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

NCT07341867 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 25-555
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

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

Keywords

Duffy Null Phenotype; Multiple Myeloma; Triple Negative Breast Cancer; Dosing guidelines

Outcome Measures

Primary Outcomes (2)

• Avoided or reduced systemic anticancer therapy (SACT) modifications per cycle

  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.

  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

  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.

  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 Outcomes (3)

• 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.

Study Arms (2)

Arm A: Multiple myeloma (MM)

EXPERIMENTAL

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

Drug: Dexamethasone; Drug: Bortezomib; Drug: LENALIDOMIDE; Drug: Daratumumab

Arm B: Triple-Neg Breast Cancer

EXPERIMENTAL

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

Drug: Carboplatin; Drug: Paclitaxel; Drug: Pembrolizumab; Drug: Cyclophosphamide; Drug: Doxorubicin

Interventions

Bortezomib DRUG

Intravenous infusion

Also known as: Velcade

Arm A: Multiple myeloma (MM)

LENALIDOMIDE DRUG

Tablet, taken orally

Also known as: Revlimid

Arm A: Multiple myeloma (MM)

Daratumumab DRUG

Intravenous infusion

Also known as: Darzalex, Darzalex Faspro

Arm A: Multiple myeloma (MM)

Carboplatin DRUG

Intravenous infusion

Also known as: Paraplatin

Arm B: Triple-Neg Breast Cancer

Paclitaxel DRUG

Intravenous infusion

Also known as: Taxol

Arm B: Triple-Neg Breast Cancer

Pembrolizumab DRUG

Intravenous infusion

Also known as: Keytruda, Keytruda Qlex

Arm B: Triple-Neg Breast Cancer

Cyclophosphamide DRUG

Intravenous infusion

Also known as: Cytoxan

Arm B: Triple-Neg Breast Cancer

Doxorubicin DRUG

Intravenous infusion

Also known as: Adriamycin, Rubex, Doxorubicin hydrochloride (HCl), Hydroxydaunorubicin, ADM

Arm B: Triple-Neg Breast Cancer

Dexamethasone DRUG

Tablet, taken orally

Also known as: Decadron, Dexamethasone Intensol, Dexasone, Solurex, Baycadron

Arm A: Multiple myeloma (MM)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Andrew Hantel, MD: lead

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Triple Negative Breast Neoplasms

Interventions

Dexamethasone; Calcium Dobesilate; Bortezomib; Lenalidomide; daratumumab; Carboplatin; Paclitaxel; pembrolizumab; Cyclophosphamide; Doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Breast Neoplasms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coordination Complexes; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Andrew Hantel, MD

  MD

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrew Hantel, MD

CONTACT

617-582-9394; andrew_hantel@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: December 15, 2025
• First Posted: January 14, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2029
• Last Updated: July 17, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (1)