RECRUITING

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

Conditions

Anaplastic Lymphoma Kinase Anaplastic Large Cell Lymphoma Alectinib Duvelisib 25-056

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

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

Quick Facts

Study Start:2025-08-08

Study Completion:2031-08-08

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT07001384

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

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

Inclusion Criteria

Exclusion 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.

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

Contacts and Locations

Study Contact

Robert Stuver, MD

CONTACT

646-608-4308

stuverr@mskcc.org

Steven Horwitz, MD

CONTACT

646-608-2680

Principal Investigator

Robert Stuver, MD

PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Study Locations (Sites)

Memorial Sloan Kettering Basking Ridge (LimitedProtocol Activities)

Basking Ridge, New Jersey, 07920

United States

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748

United States

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645

United States

Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)

Commack, New York, 11725

United States

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604

United States

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065

United States

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553

United States

Collaborators and Investigators

Sponsor: Memorial Sloan Kettering Cancer Center

Robert Stuver, MD, PRINCIPAL_INVESTIGATOR, Memorial Sloan Kettering Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-08-08

Study Completion Date2031-08-08

Study Record Updates

Study Start Date2025-08-08

Study Completion Date2031-08-08

Terms related to this study

Keywords Provided by Researchers

Alectinib
Duvelisib
25-056

Additional Relevant MeSH Terms

Anaplastic Lymphoma Kinase
Anaplastic Large Cell Lymphoma