Chemoimmunotherapy for ALK+ Relapsed/Refractory ALCL

NCT07013565 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: NYMC 623
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Children, adolescents, and young adults (CAYA) with relapsed/refractory (R/R) high-risk ALK+ Anaplastic Large Cell Lymphoma (ALCL) have a low incidence of overall survival. This clinical trial will investigate if a new FDA approved medication called Nivolumab (NIVO) (which is a checkpoint blockade immunotherapy) combined with chemotherapy based on the patients risk status to get the patient into the best response possible. Then patients will receive lower doses of chemoimmunotherapy and allogeneic stem cell transplantation (stem cells from another person). The investigators this this new treatment will improve survival rates in this high-risk population of patients.

Conditions

Anaplastic Large Cell Lymphoma, ALK-Positive

Keywords

ALCL; Relapsed ALCL

Outcome Measures

Primary Outcomes (5)

• To determine the incidence of adverse events (safety) of NIVO and Vinblastine (VBL) in CAYA with high-risk R/R ALK+ ALCL with prior exposure to Brentuximab vedotin (BV)

  adverse events possible probably or definitely related to NIVO will be reported.

  1 year

• To determine the overall response rate of NIVO and Vinblastine (VBL) in CAYA with high-risk R/R ALK+ ALCL with prior exposure to Brentuximab vedotin (BV).

  Patient will have disease assessments to determine best response to therapy with NIVO and Vinblastine

  1 year

• To determine the safety of NIVO and BV in CAYA with high-risk R/R ALK+ ALCL who have never received BV.

  adverse events probably or definitely related to NIVO will be collected.

  1 year

• To determine the overall response rate to NIVO and BV in CAYA with high-risk R/R ALK+ ALCL who have never received BV.

  disease assessments will be performed to determine best response post therapy

  1 year

• To significantly improve the 1 year EFS in CAYA with high-risk ALCL who received NIVO risk-adapted combining immunotherapy with re-induction followed by RTC and AlloHSCT compared to historical controls.

  Events for EFS the first year will be reported and are defined as disease relapse, disease progression or toxic death.

  1 year

Study Arms (3)

Low-risk ALK+ ALCL

EXPERIMENTAL

Low risk patients include any patient with FIRST RELAPSE \> ONE YEAR from initial diagnosis of de novo ALK+ ALCL,Common histology, CD3 negative, Minimum disseminated disease (MDD) negative at de novo diagnosis (if MDD known), AND No prior exposure to vinblastine (VBL).

Drug: Vinblastine (Velban)

High Risk ALK+ ALCL (BV Naive)

EXPERIMENTAL

* Any patient with RELAPSED OR PROGRESSIVE DISEASE ONE YEAR from initial diagnosis of de novo ALK+ ALCL, * Small cell/histiocytic histology, * CD3 positive (homogeneous staining of CD3 positive T-cells) * Second or later relapse, * Induction failure during initial treatment for de novo ALK+ ALCL, OR * Minimal disseminated disease (MDD) positive at de novo diagnosis (if MDD known)

Drug: Vinblastine (Velban); Drug: Brentuximab vedotin (Adcetris); Drug: Nivolumab (Opdivo)

High Risk ALK+ ALCL (with prior BV)

EXPERIMENTAL

* Any patient with RELAPSED OR PROGRESSIVE DISEASE ONE YEAR from initial diagnosis of de novo ALK+ ALCL, * Small cell/histiocytic histology, * CD3 positive (homogeneous staining of CD3 positive T-cells) * Second or later relapse, * Induction failure during initial treatment for de novo ALK+ ALCL, OR * Minimal disseminated disease (MDD) positive at de novo diagnosis (if MDD known)

Drug: Vinblastine (Velban); Drug: Brentuximab vedotin (Adcetris); Drug: Nivolumab (Opdivo)

Interventions

Vinblastine (Velban) DRUG

Low risk cohort patients will receive 2 cycles of Induction therapy with single-drug vinBLAStine (VBL), then undergo disease assessment. If complete remission (CR) and MRD -, LR patients will continue single-drug VBL for a total of 24 months (if absent disease progression or unacceptable toxicity).

