Loratadine for Stem Cell Transplant Bone Pain

Overseen By Rammy Khadour

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AHS Cancer Control Alberta

Must not be taking: Antihistamines, Analgesics

Disqualifiers: Hypersensitivity to antihistamines, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 days

78 Participants Needed

Trial Summary

What is the purpose of this trial?

The research question for the current study is: Is loratadine more effective than placebo in preventing G-CSF-related bone pain during autologous hematopoetic stem cell transplant in patients with lymphoma or multiple myeloma? The hypothesis is that prophylaxis with loratadine will help prevent or reduce the severity of bone pain in this setting.

Will I have to stop taking my current medications?

The trial requires that you stop using antihistamines two days before the study starts, except for single doses during chemotherapy or blood transfusions. You also need to stop regular use of pain relievers four days before starting G-CSF.

What data supports the effectiveness of the drug loratadine for treating bone pain in stem cell transplant patients?

Loratadine has been shown to be effective in reducing symptoms of allergic conditions like hay fever and chronic urticaria, and it is well tolerated with minimal side effects. While there is no direct evidence for its use in treating bone pain from stem cell transplants, its effectiveness in other conditions suggests it may have potential benefits. ^{1 2 3 4 5}

Is loratadine safe for humans?

Loratadine is generally safe for humans, with common mild side effects like headache, fatigue, and dry mouth. It is well tolerated and has a low incidence of adverse effects, similar to a placebo in studies. ^{3 4 6 7 8}

How is the drug Loratadine unique for treating bone pain after stem cell transplant?

Loratadine, commonly used for allergies, is being explored for bone pain after stem cell transplants, which is unique because there are no standard treatments specifically for this type of pain. Unlike typical pain medications, Loratadine is an antihistamine that may help by reducing inflammation, offering a novel approach to managing this condition. ^{9 10 11 12 13}

Eligibility Criteria

This trial is for adults over 18 with lymphoma or multiple myeloma who are about to have a stem cell transplant. They should be relatively healthy, able to follow the study plan, and not have used antihistamines or painkillers recently. People with severe diseases like heart failure or diabetes that aren't well-managed can't join.

Inclusion Criteria

My cancer is either lymphoma or multiple myeloma, confirmed by lab tests.

I am able to care for myself and perform daily activities.

I do not have any severe illnesses like heart failure, uncontrolled diabetes, liver or kidney failure.

Exclusion Criteria

I haven't taken antihistamines in the last two days, except a single dose during chemotherapy or a blood transfusion.

I have started or continued taking pain medication regularly in the last four days.

I have not used G-CSF or pegfilgrastim in the last 12 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive loratadine or placebo starting 3 hours before the first dose of G-CSF and continue daily for a minimum of 8 days

8-12 days

Daily monitoring (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• Loratadine
• Placebo

Trial Overview The trial is testing if Loratadine, an antihistamine, can prevent or lessen bone pain caused by G-CSF injections in patients undergoing stem cell transplants compared to a placebo (a substance with no active drug).

Participant Groups

Group I: Loratadine Arm Experimental Treatment 1 Intervention

Loratadine 10mg, administered initially 3 hours before the first dose of G-CSF in the autologous stem cell mobilization protocol, and then daily for a minimum of 8 days.

Group II: Placebo Arm Placebo Group 1 Intervention

Placebo capsule, administered initially 3 hours before the first dose of G-CSF in the autologous stem cell mobilization protocol, and then daily for a minimum of 8 days.

Loratadine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Loratadine for:

• Allergic rhinitis
• Urticaria

Approved in European Union as Loratadine for:

• Allergic rhinitis
• Urticaria

Approved in Canada as Loratadine for:

• Allergic rhinitis
• Urticaria

Who Is Running the Clinical Trial?

AHS Cancer Control Alberta

Lead Sponsor

Trials

188

Recruited

26,900+

Findings from Research

In an eight-week clinical trial with 25 patients, loratadine significantly improved lung function parameters by up to 21% and reduced apneic events by about 52%, indicating its efficacy as an adjunct treatment for persistent allergic bronchial asthma.

