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Recurrent Plasma Cell MyelomaPhase 1NCT04956302

Panobinostat in Combination With Daratumumab, Bortezomib and Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma

A Phase 1 study testing Bortezomib, Daratumumab and Hyaluronidase-fihj and Dexamethasone in people with Recurrent Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, run by Abdullah Khan at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase I trial studies the possible benefits and side effects of adding panobinostat to a combination of daratumumab, bortezomib and dexamethasone in treating patients with multiple myeloma that has come back (relapsed) or has not responded to treatment (refractory). Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Bortezomib, Daratumumab and Hyaluronidase-fihj and Dexamethasone
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteUnited States
Study dates
27 Sep 2021to 16 Jun 2022
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 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients 18-75 years of age with evidence of relapsed or refractory disease as defined by IMWG criteria and measurable disease as defined by any of the following:
  • Serum M-protein >= 0.5 g/dl (>= 10 g/l)
  • Urine monoclonal protein >= 200 mg/24h
  • Involved free light chain (FLC) level >= 10mg/dl (>= 100mg/l) and an abnormal serum free light chain ratio (< 0.26, or > 1.65)
  • Patients must have had at least 1 prior line of therapy including lenalidomide or cyclophosphamide, V or other PI, with or without ASCT
  • Patients with progressive disease (PD) as best response on V are excluded
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  • Patients with PD on D-based therapy may be eligible at the discretion of the treating physician
  • Refractory (progressed on or within 120 days of treatment) to their last treatment
  • Patients must be off last treatment for at least 2 weeks by the beginning of treatment on this protocol
  • Hemoglobin >= 7g/dL
  • Absolute neutrophil count (ANC) >= 1000/uL
  • Platelets >= 70,000/uL
  • If plasma cell percentage on bone marrow biopsy aspirate or core is > 30%, platelet requirement will be adjusted to 50,000/ul
  • Total bilirubin < 1.5 mg/dL
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/alkaline phosphatase < 2 x the upper limit of normal (ULN)
  • Serum creatinine < 2mg/dL or calculated creatinine clearance of >= 30ml/min using Modification of Diet in Renal Disease Study (MDRD) formula
  • Left ventricular ejection fraction >= 30%; baseline echocardiogram (ECHO) is not required
  • No uncontrolled arrhythmias
  • No New York Heart Association class III-IV heart failure
  • 12-lead electrocardiogram (ECG) with QT interval calculated by Fridericia Formula (QTcF) interval of =< 450 msec
  • Patient must be able to swallow capsule or tablet
  • Patients must provide informed consent
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of < 2
  • Women of child bearing potential (WOCBP) must commit to either abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously. This includes one highly effective form of contraception (tubal ligation, intrauterine device [IUD], hormonal [birth control pills, injections, hormonal patches, vaginal rings or implants] or partner's vasectomy) and one additional effective contraceptive method (male latex or synthetic condom, diaphragm, or cervical cap). Contraception must begin 4 weeks prior to dosing and continue to 6 months after study treatment ending. Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy
  • Investigators shall counsel WOCBP and male participants who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy
  • A negative pregnancy test will be required for all WOCBP within 24 hours before starting treatment drugs
  • Breast feeding is not permitted
  • Male patients must agree to use an adequate method of contraception (latex or synthetic condom) for the duration of the study and up to 6 months after study treatment ending
  • Criteria also applies to azoospermic males
  • Males should refrain from sperm donation during this time and continue for 6 months after study treatment ending

