Systemic Anti-Cancer Therapy Dose Modifications for Individuals With Duffy Null Phenotype

Andrew Hantel, MD

Status and phase: Begins enrollment in 3 months; Phase 1

Conditions: Multiple Myeloma; Duffy Blood Group, Chemokine Receptor Gene C.-67T>C; Duffy Blood Group, Chemokine Receptor Gene Mutation; Triple Negative Breast Cancer

Treatments: Drug: Carboplatin; Drug: Dexamethasone; Drug: Pembrolizumab; Drug: Daratumumab; Drug: Paclitaxel; Drug: Doxorubicin; Drug: LENALIDOMIDE; Drug: Cyclophosphamide; Drug: Bortezomib

Study type: Interventional

Funder types: Other

Identifiers

NCT07341867

25-555

Details and patient eligibility

About

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

Full 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.

Enrollment: 90 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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90 participants in 2 patient groups

Arm A: Multiple myeloma (MM)

Experimental group

Description:

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

Treatment:

Drug: Bortezomib

Drug: LENALIDOMIDE

Drug: Daratumumab

Drug: Dexamethasone

Arm B: Triple-Neg Breast Cancer

Experimental group

Description:

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

Treatment:

Drug: Cyclophosphamide

Drug: Doxorubicin

Drug: Pembrolizumab

Drug: Paclitaxel

Drug: Carboplatin