71% of patients reported a good therapeutic response to loratadine, and there was a notable decrease in the use of inhalative sympathomimetics, suggesting that loratadine effectively alleviates asthma symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Allergic bronchial asthma treated with Loratadine]. Kroll, VM., Nothofer, B., Werdermann, K.[2013]

In a 28-day study involving patients with chronic idiopathic urticaria, loratadine (10 mg once daily) was found to be significantly more effective than placebo in reducing symptoms, with 64% of patients reporting marked or complete relief.

Loratadine was well tolerated, showing no sedative or anticholinergic side effects, making it a safer option compared to terfenadine, which had some reported side effects like sedation and dry mouth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effects of loratadine and terfenadine in the treatment of chronic idiopathic urticaria. Belaich, S., Bruttmann, G., DeGreef, H., et al.[2013]

Loratadine is an effective long-acting antihistamine that has been shown to be superior to placebo and as effective as other antihistamines for treating allergic rhinitis and chronic urticaria, based on large clinical studies.

It is well tolerated with fewer sedative effects compared to other antihistamines, making it a suitable first-line treatment option, especially since serious side effects like ventricular arrhythmias have not been reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loratadine. A reappraisal of its pharmacological properties and therapeutic use in allergic disorders. Haria, M., Fitton, A., Peters, DH.[2018]

In a study involving 107 hay fever patients, loratadine (40 mg once daily) was found to significantly reduce allergy symptoms compared to placebo, outperforming clemastine (1 mg twice daily) in effectiveness.

Loratadine did not cause sedation, while clemastine had a higher sedation rate, making loratadine a safer option for treating hay fever without the drowsiness associated with some antihistamines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of hay fever with loratadine--a new non-sedating antihistamine. Irander, K., Odkvist, LM., Ohlander, B.[2019]

In a study of 139 allergic patients with acute rhinosinusitis, the addition of loratadine to standard treatment (antibiotics and corticosteroids) significantly improved symptoms like sneezing and nasal obstruction compared to placebo.

Patients receiving loratadine showed greater overall improvement as rated by physicians, indicating that loratadine can enhance symptom control in acute sinusitis management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunct effect of loratadine in the treatment of acute sinusitis in patients with allergic rhinitis. Braun, JJ., Alabert, JP., Michel, FB., et al.[2019]

In a 15-day study involving 30 patients with grass pollen allergies, the combination of 5 mg loratadine and 120 mg pseudoephedrine significantly reduced total allergy symptoms, including nasal stuffiness, sneezing, and eye irritation.

The treatment was well tolerated with no serious side effects reported, and only mild side effects like sedation and dry mouth occurred in 3 to 7 percent of patients, indicating it is both safe and effective for managing seasonal allergic rhinitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evaluation of the efficiency and safety of the loratadine with pseudoephedrine combination drug in treatment of seasonal allergic rhinitis]. Zawisza, E., Lipiec, A., Rapiejko, P.[2013]

The fixed-dose combination of loratadine and montelukast (L/M) was well tolerated in over 3800 subjects across 19 clinical studies, showing a low incidence of adverse events (AEs) comparable to placebo and individual monotherapies.

The most common adverse event reported was headache (4.5%), but most AEs were mild and short-lived, with no significant changes in laboratory tests or vital signs, indicating that L/M is a safe option for treating allergic rhinitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of fixed-dose loratadine/montelukast in subjects with allergic rhinitis. Prenner, BM., Lu, S., Danzig, MR.[2021]

Loratadine is a nonsedating antihistamine that effectively relieves symptoms of allergic rhinitis and urticaria, with a quick onset of action within 1 hour and a duration of at least 24 hours, making it suitable for once-daily dosing.

It has a low incidence of sedation and adverse reactions, comparable to placebo, and shows minimal potential for drug interactions, making it a safe option for treating acute allergic reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loratadine: a nonsedating antihistamine with once-daily dosing. Barenholtz, HA., McLeod, DC.[2019]

A 6.1-year-old child developed calcineurin-induced pain syndrome (CIPS) after receiving cyclosporine during his second hematopoietic stem cell transplant, with severe leg pain occurring during the drug infusion.