Who cannot join

  • Patients with active (untreated or relapsed) central nervous system (CNS) metastasis of myeloma
  • Patients with Waldenstrom macroglobulinemia, primary amyloid light-chain (AL) amyloidosis, primary plasma cell leukemia, or polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome
  • Patients with secondary plasma cell leukemia are permitted
  • Patients with peripheral neuropathy > National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade 2
  • Patients receiving concurrent corticosteroids at the time protocol therapy is initiated other than for physiologic maintenance treatment
  • Concurrent use of complementary or alternative medicines that would confound the interpretation of toxicities and antitumor activity of the study drugs
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  • Patients with known allergies, hypersensitivity, or intolerance to panobinostat, daratumumab, or bortezomib
  • Unacceptable respiratory risk factors defined by any one of the following criteria:
  • Chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) less than 50% of predicted normal
  • Moderate or severe persistent asthma within the past 2 years, or currently has uncontrolled asthma of any classification
  • Unacceptable cardiac risk factors defined by any of the following criteria:
  • Patients with congenital long QT syndrome
  • Any history of ventricular fibrillation or torsade de pointes
  • Bradycardia defined as heart rate (HR) < 50 beats per minute (bpm)
  • Left ventricular ejection fraction < 30%
  • Patients who have received targeted or investigational agents within 2 weeks or within 5 half-lives of the agent and active metabolites (whichever is shorter) and who have not recovered from side effects of those therapies
  • Patients who have undergone major surgery =< 2 weeks prior to starting study drug or who have not recovered from the side-effects of surgery
  • Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required
  • Patients with active hepatitis B (defined as hepatitis B virus surface antigen positive [HBsAg+]); HBV screening is required prior to beginning therapy
  • Patients with prior hepatitis B vaccine are permitted (defined as hepatitis B virus surface antigen negative [HBsAg-], hepatitis B virus surface antibody positive [Anti-HBs+], hepatitis B virus core antibody negative (Anti-HBc-])
  • Non-active hepatitis B (HBsAg-, Anti-HBs+, hepatitis B virus core antibody positive [Anti-HBc+]) may only be enrolled following approval by the sponsor after consideration of risk of reactivation (additional screening and monitoring for hepatitis B and consultation with a liver disease specialist may be required)
  • Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention, other than non-melanoma skin cancer and carcinoma in situ of the cervix, should not be enrolled
  • Patients are not considered to have a "currently active" malignancy if they have completed therapy for a prior malignancy, are disease free from a prior malignancy for >= 3 yrs, and are considered by their physician to be less than 30% risk of relapse
  • Patients with a history of gastrointestinal surgery or other procedure that might, in the opinion of the investigator(s), interfere with the absorption or swallowing of the study drugs
  • Patients with any significant history of non-compliance to medical regimens or unwilling or unable to comply with the instructions given to them by the study staff
  • Any other medical condition, including mental illness or substance abuse, deemed by the investigator(s) to likely interfere with the patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: A Phase I Study of Panobinostat in Combination With Daratumumab, Bortezomib, and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma

This phase I trial studies the possible benefits and side effects of adding panobinostat to a combination of daratumumab, bortezomib and dexamethasone in treating patients with multiple myeloma that has come back (relapsed) or has not responded to treatment (refractory). Panobinostat may stop or slow multiple myeloma by blocking the growth of new blood vessels necessary for cancer growth. Giving panobinostat in combination with daratumumab, bortezomib and dexamethasone may work better in treating relapsed/refractory multiple myeloma.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate the safety and tolerability of Farydak (panobinostat lactate)/Darzalex Faspro (daratumumab and hyaluronidase-fihj)/Velcade (bortezomib)/dexamethasone (FDVd) in patients with relapsed/refractory multiple myeloma (RRMM) who have previously received one line of therapy including lenalidomide or cyclophosphamide, bortezomib (V) or other proteasome inhibitor (PI), with or without autologous stem cell transplant (ASCT).

SECONDARY OBJECTIVES:

  1. To evaluate the overall response rate (ORR) (per International Myeloma Working Group [IMWG] criteria) of FDVd.

II. Determine the time to response (TTR). III. Determine the duration of response (DOR). IV. Determine the progression-free survival (PFS) at 1 year. V. Determine the overall survival (OS) at 1 year.

CORRELATIVE OBJECTIVES:

  1. Baseline and end of-study plasma cell expression of CD38. II. Changes in lymphocyte subsets with therapy. III. Baseline and end-of study analysis of total number and ratio of regulatory T cells (Tregs) with CD38+ expression.

IV. Check minimal residual disease (MRD) negativity rates by next generation sequencing in patients who attain and maintain very good partial response (VGPR) or better for at least three months.

OUTLINE: This is a dose-escalation study of panobinostat.

Patients receive panobinostat orally (PO) once daily (QD) on days 1, 3, 5, 15, 17, 19, daratumumab and hyaluronidase-fihj subcutaneously (SC) on days 1, 8, 15, 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of subsequent cycles, bortezomib SC on days 1, 8, 15, 22 and dexamethasone PO (intravenously [IV] on days of daratumumab and hyaluronidase-fihj administration) QD on days 1, 8, 15, 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up on days 30 and 60.

