Methadone for Pain Management in Stem Cell Transplants

(MATCH Trial)

Overseen By Kiley Poppino

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Texas Southwestern Medical Center

Must be taking: Opioids

Must not be taking: Chronic pain medications

Disqualifiers: QT prolongation, Neurological, Psychiatric, 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

Duration: 6-8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding methadone, a pain reliever, to the usual morphine treatment reduces pain from mouth sores caused by chemotherapy during stem cell transplants. Researchers hope methadone will offer better pain control while waiting for new donor cells to grow and heal the mouth. Children and teens aged 6-18 undergoing a stem cell transplant and experiencing painful mouth sores from chemotherapy may be suitable participants. As a Phase 3 trial, this treatment is in the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in pain management.

Will I have to stop taking my current medications?

The trial requires that participants not be on chronic pain medications or have received more than 30 days of continuous opioids in the past month. If you are currently taking such medications, you may need to stop them to participate.

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

Research has shown that methadone is generally well-tolerated for managing pain. Studies have found it effective in controlling pain with fewer side effects than some other opioids. However, like any medication, it can cause side effects. Common ones include nausea, dizziness, or drowsiness. More serious side effects are rare but can include changes in heart rhythm or trouble breathing.

The FDA has approved methadone for other uses, such as treating opioid addiction and managing severe pain. This approval indicates a certain level of safety when used under a doctor's care.

Clinical studies have demonstrated that methadone can be safely used with other pain medications. This combination can be helpful because methadone works differently in the brain than drugs like morphine, possibly offering better pain relief. Overall, methadone's safety is well-documented, but participants should always be monitored for any side effects.

Why are researchers excited about this study treatment for pain management in stem cell transplants?

Unlike the standard of care for pain management in stem cell transplant patients, which typically involves opioids like morphine or hydromorphone, methadone offers a unique approach. Methadone is administered intravenously every 8 hours and acts as both the basal and on-demand pain control, potentially providing a more stable pain relief with fewer fluctuations. Researchers are excited about methadone because it has a longer half-life, meaning it stays active in the body longer and may require less frequent dosing adjustments, potentially leading to more consistent pain management and fewer side effects from frequent opioid use.

What evidence suggests that methadone might be an effective treatment for pain management in stem cell transplants?

Studies have shown that methadone effectively manages pain by reducing the need for other opioids in various situations, such as post-surgery and cancer-related pain. Methadone works differently in the brain compared to other pain medicines like morphine, potentially offering better pain relief. In this trial, participants in the experimental arm will receive methadone therapy every 8 hours, along with an on-demand PCA. Research indicates that methadone can be particularly helpful during bone marrow transplants, improving pain control when used with standard pain treatments. Some studies suggest that adding methadone to other pain medications can enhance overall function and reduce the amount of pain medicine needed. This evidence supports the idea that methadone could effectively reduce pain from mouth sores during stem cell transplants. ^{1 2 3 4 5}

Who Is on the Research Team?

Victor M Aquino, MD

Principal Investigator

UT Southwestern Department of Pediatric Oncology and Stem Cell Transplant

Are You a Good Fit for This Trial?

This trial is for children aged 6-18 who need a stem cell transplant due to conditions like aplastic anemia, leukemia, or severe combined immunodeficiency. They must be experiencing mucositis from chemotherapy/radiation and have not found relief with standard pain medication alone.

Inclusion Criteria

Informed consent will be obtained from all participants or their parents or guardians, assent will be obtained from children ages 10-17 years of age per institutional policy.

I am scheduled for a bone marrow transplant with intensive treatment to prepare.

I can do most activities but may need help.

Exclusion Criteria

History of allergic reactions attributed to compounds of similar chemical or biologic composition to morphine or other agents used in study.

History of opioid misuse disorder OR opioid risk assessment tool score >8.

My heart's electrical cycle is longer than normal before starting treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Participants receive chemotherapy and/or radiation conditioning prior to stem cell transplantation

1 week

Treatment

Participants receive either PCA opioid alone or PCA plus methadone for pain management during the transplantation period

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment until discharge

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Methadone

Trial Overview The study tests if adding methadone to the usual morphine-based pain management (PCA) can better reduce pain in children undergoing stem cell transplants. It aims to see if this combination decreases opioid use, improves function, reduces hospital stay, and allows earlier eating.

