other medications. Only for the first cycle, patient will receive on Day 1 daratumumab (which is mixed with a compound called hyaluronidase) and dexamethasone, 1 day before patient start the other 2 medications. | Drug | Combination of Pomalidomide, Bortezomib, Low-Dose Dexamethasone, and Daratumumab |
| PomalidomideAlso: BortezomibOn day 2 of cycle 1, patient will start the other medications and will therefore receive bortezomib administered subcutaneously (SC) over 3-5 minutes and dexamethasone given orally (by mouth), either before coming to clinic or in clinic, before bortezomib. Patient will also start pomalidomide on the same day, which patient will take that evening at home and every evening for 21 days. | Drug | Combination of Pomalidomide, Bortezomib, Low-Dose Dexamethasone, and Daratumumab |
Primary outcome
Safety Run-In Stage: Adverse events (AEs) will be assigned a grade and attribution using CTCAE v5.0 to determine the presence of dose-limiting toxicities (DLT).
Time frame: 4-9 months
DLTs will be used to assess the safety profile \& determine tolerability of PVD-DARA in patients with RRMM. A DLT is the occurrence of any below toxicity during the first cycle probably, possibly or definitely related to study treatment: * Grade 4 neutropenia * Febrile neutropenia * Grade 4 thrombocytopenia * Grade 3 thrombocytopenia w/ bleeding * Grade 4 anemia, unexplained by underlying disease * Any non-hematological toxicity Grade ≥ 3, except: * Alopecia * Grade 3 nausea/vomiting/diarrhea for < 72 hours w/ antiemetic \& other supportive care * Grade 3 fatigue for < 1 week * Grade ≥ 3 isolated electrolyte abnormalities for ≤ 72 hours, not clinically complicated, resolve spontaneously/respond to conventional medical interventions * Grade ≥ 3 amylase/lipase elevation not associated w/ symptoms/clinical manifestations of pancreatitis * Grade 3 tumor lysis syndrome for ≤ 72 hours, not clinically complicated, resolves spontaneously/responds to conventional medical intervention
Phase II: To estimate the rate of Very Good Partial Response (VGPR) or better after 8 cycles of the combination PVD-DARA in patients with RRMM, including those with prior exposure to daratumumab
Time frame: 36 months
To estimate the rate of VGPR or better after 8 cycles of the combination PVD-DARA in patients with RRMM, including those with prior exposure to daratumumab
6 secondary outcomes
Rate of Adverse Events Grade ≥ 3 [Toxicity Profile]
Time frame: 4 years
Rate of Dose Omission [Toxicity Profile]
Time frame: 4 years
Rate of Dose Modification [Toxicity Profile]
Time frame: 4 years
To determine the overall response rate (ORR, including sCR, CR, VGPR, PR) after 8 cycles of the combination PVD-DARA in patients with RRMM, including patients previously exposed to daratumumab
Time frame: 4 years
To determine the Progression Free Survival (PFS) for the combination PVD-DARA in patients with RRMM, including patients previously exposed to daratumumab
Time frame: 4 years
To determine the overall survival for the combination PVD-DARA in patients with RRMM, including patients previously exposed to daratumumab
Time frame: 4 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2023.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Daratumumab and Pomalidomide in people with Relapsed or Refractory Multiple Myeloma, run by Alliance Foundation Trials, LLC..
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 24 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: withdrawn, as of the sponsor's last update on 27 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
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 combined 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.
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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Safety Run-In Stage: Adverse events (AEs) will be assigned a grade and attribution using CTCAE v5.0 to determine the presence of dose-limiting toxicities (DLT). (time frame: 4-9 months). 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 27 Jan 2023.