Clinical trial NCT05911321: Isa-Pom-Dex in Elderly/Frail Subjects With RRMM
Official title: Study of Isatuximab Plus Pomalidomide and Dexamethasone in Highly Toxicity-vulnerable Subjects With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Multiple Myeloma
Relapse
Refractory
Aging
Co-morbidity
Keywords: Pomalidomide
Isatuximab
Dexamethasone
low dose
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Genzyme, a Sanofi Company
First posted: 2023-06-22
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This research study aims to evaluate the safety and effectiveness of the combination of isatuximab, pomalidomide, and dexamethasone (Isa-Pd) for the treatment of relapsed or refractory multiple myeloma (RRMM), which refers to multiple myeloma that has returned or has not responded to prior treatment. The study will specifically investigate the impact of administering lower-than-standard doses of pomalidomide and dexamethasone. Using lower doses of pomalidomide and dexamethasone in this setting has not been approved by the Food and Drug Administration (FDA).

Detailed description: This study aims to address the challenges faced in selecting appropriate therapy for elderly or highly toxicity-vulnerable patients who are poor candidates for standard (full-dose) chemotherapy regimens. Traditional clinical trials often exclude these patients, limiting the generalizability of available data. This single-arm multicenter phase II study will enroll 49 older and/or toxicity-vulnerable patients with RRMM. The study will evaluate the safety and effectiveness of isatuximab when used in combination with pomalidomide and dexamethasone at lower than standard doses. The primary objective is to estimate the overall response rate (ORR), while secondary objectives include the estimation of additional measures of response, as well as measures of toxicity and tolerability. All participants in the trial will also be evaluated by Cancer and Aging Research Group Geriatric Assessments (CARG-GA) and patient- reported outcome (PRO) measures of quality of life (QOL). Biomarkers of aging and frailty will also be studied.

Duration of therapy:

The duration of study participation will depend on the response to the treatment. In the absence of treatment delays due to adverse events, treatment with Isa-Pd will generally continue until disease progression, unacceptable side effects, other illness or condition that prevents further study treatment, or a subject's decision to withdraw from the study. On average, subjects will most likely be treated for approximately 10 months on this study.

Duration of Follow-Up:

All participants, including those withdrawn for adverse events (AEs) will be followed after removal from study treatment until death or full subject withdrawal from the study for other reasons. Participants removed from the study treatment for unacceptable AEs will be followed for resolution or stabilization of the AEs.

Eligibility criteria: Inclusion Criteria:

1. Written informed consent obtained to participate in the study and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information (PHI). Consent must be obtained before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
2. Age ≥ 18 years at the time of consent.
3. Documented symptomatic multiple myeloma that has previously responded to therapy (partial response or better) and is relapsed or relapsed and refractory to the last line of therapy.
4. Patients must also be refractory to at least one prior line of therapy that includes an IMiD and/or a PI, and should have received at least 2 cycles of that regimen to be evaluable for refractoriness .
5. If previously treated with an anti-CD38 containing regimen, the subject must have achieved at least a PR to that line of therapy and must not have received an anti- CD38 mAb for at least 6 months prior to enrollment.
6. Willing and able to adhere to the study visit schedule and other protocol requirements based on the judgement of the investigator.
7. Predicted high risk for severe toxicity from intensive regimens for RRMM, such as standard (full-dose) DPD, DVD, KPD, KRD, Ixa-PD, or Elo-PD as each regimen was published (such regimens often use, for example, twice-weekly bortezomib at 1.3 mg/m2, lenalidomide at 25 mg, or pomalidomide 4 mg). High-risk is defined as one of the following:

A. Score ≥ 2 (indicating "frail") on the International Myeloma Working Group instrument (IMWG; Palumbo et al. \[Blood 2015\]) B.KPS ≤ 70

C. Not meeting criteria A or B above but felt by treating clinician to not be a candidate for a standard full-dose regimen on account of one of the following:

i) History of clinically significant non-hematologic grade ≥3 (NCI CTCAE, version 5.0) toxicity attributed to prior anticancer therapy ii) History of requiring dose-reduction of at least two separate anticancer drugs during prior therapy for multiple myeloma.

Exclusion Criteria:

All subjects meeting any of the listed exclusion criteria at baseline with be excluded from study participation.

1. Anti-myeloma treatment within 2 weeks of cycle 1 day 1
2. Prior treatment with pomalidomide
3. Any monoclonal antibody therapy within the previous 30-days
4. Anti-CD38 monoclonal antibody therapy within the previous 6 months
5. Autologous stem cell transplantation within 12 weeks of day 1 of cycle 1
6. Subjects felt to not be candidates by treating physician for any systemic therapy due to excessive comorbidities, frailty, impaired performance status, or other severe limitations. Such limitations can be conceptualized generally as making subjects exceedingly high risk for any systemic treatment. These limitations often stem from medical comorbidities unrelated to MM and they are hence unlikely to improve with MM therapy.

Primary outcomes:
measure: Overall response Rate (ORR)
timeFrame: Up to 12 weeks
Secondary outcomes:
measure: Treatment related adverse events rate
timeFrame: Up to 12 weeks
measure: Treatment failure-free survival (TFFS)
timeFrame: Up to 3 years
measure: Maximum depth of response
timeFrame: Up to 12 weeks
measure: Clinical benefit rate (CBR)
timeFrame: Up to 12 weeks
measure: Bone marrow minimal residual disease (MRD) negativity
timeFrame: Up to 12 weeks
measure: Time to first response
timeFrame: Up to 12 weeks
measure: Time to best response
timeFrame: Up to 12 weeks
measure: Duration of response
timeFrame: Up to 3 years
measure: Progression-free survival (PFS)
timeFrame: Up to 3 years
measure: Median time to next treatment (TTNT)
timeFrame: Up to 3 years
measure: Overall survival
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Atrium Health Wake Forest Baptist Medical Center
state: North Carolina
Study officials:
affiliation: UNC Lineberger Comprehensive Cancer Center
name: Eben I Lichtman, MD
role: PRINCIPAL_INVESTIGATOR
References: