Fludarabine for Acute Lymphoblastic Leukemia

Recruiting at 6 trial locations

Overseen By Kevin Curran, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Fludarabine, Cyclophosphamide, Tisagenlecleucel

Disqualifiers: Infection, Pregnancy, Consent issues, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

130 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a specific method of administering the chemotherapy drug fludarabine benefits individuals with relapsed or hard-to-treat B-cell acute lymphoblastic leukemia (B-ALL) undergoing CAR T-cell therapy. Researchers will compare two methods of administering fludarabine to identify which is more effective and has fewer side effects. Individuals with B-ALL who are scheduled to receive commercial CAR T-cell therapy and weigh over 20 pounds may qualify for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications for the trial?

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?

In a previous study, researchers found that patients generally tolerate fludarabine well. Evidence shows that adjusting the dose based on age and other factors can improve outcomes without increasing risk. Studies have noted good results with manageable side effects for the standard treatment plan when used for similar conditions.

For the targeted treatment plan, research suggests that adjusting fludarabine dosing to reach a specific drug level is promising. It has not shown an increase in severe side effects compared to standard dosing methods. Overall, both treatment plans offer a balance between effectiveness and safety, focusing on reducing side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a targeted approach to fighting acute lymphoblastic leukemia (ALL). While standard treatments typically involve chemotherapy drugs like vincristine, prednisone, and doxorubicin, these investigational regimens focus on using fludarabine in combination with CAR-T cell therapy. The standard regimen uses a fixed dose of fludarabine, but the experimental regimen adjusts the dosage based on the patient's pharmacokinetics, aiming for a precise drug exposure level. This personalized dosing strategy could potentially improve treatment effectiveness and reduce side effects, offering new hope for patients battling ALL.

What evidence suggests that this trial's treatments could be effective for B-cell acute lymphoblastic leukemia?

Research has shown that the right amount of fludarabine can improve outcomes after CAR T-cell therapy for people with B-cell acute lymphoblastic leukemia (B-ALL). In this trial, participants will receive either a standard or targeted fludarabine regimen, both followed by CAR-T therapy. One study found that higher amounts of fludarabine can reduce the risk of cancer recurrence and help patients remain cancer-free longer. These benefits have appeared with both standard and personalized dosing methods. Personalized dosing aims to achieve a specific drug level in the body, potentially increasing effectiveness. Both methods show promise, with personalized dosing tailored to each patient's needs, offering better control over the treatment process. ^{2 3 4 6 7}

Who Is on the Research Team?

Kevin Curran, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for children and young adults with B-cell Acute Lymphoblastic Leukemia (B-ALL) or Burkitt Lymphoma who have relapsed or are not responding to treatment. They should be eligible for CAR T-cell therapy. Specific inclusion and exclusion criteria details were not provided.

Inclusion Criteria

Pulmonary: Oxygen saturation as recorded by pulse oximetry of ≥ 90% on room air

Adequate performance status:

Willing to participate as research subject and provide written informed consent from parents/legal representative, patient, and age-appropriate assent as appropriate before any study specific screening procedures are conducted, according to local, regional or national law and legislation.

Exclusion Criteria

Pregnant or lactating women

Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to the study drugs, or drugs chemically related to study treatment or excipients that contraindicate their participation, including fludarabine, cyclophosphamide and tisagenlecleucel

Patient/parent/guardian unable to give informed consent or unable to comply with the treatment protocol

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion Chemotherapy

Participants receive fludarabine as part of lymphodepletion chemotherapy prior to CAR T-cell therapy. Standard regimen: Fludarabine 30 mg/m2/dose x 4 doses on days -6 to -3. Targeted regimen: Fludarabine 40 mg/m2/dose x 2 doses on days -6 and -5, with adjusted doses on days -4 and -3 based on PK analysis.

4 days

CAR T-cell Therapy

Participants receive tisagenlecleucel CAR T-cell therapy following lymphodepletion chemotherapy.

1 day

Follow-up

Participants are monitored for safety and effectiveness after CAR T-cell therapy, including assessment of event-free survival and quality of life.

28 days

What Are the Treatments Tested in This Trial?

Interventions

• CAR-T
• Cyclophosphamide
• Fludarabine

Trial Overview The study tests if PK-targeted fludarabine dosing can better prepare patients for CAR T-cell therapy compared to standard dosing, in terms of effectiveness and practicality. It also examines the impact on side effects and quality of life through questionnaires.

How Is the Trial Designed?

Group I: Targeted fludarabine regimen followed by CAR-T Experimental Treatment 3 Interventions

Fludarabine 40 mg/m2/dose x 2 doses on days -6 and -5 (or -7 and -6), with doses on days -4 and -3 (or -5 and -4, if starting lymphodepletion on day -7) adjusted based on PK analysis to target a cumulative area under the curve (AUC) of 18 mg\*h/L (range 17.5-18.5mg\*h/L

Group II: Standard Fludarabine regimen followed by CAR-T Active Control 3 Interventions

Fludarabine 30 mg/m2/dose x 4 doses on days -6 to -3 (or -7 to -4)

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Princess Maxima Center for Pediatric Oncology

Collaborator

Trials

19

Recruited

11,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9006295/

Optimal fludarabine lymphodepletion is associated with ... Optimal fludarabine lymphodepletion is associated with improved outcomes after CAR T-cell therapy · Key Points. Optimal fludarabine exposure in those with ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01991457?tab=results

Study Results | Fludarabine / Total Body Irradiation ... It identifies the role of the intervention that participants receive. Types of arms include experimental arm, active comparator arm, placebo comparator arm, ...

3. ashpublications.org ashpublications.org/bloodadvances/article/9/18/4676/546047/Age-adjusted-dosing-of-fludarabine-for

Age-adjusted dosing of fludarabine for lymphodepletion in ... Higher FLU systemic exposure is associated with lower relapse risk and improved leukemia-free survival in pediatric patients with acute ...

4. astctjournal.org astctjournal.org/article/S1083-8791(20)30227-5/fulltext

Long-Term Outcomes of Allogeneic Hematopoietic Cell ... This regimen had favorable outcomes in adult ALL patients with Ph+ status. Abstract. Acute lymphoblastic leukemia (ALL) is associated with poor survival in ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S247395292500388X

Age-adjusted dosing of fludarabine for lymphodepletion in ... Higher FLU systemic exposure is associated with lower relapse risk and improved leukemia-free survival in pediatric patients with acute ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8822504/

Long-Term Outcomes of Allogeneic Hematopoietic Cell ... RIC HCT with FluMel conditioning and T/S GVHD prophylaxis was associated with favorable outcomes in patients with Ph+ ALL and should be considered as a viable ...

7. astctjournal.org astctjournal.org/article/S1083-8791(20)30227-5/pdf

Long-Term Outcomes of Allogeneic Hematopoietic Cell ... Here, we report on outcomes of a consecutive case series of 72 patients with ALL who under- went RIC alloHCT while in CR at COH between 2005 and 2018 using our ...