Systemic Anti-Cancer Therapy Dose Modifications for Individuals With Duffy Null Phenotype
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Dexamethasone, Bortezomib, LENALIDOMIDE, Daratumumab.
- Who it may be relevant to
- Registry conditions: Multiple Myeloma, Triple Negative Breast Cancer, Duffy Blood Group, Chemokine Receptor Gene Mutation, Duffy Blood Group, Chemokine Receptor Gene C.-67T>C. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
A Pilot Study of Duffy Null-Specific Dose Modifications for Individuals With Duffy Null Phenotype Receiving Standard of Care Systemic Anti-Cancer Therapies
Overview
This study is comprised of a main study, an observational study, and optional survey studies. The main study is being done to see whether using Duffy null specific treatment dosing guidelines can reduce or delay dose modifications and avoid neutropenic fever (fever in the setting of low neutrophils) for people with Duffy null phenotype receiving treatment for multiple myeloma or triple negative breast cancer. The observational study is to collect dose modification and neutropenic fever information on patients who do not have the Duffy null phenotype and receive the same standard of care regimens to see if there are differences in dose modifications and neutropenic fever between the two groups. The survey studies seek to understand general health experiences and preferences and experiences specific to people with Duffy null phenotype. Study Drugs Include: * Daratumumab * lenalidomide * bortezomib * dexamethasone * carboplatin * paclitaxel * pembrolizumab * cyclophosphamide * doxorubicin
Detailed description
This research study is a parallel arm, pragmatic, pilot study. As a pilot study it will be the first time investigators are examining using Duffy null specific dose modification guidelines for treatment dosing for participants with multiple myeloma or triple negative breast cancer receiving treatment of:
* Daratumumab, lenalidomide, bortezomib and dexamethasone for multiple myeloma * Paclitaxel, carboplatin, doxorubicin, cyclophosphamide, and pembrolizumab for triple negative breast cancer The study will also be looking to understand health experiences of participants with and without the Duffy null phenotype through optional observational and survey studies.
The U.S. Food and Drug Administration (FDA) has approved daratumumab, lenalidomide, bortezomib and dexamethasone as a treatment option for some individuals with multiple myeloma. This study uses these drugs in ways typically used in clinical practice but not in ways approved by the FDA. Specifically, the FDA approval does not approve the use of this treatment for more than 4 cycles prior to stem cell transplantation or in those who are deferring or ineligible for transplantation, or with the specific drug dosing used in this study. These unapproved modifications, however, are supported by treatment guidelines from the National Comprehensive Cancer Network.
The U.S. Food and Drug Administration (FDA) has approved paclitaxel, carboplatin, doxorubicin, cyclophosphamide, and pembrolizumab for preoperative treatment of triple negative breast cancer. This study uses these drugs in ways typically used in clinical practice but not in ways approved by the FDA. Specifically, the FDA approval does not approve the use of this treatment in individuals who have 1-10% ER or PR positivity (called low-level positivity). This population, however, is often treated as having ER or PR negative disease, and this treatment decision is noted as acceptable by the National Comprehensive Cancer Network.
The research study procedures include screening for eligibility, clinical exams-medical history/physical exam, study treatment, and surveys.
The study treatment for the multiple myeloma group will be Bortezomib, Daratumumab, Lenalidomide, and Dexamethasone given over a 28 day cycle for 6 cycles.
The study treatment for the triple negative breast cancer group will receive treatment in two phases.
* The first phase will be Paclitaxel, carboplatin, and pembrolizumab over a 21 day cycle for 4 cycles. * The second phase will be doxorubicin, cyclophosphamide, and pembrolizumab over a 21 day cycle for 4 cycles.
Participants who elect to take part in the optional observational studies will provide use of medical records for comparison of Duffy null and non-Duffy null populations. Participants who elect to take part in the optional short surveys will complete the short surveys.
It is expected that about 90 people will take part in this research study, 60 in the treatment study, and 30 in the observational study.
The Principal Investigator of this study and Dana-Farber Cancer Institute are the primary sponsors of this study.
