A Study of Alectinib and Duvelisib in People With Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma (ALK+ALCL)

A Phase I Study of Alectinib Plus Duvelisib in Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma (ALK+ ALCL)

The researchers are doing this study to see if alectinib in combination with duvelisib is a safe and effective time-limited treatment for people with relapsed or refractory ALK+ anaplastic large cell lymphoma (ALCL). The researchers will test different doses of the study drugs to find the highest doses that cause few or mild side effects in participants. Once they find this dose combination, they will test it in a new group of participants to learn how long the effect of the combination lasts after the end of treatment

Study Overview

• Status: Recruiting
• Conditions: Anaplastic Large Cell Lymphoma; Anaplastic Lymphoma Kinase
• Intervention / Treatment: Drug: Alectinib; Drug: Duvelisib

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Steven Horwitz, MD; Phone Number: 646-608-2680
• Study Contact Backup: Name: Robert Stuver, MD; Phone Number: 646-608-4308; Email: stuverr@mskcc.org

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Recruiting
      • Memorial Sloan Kettering Basking Ridge (LimitedProtocol Activities)
      • Contact: Robert Stuver, MD; Phone Number: 646-608-4308
    • Middletown, New Jersey, United States, 07748
      • Recruiting
      • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
      • Contact: Robert Stuver, MD; Phone Number: 646-608-4308
    • Montvale, New Jersey, United States, 07645
      • Recruiting
      • Memorial Sloan Kettering Bergen (Limited Protocol Activities)
      • Contact: Robert Stuver, MD; Phone Number: 646-608-4308
  • New York
    • Commack, New York, United States, 11725
      • Recruiting
      • Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)
      • Contact: Robert Stuver, MD; Phone Number: 646-608-4308
    • Harrison, New York, United States, 10604
      • Recruiting
      • Memorial Sloan Kettering Westchester (Limited Protocol Activities)
      • Contact: Robert Stuver, MD; Phone Number: 646-608-4308
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center (All Protocol Activities)
      • Contact: Robert Stuver, MD; Phone Number: 646-608-4308
    • Uniondale, New York, United States, 11553
      • Recruiting
      • Memorial Sloan Kettering Nassau (Limited Protocol Activities)
      • Contact: Robert Stuver, MD; Phone Number: 646-608-4308

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pathologically-confirmed diagnosis of ALK+ ALCL by WHO/ICC, classification procedures in use at the time of diagnosis. Note that ALK+ ALCL by definition expresses ALK, which is readily detectable on standard IHC. Confirmation through molecular sequencing of the specific ALK translocation and fusion partner is not necessary for enrollment.

• Relapsed or refractory disease after at least one line of prior systemic therapy.

  • NOTE: Prior systemic therapy must have included at least one cytotoxic chemotherapy agent.
  • NOTE: Prior treatment with an ALK inhibitor is allowed.
  • NOTE: Patients being treated with an ALK inhibitor immediately prior to enrollment are eligible. This includes patients on an ALK inhibitor who are in clinical remission at the time of enrollment, as long as the patient is not immediately planned for allogeneic transplant.
  • NOTE: If the last therapy was an ALK inhibitor, the patient must not have stopped the ALK inhibitor and maintained clinical remission (no relapse) with no intervening therapy for ≥ six months.
  • NOTE: Prior progression on ALK inhibitor is not specifically exclusionary though should be reviewed with the MSK Principal Investigator.
• Age ≥ 18 years at the time of enrollment
• ECOG performance status ≤ 2 at the time of enrollment.

• Laboratory criteria:

  • Absolute neutrophil count ≥ 1.0 K/mcL or ≥ 0.5 K/mcL if due to lymphoma (NOTE: growth factor is allowed).
  • Platelet count ≥ 75 K/uL.
  • Calculated creatinine clearance ≥ 60 mL/min by Cockcroft-Gault.
  • Total bilirubin ≤ 2x upper limit of normal (ULN) or ≤ 3x ULN if due to hepatobiliary involvement with lymphoma, or ≤ 3x ULN if history of Gilbert's disease.
  • Aspartate (AST) and alanine (ALT) aminotransferase ≤ 3 x ULN or ≤ 5x ULN if due to hepatobiliary involvement with lymphoma.
  • NOTE: Patients with AST and/or ALT > 3x ULN and total bilirubin > 2x ULN must be reviewed with the MSK Principal Investigator to determine eligibility.
  • NOTE: Patients must meet laboratory criteria prior to initiation of the alectinib lead-in cycle and prior to initiation of combination therapy with duvelisib
• Able to swallow pills.
• Able to take prophylactic medications against Pneumocystis jirovecii pneumonia (PJP)
• Women of reproductive potential must have a negative serum or urine β human chorionic gonadotropin (β-HCG) pregnancy test within 14 days before initiating therapy.
• Females of childbearing age must be on effective contraception per institutional standards during the treatment period and for 5 weeks after the last dose of the study drugs.
• Males must consistently use an effective contraception method per institutional standards during the treatment period and for 3 months following the last dose of the study drugs.