High Risk ALK+ ALCL (BV Naive); High Risk ALK+ ALCL (with prior BV); Low-risk ALK+ ALCL

Brentuximab vedotin (Adcetris) DRUG

HR cohort patients with no previous exposure to BV will receive 2 cycles of Induction therapy with BV and NIVO \[BV + NIVO\] one every 21 days, then undergo disease assessment. Patients in CR will proceed with consolidation with RTC allogeneic SCT (SCT)\*. If patient has any response other than CR and MRD-, they will receive 2 cycles of BV, VBL, and NIVO \[BV + VBL + NIVO\] once every 21 days

Also known as: Nivolumab

High Risk ALK+ ALCL (BV Naive); High Risk ALK+ ALCL (with prior BV)

Nivolumab (Opdivo) DRUG

High risk cohort patients with previous exposure to Brentuximab vedotin (BV) will receive 2 cycles of Induction therapy with VBL and NIVO \[VBL + NIVO\] on day 1 and 15, then undergo disease assessment. If response is not CR, or patient has PR/SD/PD, patient will receive \[BV+VBL+NIVO\] and subsequent therapy as defined for the HR2 cohort.

Also known as: brentuximab vedodin, Vinblastine

High Risk ALK+ ALCL (BV Naive); High Risk ALK+ ALCL (with prior BV)

Eligibility Criteria

• Age: 1 Year - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must weigh ≥10 kilograms at the time of study enrollment.
• Patients with relapsed or refractory histologically or cytologically proven ALK-positive anaplastic large cell lymphoma meeting Low or High Risk Criteria:
• Low Risk Cohort (LR cohort):
• Any patient with FIRST RELAPSE \> ONE YEAR from initial diagnosis of de novo ALK+ ALCL,
• Common histology,
• CD3 negative, AND
• No prior exposure to vinblastine (VBL).
• High-Risk Cohort (HR cohort):
• Any patient with RELAPSED OR PROGRESSIVE DISEASE less than ONE YEAR from initial diagnosis of de novo ALK+ ALCL,
• Small cell/histiocytic histology,
• CD3 positive (homogeneous staining of CD3 positive T-cells)
• Patients must have adequate organ function.
• Patients must have performance status 60 or above.

You may not qualify if:

• ALK-NEGATIVE anaplastic large cell lymphoma.
• Patients with active leptomeningeal disease (lymphoma cells in CSF).
• Previous treatment with vinblastine (only in patients in the LR cohort).
• Female patients who are pregnant. Pregnancy tests must be obtained in girls who are post menarche.
• Lactating females unless they have agreed not to breastfeed their infants.
• Patients with Down syndrome.
• Any patient with uncontrolled infection prior to study entry.
• Any patient known to have primary or acquired immunodeficiency and/or prior solid organ transplant.

Sponsors & Collaborators

• New York Medical College: lead
• University of Alabama at Birmingham: collaborator
• Helen DeVos Children's Hospital: collaborator
• Nationwide Children's Hospital: collaborator
• Memorial Sloan Kettering Cancer Center: collaborator
• University of Utah: collaborator
• Ohio State University: collaborator
• University of North Carolina: collaborator
• Children's Hospital of Philadelphia: collaborator
• Medical College of Wisconsin: collaborator
• Children's Hospital of Orange County: collaborator

Study Sites (1)

New York Medical College

Valhalla, New York, 10595, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large-Cell, Anaplastic

Interventions

Vinblastine; Brentuximab Vedotin; Nivolumab

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Study Officials

• Mitchell S Cairo, MD

  New York Medical College

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mitchell S Cairo, MD

CONTACT

914-594-2150; mitchell_cairo@nymc.edu

Lauren Harrison, RN, MSN

CONTACT

617-285-2844; lauren_harrison@nymc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2025
• First Posted: June 10, 2025
• Study Start: August 7, 2025
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2030
• Last Updated: May 20, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)