A Pilot Study of Duffy Null-Specific Dose Modifications for Individuals With Duffy Null Phenotype Receiving Standard of Care Systemic Anti-Cancer Therapies
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Avoided or reduced systemic anticancer therapy (SACT) modifications per cycle
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •Confirmed Duffy null phenotype
- •Previous testing is acceptable if performed by a CLIA-approved test
- •Age >=18 years old
排除标准
- •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
- •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
研究组 & 干预措施
Arm A: Multiple myeloma (MM)
Participants with Multiple Myeloma and identified Duffy Null phenotype will receive standard of care (Dara-RVD) per institutional protocol with dosage adjustments per Duffy-Null guidance.
Study treatment cycle lasts 28 days
- dexamethasone 1X daily on days 1, 2, 8, 9, 15, 16, 22, 23 for 6 cycles
- lenalidomide 1x daily on days 1-21 for 6 cycles
- bortezomib 1x weekly for 2 cycles
- daratumumab 1x weekly up to 2 cycles, then every 14 days for 4 more cycles
干预措施: Daratumumab (Drug)
Arm B: Triple-Neg Breast Cancer
Participants with Triple Negative Breast Cancer and identified Duffy Null phenotype will receive standard of care (Keynote-522) per institutional protocol with dosage adjustments per Duffy-Null guidance
Study treatment cycle lasts 21 days
- Pembrolizumab 1x every 21 days on day 1 for cycles 1-4
- Paclitaxel 1x weekly on D1, 8, and 15 for cycles 1-4
- Carboplatin 1x weekly on D1, 8, and 15 for cycles 1-4
- Doxorubicin 1x every 14 days for cycles 5-8
- Cyclophosphamide 1x every 14 days for cycles 5-8
- Pembrolizumab 1x every 21 days on day 1 for cycles 5-8
干预措施: Carboplatin (Drug)
Arm B: Triple-Neg Breast Cancer
Participants with Triple Negative Breast Cancer and identified Duffy Null phenotype will receive standard of care (Keynote-522) per institutional protocol with dosage adjustments per Duffy-Null guidance
Study treatment cycle lasts 21 days
- Pembrolizumab 1x every 21 days on day 1 for cycles 1-4
- Paclitaxel 1x weekly on D1, 8, and 15 for cycles 1-4
- Carboplatin 1x weekly on D1, 8, and 15 for cycles 1-4
- Doxorubicin 1x every 14 days for cycles 5-8
- Cyclophosphamide 1x every 14 days for cycles 5-8
- Pembrolizumab 1x every 21 days on day 1 for cycles 5-8
干预措施: Doxorubicin (Drug)
Arm B: Triple-Neg Breast Cancer
Participants with Triple Negative Breast Cancer and identified Duffy Null phenotype will receive standard of care (Keynote-522) per institutional protocol with dosage adjustments per Duffy-Null guidance
Study treatment cycle lasts 21 days
- Pembrolizumab 1x every 21 days on day 1 for cycles 1-4
- Paclitaxel 1x weekly on D1, 8, and 15 for cycles 1-4
- Carboplatin 1x weekly on D1, 8, and 15 for cycles 1-4
- Doxorubicin 1x every 14 days for cycles 5-8
- Cyclophosphamide 1x every 14 days for cycles 5-8
- Pembrolizumab 1x every 21 days on day 1 for cycles 5-8
干预措施: Paclitaxel (Drug)
Arm B: Triple-Neg Breast Cancer
Participants with Triple Negative Breast Cancer and identified Duffy Null phenotype will receive standard of care (Keynote-522) per institutional protocol with dosage adjustments per Duffy-Null guidance
Study treatment cycle lasts 21 days
- Pembrolizumab 1x every 21 days on day 1 for cycles 1-4
- Paclitaxel 1x weekly on D1, 8, and 15 for cycles 1-4
- Carboplatin 1x weekly on D1, 8, and 15 for cycles 1-4
- Doxorubicin 1x every 14 days for cycles 5-8
- Cyclophosphamide 1x every 14 days for cycles 5-8
- Pembrolizumab 1x every 21 days on day 1 for cycles 5-8
干预措施: Pembrolizumab (Drug)
Arm B: Triple-Neg Breast Cancer
Participants with Triple Negative Breast Cancer and identified Duffy Null phenotype will receive standard of care (Keynote-522) per institutional protocol with dosage adjustments per Duffy-Null guidance
Study treatment cycle lasts 21 days
- Pembrolizumab 1x every 21 days on day 1 for cycles 1-4
- Paclitaxel 1x weekly on D1, 8, and 15 for cycles 1-4
- Carboplatin 1x weekly on D1, 8, and 15 for cycles 1-4
- Doxorubicin 1x every 14 days for cycles 5-8
- Cyclophosphamide 1x every 14 days for cycles 5-8
- Pembrolizumab 1x every 21 days on day 1 for cycles 5-8
干预措施: Cyclophosphamide (Drug)
Arm A: Multiple myeloma (MM)
Participants with Multiple Myeloma and identified Duffy Null phenotype will receive standard of care (Dara-RVD) per institutional protocol with dosage adjustments per Duffy-Null guidance.