Exclusion Criteria:

• Prior allogeneic stem cell transplant within 6 months of starting treatment or patients with active graft versus host disease (GVHD).

  o NOTE: Prior allogeneic stem cell transplant may be allowed after discussion with MSK PI if no GVHD or immunosuppression is present at time of enrollment.

• Previous systemic anti-cancer therapy for ALK+ ALCL within 7 days of initiating study drug

  • NOTE: Systemic corticosteroids are allowed and must be tapered to 10 mg/day or less (prednisone equivalent) upon start of investigational treatment.
  • NOTE: Patients who have received localized radiotherapy as part of immediate prior therapy may be allowed to enroll with shorter washout period after discussion with the MSK Principal Investigator.
  • NOTE: Prior progression on ALK inhibitor is not specifically exclusionary though should be reviewed with the MSK Principal Investigatory.
• Ongoing use of immunosuppressant medications, including corticosteroids greater than 10 mg of prednisone or equivalent at the time of enrollment.
• Prior gastrointestinal condition or surgery that may, in the investigator's judgment, adversely affect drug absorption.

• Active viral infection with hepatitis B or hepatitis C. For hepatitis B, patients who are seropositive (hepatitis B core Ab positive) are permitted if HBV DNA is negative by PCR. For hepatitis C, patients who are seropositive (hepatitis C Ab positive) are eligible if HCV DNA is negative by PCR and curative therapy has been completed.

  o NOTE: Patients with HIV infection are permitted to enroll but are required to be on antiretroviral regimens that are in accordance with the current International AIDS Society guidelines on concurrent use with chemotherapy. Use of experimental antiretroviral agents or those containing zidovudine or ritonavir, cobicistat or similar potent CYP3 inhibitors are prohibited. In order to be eligible, patients taking zidovudine or ritonavir, or cobicistat or other CYP3 inhibitors must change to a different regimen 7 days prior to therapy initiation. Subjects must be on HAART for at least 12 weeks prior to therapy.

• Concurrent malignancy requiring active therapy within the last 2 years with the exception of basal cell or squamous cell carcinoma limited to the skin, carcinoma in situ of the cervix, breast or localized prostate cancer. Adjuvant or maintenance therapy to reduce the risk of recurrence or other malignancy is permissible after discussion with the Principal Investigator.
• Active cytomegalovirus (CMV) as defined by positive CMV PCR with clinical manifestations consistent with active CMV infection and requiring therapy. Carriers will be managed as per institutional guidelines.
• Patients should not be on CYP4503A inhibitors or inducers at the time of treatment initiation.
• Pregnant or breastfeeding women.
• Any serious or unstable medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing informed consent or, in the investigator's judgment, increase the risk to the patient associated with participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Alectinib and Duvelisib; All patients will receive a lead-in cycle (28 days) of alectinib. After this cycle, patients will undergo a PET/CT scan and safety assessment. Patients without progressive disease will continue on therapy. After the lead-in cycle of alectinib, in the absence of progressive disease as assessed by PET/CT scan, all patients will then receive two 28-day cycles of alectinib plus duvelisib. After two cycles of combination therapy, patients will undergo a response assessment.

Drug: Alectinib; All patients will receive a lead-in cycle (28 days) of alectinib.; Drug: Duvelisib; After the lead-in cycle of alectinib, in the absence of progressive disease as assessed by PET/CT scan, all patients will then receive two 28-day cycles of alectinib plus duvelisib.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the maximum tolerated dose (MTD)	of alectinib (A) + duvelisib (D) The MTD will be defined as the dose level at which the estimated dose-limiting toxicity (DLT) rate from the CRM model is closest to the target acceptable rate of 25%.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year relapse-free rate	in patients who achieve CR and stop treatment For PET/CT scan, a five-point scale for visually assessing response, referred to as the Deauville criteria, was developed by international experts in the field and will be utilized for grading of PET/CT response. The Lugano criteria will be applied to define complete response (CR), partial response (PR), stable disease (SD), and progression of disease (PD).	1 year

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Genentech, Inc.; Secura Bio, Inc.
• Investigators: Principal Investigator: Robert Stuver, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2025
• Primary Completion (Estimated): August 8, 2031
• Study Completion (Estimated): August 8, 2031

Study Registration Dates

• First Submitted: May 23, 2025
• First Submitted That Met QC Criteria: May 23, 2025
• First Posted (Actual): June 3, 2025

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Duvelisib; Alectinib; 25-056
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Hemic and Lymphatic Diseases; Lymphoma, Large-Cell, Anaplastic; Tyrosine Kinase Inhibitors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; duvelisib; alectinib
• Other Study ID Numbers: 25-056

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No