Interventions
- Drug Dexamethasone
Tablet, taken orally - Drug Bortezomib
Intravenous infusion - Drug LENALIDOMIDE
Tablet, taken orally - Drug Daratumumab
Intravenous infusion - Drug Carboplatin
Intravenous infusion - Drug Paclitaxel
Intravenous infusion - Drug Pembrolizumab
Intravenous infusion - Drug Cyclophosphamide
Intravenous infusion - Drug Doxorubicin
Intravenous infusion
Primary outcome measures
- Avoided or reduced systemic anticancer therapy (SACT) modifications per cycle [Time frame: Avoided or reduced modifications determined by ANC (anticancer therapy) values in each treatment cycle. Coh 1 (Dara-RVD) is 6 cycles(cycle=28 dys)-ANC assessed days 1, 8, 15, & 22. Coh 2 has 8 cycles (cycle=21 dys)-ANC assessed days 1, 8, & 15]
- Overall cumulative incidence of neutropenic fever [Time frame: Neutropenic fever is assessed from treatment initiation through the end of protocol-based treatment. It will be assessed at baseline and before treatment dosing during each cycle (Coh1 is 6 cycles (cycle=28 days); Coh 2 is 8 cycles (cycle=21 days)).]
Secondary outcome measures (3)
- Avoided or reduced systemic anticancer therapy (SACT) modifications per ANC check (i.e. per week) [Time frame: Avoided or reduced modifications determined by ANC (anticancer therapy) values during each treatment cycle. Coh1 (Dara-RVD) is 6 cycles(cycle=28 dys)- ANC assessed on days 1, 8, 15, & 22. Coh 2 is 8 cycles (cycle=21 dys)- ANC assessed days 1, 8, & 15]
- Cumulative incidence of neutropenic fever within regimen [Time frame: Neutropenic fever will be assessed from initiation of treatment through end of the last cycle of protocol-based treatment; cycle length and number varies by phase of therapy. It will be assessed at baseline and before therapy dosing during each cycle.]
- Relative dose intensity (RDI) [Time frame: Dosing, for the calculation of RDI, will be assessed immediately at the time of protocol-specified treatment from the initiation of treatment through treatment completion, an average of 6 months. Cycle and treatment length vary by treatment phase.]
Eligibility criteria
Inclusion criteria
- Diagnosis of:
- Cohort 1: MM, based on IMWG criteria12, and currently requires treatment
- Cohort 2: Stage II or III TNBC, with definition per protocol Section 3.2.1 AND
- Plan for treatment, per their treating physician, or currently receiving their first cycle (see 3.3.3 for definition) of:
- Cohort 1: Dara-RVd for MM
- Cohort 2: A Keynote 522-based regimen of carboplatin, paclitaxel, and pembrolizumab given as the first phase of neoadjuvant treatment for TNBC.\*\*\*
- Participants are eligible even if the duration of carboplatin and paclitaxel goes beyond 4 cycles, or if the use of pembrolizumab, doxorubicin, and cyclophosphamide is not planned or is not certain, as long as neoadjuvant treatment starts with carboplatin-paclitaxel-pembrolizumab. This cohort will be referred to as "Keynote 522" for the remainder of the protocol.
AND
- Confirmed Duffy null phenotype
- Previous testing is acceptable if performed by a CLIA-approved test
AND
- Age >=18 years old
Exclusion criteria
- Inability to understand and the willingness to sign a written informed consent document
- ANC<500 within 7 days of planned start of Cycle 1 Day 1.
- Participants who have started treatment at the time of enrollment cannot have started Cycle 2 of therapy
- Participants in Cohort 2 (TNBC) cannot have received any of the pembrolizumab, doxorubicin, and cyclophosphamide portion of therapy
- Participants receiving any other investigational agents for any indication
- Another known condition or medicine with known impacts on neutrophil counts or neutrophil function
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Non-randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 1 center
- Dana-Farber Cancer Institute — Boston
Identifiers
NCT: NCT07341867 · 25-555