Chemoimmunotherapy for Anaplastic Large Cell Lymphoma

(ACCELERATE Trial)

Overseen By Lauren Harrison, RN, MSN

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: New York Medical College

Disqualifiers: ALK-negative ALCL, Leptomeningeal disease, Down syndrome, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for ALK+ Anaplastic Large Cell Lymphoma (ALCL), particularly in cases where the cancer has returned or hasn't responded to initial treatment. Researchers are testing a combination of the FDA-approved immunotherapy drug Nivolumab with chemotherapy to determine if it can improve survival rates. Participants will also receive stem cell transplants from donors. This trial is suitable for children, adolescents, and young adults with ALK+ ALCL who have certain characteristics, such as a relapse occurring after one year from initial diagnosis or specific cell markers in their cancer. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that Nivolumab offers promising safety results for people with relapsed or refractory ALK+ anaplastic large cell lymphoma (ALCL). Patients treated with Nivolumab achieved a 3-year overall survival rate of 90%, indicating it is generally well-tolerated. However, like all treatments, it can cause side effects such as tiredness, skin rash, and diarrhea, which are often manageable.

Vinblastine, when used alone, is part of the standard care for children with late relapse of ALCL. It is generally considered safe, although some side effects have been noted when combined with other treatments.

Brentuximab vedotin, another related treatment, has demonstrated high remission rates in studies with ALCL, with overall response rates between 75% and 86%. It is usually well-tolerated, but some patients may experience side effects like nerve damage.

Overall, these treatments have shown relative safety in previous studies. However, participating in clinical trials should always involve discussing potential risks and benefits with healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about nivolumab for treating Anaplastic Large Cell Lymphoma (ALCL) because it works differently from the standard chemotherapies and targeted therapies typically used for this condition. Nivolumab is an immune checkpoint inhibitor that boosts the immune system by blocking the PD-1 pathway, which cancer cells often exploit to hide from immune attacks. This mechanism allows the body's own defenses to better recognize and fight the cancer cells. Unlike traditional treatments, which directly target the cancer cells, nivolumab enhances the body's natural ability to combat the tumor, potentially leading to more durable responses. This novel approach could offer hope for patients, especially those who have experienced relapses or whose disease has progressed despite conventional treatments.

What evidence suggests that this trial's treatments could be effective for ALK+ Anaplastic Large Cell Lymphoma?

Research has shown that Nivolumab, a type of immunotherapy, holds potential for treating relapsed or hard-to-treat ALK-positive anaplastic large cell lymphoma (ALCL). In this trial, some participants will receive Nivolumab. Studies have found that it results in a five-year survival rate of 91%, suggesting it may help patients remain in remission longer. While traditional chemotherapy is often used, Nivolumab enhances the immune system's ability to fight cancer. These encouraging results offer hope for improving survival rates in high-risk patients. ^{4 5 6 7 8}

Who Is on the Research Team?

Mitchell S Cairo, MD

Principal Investigator

New York Medical College

Are You a Good Fit for This Trial?

This trial is for children, adolescents, and young adults with high-risk ALK+ Anaplastic Large Cell Lymphoma (ALCL) that has come back or hasn't responded to treatment. Participants must meet certain health criteria to be eligible.

Inclusion Criteria

I weigh at least 10 kilograms.

My lymphoma is ALK-positive and has not responded to treatment.

I am mostly able to take care of myself.

Exclusion Criteria

My lymphoma is ALK-negative.

Lactating females unless they have agreed not to breastfeed their infants

Patients with Down syndrome

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive Nivolumab (NIVO) combined with chemotherapy based on risk status to achieve the best response possible

12 weeks

Consolidation Treatment

Participants receive lower doses of chemoimmunotherapy and allogeneic stem cell transplantation

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Brentuximab vedotin
• Nivolumab
• Vinblastine

Trial Overview The study tests a combination of Nivolumab (a checkpoint blockade immunotherapy) with chemotherapy tailored to the patient's risk status, followed by lower doses of chemoimmunotherapy and allogeneic stem cell transplantation.

How Is the Trial Designed?

Group I: Low-risk ALK+ ALCL Experimental Treatment 1 Intervention

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).

Group II: High Risk ALK+ ALCL (with prior BV) Experimental Treatment 3 Interventions

* 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)

Group III: High Risk ALK+ ALCL (BV Naive) Experimental Treatment 3 Interventions

* 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)

Who Is Running the Clinical Trial?

New York Medical College

Lead Sponsor

Trials

73

Recruited

8,700+

Helen DeVos Children's Hospital

Collaborator

Trials

11

Recruited

7,400+

University of Utah

Collaborator

Trials

1,169

Recruited

1,623,000+

University of North Carolina

Collaborator

Trials

174

Recruited

1,457,000+

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

Children's Hospital of Orange County

Collaborator

Trials

38

Recruited

5,700+

Medical College of Wisconsin

Collaborator

Trials

645

Recruited

1,180,000+

University of Alabama at Birmingham

Collaborator

Trials

1,677

Recruited

2,458,000+

Nationwide Children's Hospital

Collaborator

Trials

354

Recruited

5,228,000+

Memorial Sloan Kettering Cancer Center

Collaborator

Trials

1,998

Recruited

602,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5746164/

Five-year results of brentuximab vedotin in patients with ... This pivotal phase 2 study evaluated the safety and efficacy of brentuximab vedotin in patients with relapsed or refractory (R/R) systemic anaplastic large cell ...

2. nature.com nature.com/articles/s41408-025-01329-2

subgroup analysis of the ECHELON-2 study at 5 years ... Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study. J ...

3. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1494384/full

Real-world experiences with brentuximab vedotion-based ... Background: Brentuximab vedotin (BV) has demonstrated high remission rates in clinical trials for systemic anaplastic large cell lymphoma (sALCL) ...

4. ashpublications.org ashpublications.org/blood/article-abstract/130/25/2709/36882

Five-year results of brentuximab vedotin in patients with ... Patients with R/R ALCL who achieved CR with brentuximab vedotin had 79% OS and 57% PFS at 5 years, with median response duration not reached.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0959804917310778

Long-term outcomes of adults with first-relapsed/refractory ... Most adults with first-R/R ALCL have poor outcomes, with no significant differences between patients with ALK(+) or ALK(−) disease.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3627331/

Safety and efficacy of brentuximab vedotin in patients with ... In phase II studies, brentuximab vedotin induced overall response rates of 75% and 86% in relapsed or refractory Hodgkin lymphoma and anaplastic large cell ...

7. ashpublications.org ashpublications.org/blood/article/130/25/2709/36882/Five-year-results-of-brentuximab-vedotin-in

Five-year results of brentuximab vedotin in patients with ... Patients with R/R ALCL who achieved CR with brentuximab vedotin had 79% OS and 57% PFS at 5 years, with median response duration not reached ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03113500

Study Details | NCT03113500 | Brentuximab Vedotin and ... This phase II trial studies the side effects and how well brentuximab vedotin and combination chemotherapy work in treating patients with CD30-positive ...