Being tested
Bortezomib, Daratumumab and Hyaluronidase-fihj, Dexamethasone, Panobinostat Lactate
Medical subject headings
Multiple Myeloma

What participants receive

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

  • BortezomibDrug

    Also called [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341

    Given SC

  • Daratumumab and Hyaluronidase-fihjDrug

    Also called DARA Co-formulated with rHuPH20, DARA/rHuPH20, Daratumumab + rHuPH20, Daratumumab with rHuPH20

    Given SC

  • DexamethasoneDrug

    Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex

    Given PO or IV

  • Panobinostat LactateDrug

    Also called Farydak

    Given PO

Study groups in NCT04956302
Study groupRoleWhat they receive
Treatment (panobinostat, daratumumab, bortezomib, dexa)ExperimentalPatients receive panobinostat PO QD on days 1, 3, 5, 15, 17, 19, daratumumab and hyaluronidase-fihj SC on days 1, 8, 15, 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of subsequent cycles, bortezomib SC on days 1, 8, 15, 22 and dexamethasone PO (IV on days of daratumumab and hyaluronidase-fihj administration) QD on days 1, 8, 15, 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Bortezomib; Drug: Daratumumab and Hyaluronidase-fihj; Drug: Dexamethasone; Drug: Panobinostat Lactate

What is being measured

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

  1. Recommended phase 2 dose

    A standard "3+3" design will be used to determine the safe and tolerable dose level.

    Measured: End of cycle 1 (1 cycle = 28 days)

  2. Incidence of adverse events

    Assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.

    Measured: Up to 3 years

Secondary outcomes (6)

  1. Time to progression

    Cumulative incidence rates will be calculated and compared using Gray's test accounting for competing risks.

    Measured: From start of treatment until objective tumor progression, assessed up to 3 years

  2. Progression-free survival

    Will be calculated using the Kaplan-Meier method. Will be calculated together with 95% confidence intervals, and log-rank test will be used for the comparison between patient subgroups.

    Measured: From start of treatment until disease progression or death, assessed at 1 year

  3. Objective response rate (ORR)

    ORR will be defined as the total number of subjects whose best response is partial response (PR) or better divided by the number of patients. ORR will be reported overall as well as by dose level, with 95% binomial exact confidence intervals. Comparison of ORR among patient subgroups will be conducted using Fisher exact test.

    Measured: Up to 3 years

  4. Time to response

    Cumulative incidence rates will be calculated and compared using Gray's test accounting for competing risks.

    Measured: From start of treatment until measurement criteria are first met for PR, very good partial response, or complete response, assessed up to 3 years

  5. Duration of overall response

    Will be calculated using the Kaplan-Meier method. Will be calculated together with 95% confidence intervals, and log-rank test will be used for the comparison between patient subgroups.

    Measured: From the time measurement criteria are first met for partial response or better (whichever status is recorded first) until the first date of progressive disease or death, assessed up to 3 years

  6. Overall survival

    Will be calculated using the Kaplan-Meier method. Will be calculated together with 95% confidence intervals, and log-rank test will be used for the comparison between patient subgroups.

    Measured: From start of treatment to the date of his or her death, assessed at 1 year

Timeline

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

  1. First posted9 Jul 2021
  2. Study start27 Sep 2021
  3. Primary completion16 Jun 2022
  4. Study completion16 Jun 2022

Why it stopped: PI Decision

Resources

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
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04956302
Sponsor's protocol ID
OSU-21005
Other IDs
NCI-2021-04261
Status last verified
Jun 2024
First submitted
30 Jun 2021
Last updated
6 Jun 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Bortezomib, Daratumumab and Hyaluronidase-fihj and Dexamethasone in people with Recurrent Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, run by Abdullah Khan 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 30 inclusion and 26 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 6 Jun 2024. 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 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: PI Decision). 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?

Recommended phase 2 dose (time frame: End of cycle 1 (1 cycle = 28 days)). 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?

On the ClinicalTrials.gov record for NCT04956302.

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 6 Jun 2024.

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