How Is the Trial Designed?

Group I: Group B: Study or Experimental Arm (n = 30) Experimental Treatment 1 Intervention

The second arm will be methadone therapy that is scheduled to be given every 8 hours in addition to an on demand PCA. On demand PCA dosing will be the same as control arm but with NO basal/continuous rate. Intravenous methadone will be replacing basal infusion and serve as basal drug in place of continuous medication. * Starting dose for intravenous methadone is 0.1 mg/kg IV Q8hr up to a maximum of 50 kg. Singular starting methadone will be maximum of 5 mg. * Methadone may be increased by 20-50% every 48 hours due to half-life of medication. Reduction in analgesia will need to be monitored daily following a change. However, additional methadone increase should not occur until 48 hours have passed to allow for steady state of new dose to take effect. Reduction of methadone dosing by 20-50% can be made anytime per discretion of provider or if concerned about an adverse effect from the methadone. This will continue until engraftment or until medicine is no longer needed.

Group II: Group A: Control Arm (n = 30) Active Control 1 Intervention

Pt will receive: PCA opioid will include morphine OR hydromorphone (if patient has a sensitivity or is unable to tolerate or allergic to morphine). This is the exclusive medication/opioid in this arm. The starting doses will be as follows: * Starting dose for basal infusion of morphine is 0.02 mg/kg/hour up to a maximum of 50 kg. * Starting PCA dose for morphine is 0.02 mg/kg every 15 minutes for a lockout of 0.1 mg/kg up to a maximum of 50 kg or ideal body weight (PCA starting dose should be no more than 1 mg/push and no more than 5 mg/hour lockout). * Starting dose for basal infusion of hydromorphone is 0.003 mg/kg/hour up to a maximum of 50 kg IBW. * Starting PCA dose for hydromorphone is 0.003 mg/kg every 15 minutes for an hourly maximum lockout of 0.012 mg/kg up to a maximum of 50 kg (PCA start * PCA medications may be titrated up or down by 20-50% each day for desired analgesic effect with improved pain score, continue to engraftment or when medicine is no longer needed.

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Published Research Related to This Trial

Intravenous methadone has been shown to provide effective postoperative pain relief and reduce the need for other opioids, with a similar safety profile to other opioid analgesics, based on a review of multiple studies.

While there is promising evidence for the use of intravenous methadone in managing chronic cancer pain, more research is needed to fully understand its efficacy in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous Methadone for Perioperative and Chronic Cancer Pain: A Review of the Literature. Mercadante, S.[2023]

Methadone is an effective option for managing severe cancer pain, especially neuropathic pain that doesn't respond well to other opioids or when side effects from those opioids are problematic.

There is a need for better understanding of methadone's pharmacokinetics and accurate dosage conversion, as many existing charts underestimate its potency, which can lead to a risk of toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The rediscovery of methadone for cancer pain management. Ayonrinde, OT., Bridge, DT.[2013]

Citations

1. withpower.com withpower.com/trial/phase-3-anemia-aplastic-7-2025-6ea60

Methadone for Pain Management in Stem Cell Transplants Intravenous methadone has been shown to provide effective postoperative pain relief and reduce the need for other opioids, with a similar safety profile to ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06940570

NCT06940570 | Methadone as an Alternative Treatment for ... If methadone is effective in decreasing pain, then patients may benefit in the future from using these two medications up front when getting a transplant.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4375035/

Pain Management for Children during Bone Marrow and ... We concluded that patient- and caregiver-controlled analgesia is a well-tolerated modality for pain control during hospitalization for transplantation at this ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1526590020300444

Methadone in Pain Management: A Systematic Review Analgesic effectiveness of methadone was demonstrated in different types of pain, including postprocedural, cancer-related, nociceptive, and neuropathic pain.

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/pbc.30614

The management of pain during pediatric hematopoietic ... The adjuvant use of N-methyl-D-aspartate (NMDA) antagonists like ketamine and methadone appear to be effective for children's pain during HSCT ...