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Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

60 Participants Needed

Methadone for Pain Management in Stem Cell Transplants
(MATCH Trial)

Overseen ByKiley 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 GroupAll 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 DataThis treatment has passed at least one previous human trial

Trial Summary

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.

What data supports the effectiveness of the drug methadone for pain management in stem cell transplants?

Methadone is known to be effective in managing severe cancer pain, especially when other opioids are not effective or cause too many side effects. It has been shown to provide effective pain relief in both acute and chronic pain situations, such as after surgery, and may help reduce the need for other opioids.¹ ² ³ ⁴ ⁵

Is methadone safe for pain management in humans?

Methadone is generally considered safe for pain management when used carefully, with attention to dosing and monitoring, especially in patients new to opioids. It is important to be aware of potential side effects like heart rhythm issues, and it should be prescribed by experienced healthcare providers.² ³ ⁶ ⁷ ⁸

How is the drug methadone unique for pain management in stem cell transplants?

Methadone is unique because it is a potent opioid that can manage severe pain, especially neuropathic pain, which other opioids may not effectively address. It has excellent oral absorption, no active metabolites, and can be used in patients who have developed tolerance to other opioids, but it requires careful dosing due to its long and unpredictable half-life.³ ⁹ ¹⁰ ¹¹ ¹²

What is the purpose of this trial?

Mucositis is a normal side effect of stem cell transplant which happens as a result of chemotherapy being given prior to a new donor cell infusion (bone marrow transplant). The chemotherapy will kill cancer cells, but good cells, such as those in the mouth, are killed too. The mouth cells going away causes the areas in the mouth to be blistered, irritated, sore, and extremely painful. Pain medication (usually morphine or hydromorphone if allergic to morphine) are given when oral blisters are seen or felt by patient in patient's mouth. However, one pain medication given through a vein in the patient may or may not be effective and providers are often challenged with providing good pain control while waiting for the new donor cells to grow, which will then heal the mouth. This is a period of waiting that is 6-8 weeks.The investigators know that methadone, a second pain medication, may decrease pain in a different way than morphine. This is because methadone works in a different way in the brain than morphine. By giving these pain medicines together, the hope of the study is to show decreased pain while waiting for new cells to grow.The goal of this clinical trial is to hope to learn whether adding methadone (second pain medication) to the current pain medication which is morphine alone (all patients will receive this pain medication) will help reduce the pain experience of participant. Current treatment of morphine alone is sometimes not entirely effective and so any improvement of pain while waiting for new cells to grow is one of the goals of this study. 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.Participant in this study between 6-18 years of age and is needing a stem cell transplant for a disease that can potentially be cured by transplantation.Participant in this study is receiving chemotherapy and/or radiation conditioning that can cause mucositis. Participants are being asked to participate in this study because participants meet criteria to receive methadone that may or may not reduce pain experience versus just being given morphine alone, which is what all patients are given when the participants have mucositis.The main goal of the study is to see if less opioid (pain medication) when methadone is added in comparison to participant who uses PCA only. The investigators also want to learn if patient's overall function is improved if given methadone. Another goal would be to see the number of TPN days the participant received and if the participant who was given methadone began to eat sooner. Other smaller goals include learning about side effects of methadone, and if the hospital stay is less for those who receive the study medication.This medication will be given at Children's Medical Center of Dallas while participant is admitted for the stem cell transplant. There is no sponsor that is funding the study and this drug will be given free of charge in exchange for participation in the study

Research Team

Victor M Aquino, MD

Principal Investigator

UT Southwestern Department of Pediatric Oncology and Stem Cell Transplant

Eligibility Criteria

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.

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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.

See 5 more

Timeline

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

Treatment Details

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.

Participant Groups

2Treatment groups

Experimental Treatment

Active Control

Group I: Group B: Study or Experimental Arm (n = 30)Experimental Treatment1 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 Control1 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.

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Findings from Research

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]