Study treatment cycle lasts 28 days
- dexamethasone 1X daily on days 1, 2, 8, 9, 15, 16, 22, 23 for 6 cycles
- lenalidomide 1x daily on days 1-21 for 6 cycles
- bortezomib 1x weekly for 2 cycles
- daratumumab 1x weekly up to 2 cycles, then every 14 days for 4 more cycles
干预措施: Bortezomib (Drug)
Arm A: Multiple myeloma (MM)
Participants with Multiple Myeloma and identified Duffy Null phenotype will receive standard of care (Dara-RVD) per institutional protocol with dosage adjustments per Duffy-Null guidance.
Study treatment cycle lasts 28 days
- dexamethasone 1X daily on days 1, 2, 8, 9, 15, 16, 22, 23 for 6 cycles
- lenalidomide 1x daily on days 1-21 for 6 cycles
- bortezomib 1x weekly for 2 cycles
- daratumumab 1x weekly up to 2 cycles, then every 14 days for 4 more cycles
干预措施: LENALIDOMIDE (Drug)
Arm A: Multiple myeloma (MM)
Participants with Multiple Myeloma and identified Duffy Null phenotype will receive standard of care (Dara-RVD) per institutional protocol with dosage adjustments per Duffy-Null guidance.
Study treatment cycle lasts 28 days
- dexamethasone 1X daily on days 1, 2, 8, 9, 15, 16, 22, 23 for 6 cycles
- lenalidomide 1x daily on days 1-21 for 6 cycles
- bortezomib 1x weekly for 2 cycles
- daratumumab 1x weekly up to 2 cycles, then every 14 days for 4 more cycles
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Avoided or reduced systemic anticancer therapy (SACT) modifications per cycle
时间窗: 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
An ANC-related avoided or reduced SACT change is defined as an instance of no change in SACT dosing (by avoiding a dose hold, dose level change, or drug discontinuation) OR an instance of reduction in the SACT dose modification (through earlier resumption of therapy with or without avoidance of a dose modification in a subsequent cycle) using this study's Duffy null-specific parameters for ANC dose modifications compared to the dose modification that would have occurred according to the parameters used in PERSEUS (Dara-RVD) or Keynote 522 trials. For the primary outcome measure, an ANC-related avoided or reduced SACT change is measured on a per-cycle basis as a binary outcome.
Overall cumulative incidence of neutropenic fever
时间窗: 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)).
Neutropenic fever is defined using modified CTCAE criteria. Grade 3 being defined as "ANC\<500/uL with a single temperature of \>38.3 C or a sustained temperature of \>38 for more than one hour"; and Grade 4 defined as "Life-threatening consequences; urgent intervention indicated". The cumulative incidence will be calculated as the number of participants with at least one documented occurrence of neutropenic fever, over the total number of participants enrolled.
次要结局
- Avoided or reduced systemic anticancer therapy (SACT) modifications per ANC check (i.e. per week)(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(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)(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.)
研究者
Andrew Hantel, MD
Sponsor Investigator
Dana-Farber Cancer Institute