Switching from cyclosporine to tacrolimus and starting amlodipine for hypertension effectively resolved the pain, suggesting that alternative calcineurin inhibitors and calcium-channel blockers may help manage CIPS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyclosporine-induced pain syndrome in a child undergoing hematopoietic stem cell transplant. Lavoratore, SR., Navarro, OM., Grunebaum, E., et al.[2013]

A 42-year-old woman with relapsed Philadelphia-positive acute lymphoblastic leukemia successfully achieved molecular remission after treatment with chemotherapy and imatinib mesylate, followed by a second allogeneic bone marrow transplantation.

She experienced a rare complication known as calcineurin-inhibitor induced pain syndrome (CIPS) after the transplant, which was resolved by stopping the medication and using analgesics, highlighting the need for awareness of this potential side effect in similar patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Acute lymphoblastic leukemia presenting with calcineurin-inhibitor induced pain syndrome after a second allogeneic bone marrow transplantation]. Takashima, S., Numata, A., Miyamoto, T., et al.[2014]

A 10-year-old boy developed Complex Regional Pain Syndrome (CIPS) after a second allogeneic bone marrow transplant (BMT) for severe aplastic anemia, highlighting a rare complication in pediatric patients post-transplant.

Despite experiencing severe pain and bone marrow edema, the patient's condition improved naturally after 43 days without stopping the tacrolimus treatment, which was within the therapeutic range at the onset of symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calcineurin-inhibitor-induced pain syndrome after a second allogeneic bone marrow transplantation for a child with aplastic anemia. Nishikawa, T., Okamoto, Y., Tanabe, T., et al.[2014]

Calcineurin-inhibitor induced pain syndrome (CIPS) is a newly recognized complication in patients receiving immunosuppressive medications, particularly tacrolimus, after transplantation.

This study is significant as it reports the first case of tacrolimus-associated CIPS in pediatric patients, highlighting the need for awareness and management of this pain syndrome in young transplant recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tacrolimus-induced pain syndrome in a pediatric orthotopic liver transplant patient. Malat, GE., Dupuis, RE., Kassman, B., et al.[2019]

Severe pain is a common experience for patients undergoing haematopoietic stem cell transplantation (HSCT) at all stages, from stem cell mobilization to long-term recovery.

The primary source of pain during HSCT is damage to mucosal tissues caused by the conditioning regimen, but other pain sources have also been identified, highlighting the need for comprehensive pain management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pain syndromes in the setting of haematopoietic stem cell transplantation for haematological malignancies. Niscola, P., Romani, C., Scaramucci, L., et al.[2011]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[Allergic bronchial asthma treated with Loratadine]. [2013]

2. United States pubmed.ncbi.nlm.nih.gov

Comparative effects of loratadine and terfenadine in the treatment of chronic idiopathic urticaria. [2013]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Loratadine. A reappraisal of its pharmacological properties and therapeutic use in allergic disorders. [2018]

4. Denmark pubmed.ncbi.nlm.nih.gov

Treatment of hay fever with loratadine--a new non-sedating antihistamine. [2019]

5. Denmark pubmed.ncbi.nlm.nih.gov

Adjunct effect of loratadine in the treatment of acute sinusitis in patients with allergic rhinitis. [2019]

6. Poland pubmed.ncbi.nlm.nih.gov

[Evaluation of the efficiency and safety of the loratadine with pseudoephedrine combination drug in treatment of seasonal allergic rhinitis]. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Safety of fixed-dose loratadine/montelukast in subjects with allergic rhinitis. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Loratadine: a nonsedating antihistamine with once-daily dosing. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Cyclosporine-induced pain syndrome in a child undergoing hematopoietic stem cell transplant. [2013]

10. Japan pubmed.ncbi.nlm.nih.gov

[Acute lymphoblastic leukemia presenting with calcineurin-inhibitor induced pain syndrome after a second allogeneic bone marrow transplantation]. [2014]

11. Denmark pubmed.ncbi.nlm.nih.gov

Calcineurin-inhibitor-induced pain syndrome after a second allogeneic bone marrow transplantation for a child with aplastic anemia. [2014]

12. Denmark pubmed.ncbi.nlm.nih.gov

Tacrolimus-induced pain syndrome in a pediatric orthotopic liver transplant patient. [2019]

13. England pubmed.ncbi.nlm.nih.gov

Pain syndromes in the setting of haematopoietic stem cell transplantation for haematological malignancies. [2011]