A Study to Desensitize Allergic Reactions to Treatments for Blood Disorders

Study Overview
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Brief Summary
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Patients with multiple myeloma (a type of blood cancer affecting the white blood cells) or amyloidosis (abnormal buildup of a protein called amyloid in the body) are often given treatment with the drugs lenalidomide or pomalidomide. Some patients may experience an allergic reaction to these drugs which would mean stopping the treatment. The purpose of this research study is to see how safe and useful desensitization is in allowing patients to receive further treatment with lenalidomide or pomalidomide.

Detailed Description
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Some doctors believe that the body may be taught to react less or stop reacting to, the things that would otherwise trigger an allergic reaction. This is called desensitization. Desensitization is usually done with repeat exposure to the thing that causes the allergic reaction. For example, people who have allergies may receive small, controlled doses of the allergen over a period of time until the allergic reactions are tolerable or are stopped completely. The researchers want to see if giving low doses of lenalidomide or pomalidomide to people who experienced an allergic reaction to these medications can become desensitized so that they are able to continue treatment for their disease with these drugs.

Official Title
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Desensitization of Immunomodulating Agent-Related Hypersensitivity Reactions as a Means to Provide Therapeutic Options in the Management of Plasma Cell Disorders (DeHyperPCD)

Conditions
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Multiple Myeloma, Amyloidosis

Intervention / Treatment
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* Drug: Lenalidomide
* Drug: Pomalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed Informed Consent Adult patients 18 years old or older All study participants must be registered into the mandatory Lenalidomide or Pomalidomide Pregnancy Prevention Plan, and be willing and able to comply with the requirements. Females of reproductive potential must adhere to the pregnancy testing and contraceptive techniques as required by the Pregnancy Prevention Plan. Patient diagnosed with multiple myeloma or amyloidosis, with history of HSR to lenalidomide or pomalidomide, who had experienced moderate-severe (Grade ≥2 CTCAE v5.0) cutaneous reactions to IMiDs, with or without being symptomatic (itchy rash). Patients who developed HSR to IMiDs (lenalidomide or pomalidomide) will be assessed according to the CTCAE v 5.0 grading criteria during enrolment, and the severity of the grading (Grade ≥ 2 or otherwise) is recorded for the purpose of future subgroup analysis. OR Complained of angioedema or anaphylaxis reactions attributable to lenalidomide or pomalidomide. Patients must be afebrile at least 48 hours prior to proposed desensitization day. For patients with existing body rash, a complete resolution of rash is needed prior to Rapid Desensitization Program procedures at least 7 days prior to desensitization. Patients may continue to administer their current medication prior to the start of Rapid Desensitization Program (RDP). Best possible medication history will be taken prior to RDP, with the exception of withholding beta- blockers on the day of desensitization. Patient's allergy history will be documented. Exclusion Criteria: Female who is pregnant or suspected of being pregnant or breast feeding or likely to breast feed during the study duration Inability to take oral medications. History of Steven-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Patients who are taking IMiDs-based therapy for an indication other than multiple myeloma (MM) and/or systemic amyloidosis (AL). The development of erythema nodosum, if characterized by a desquamating rash while taking thalidomide, IMiDs or similar drugs. Active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine or previous infection (HepB core Ab +, but HepB sAg negative) are eligible. Patients who, for whatever reason, are unable to tolerate IMiDs (other than hypersensitivity reactions). Patients who have completed 3 RDPs and continued to have breakthrough hypersensitivity reactions (HSR) post Rapid Desensitization Program (RDP). Patients who had experienced IMiDs-related hypersensitivity reaction that is less than Grade 2 (Grade 1) as per CTCAE v5.0.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lenalidomide<br>Participants will only receive lenalidomide if they had previously received this drug as a part of their treatment for multiple myeloma or amyloidosis and had experienced an allergic reaction to the drug. Participants will first be given a low dose of lenalidomide with increasing doses over 10-12 steps over 3.5 to 5 hours. Participants will be monitored for side effects or reactions prior to each dose step and any reactions will be managed before giving the increased dose at the next step. The final dose will be determined by the study doctor and is expected to be the dose that participants will restart treatment with lenalidomide at. | Drug: Lenalidomide<br>* Lenalidomide is an antineoplastic and immunomodulatory agent that will be given as a liquid in syringes to be taken orally (by mouth).<br>* Other names: REVLIMID;|
| Experimental: Pomalidomide<br>Participants will only receive pomalidomide if they had previously received this drug as a part of their treatment for multiple myeloma or amyloidosis and had experienced an allergic reaction to the drug. Participants will first be given a low dose of pomalidomide with increasing doses over 10-12 steps over 3.5 to 5 hours. Participants will be monitored for side effects or reactions prior to each dose step and any reactions will be managed before giving the increased dose at the next step. The final dose will be determined by the study doctor and is expected to be the dose that participants will restart treatment with pomalidomide at. | Drug: Pomalidomide<br>* Pomalidomide is an antineoplastic and immunomodulatory agent that will be given as a liquid in syringes to be taken orally (by mouth).<br>* Other names: POMALYST;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants successfully completing desensitization program |  | 12 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distress Assessment and Response Tool (DART) score | Rating of physical symptoms, practical concerns, and emotional concerns on a scale from 1-10. 0 = no symptoms/concerns, 10=worse possible experience of the symptom/concern | 90 days post desensitization program | 
| Edmonton Symptom Assessment System (ESAS) score | A rating of nine common symptoms on a scale from 0-10. 0 = no symptoms, 10=worse possible experience of the symptom | 90 days post desensitization program | 
| Frequency of interrupted treatment with immunomodulating agent |  | 90 days post desensitization program | 
| Duration of interrupted treatment with immunomodulating agent |  | 90 days post desensitization program | 
| Mortality rate associated with disease progression or treatment-related toxicity |  | 90 days post desensitization program | 
| Frequency of rash recurrence |  | 90 days post desensitization | 
| Duration of treatment with immunomodulating agent post desensitization |  | 90 days post desensitization | 
| Incidence of adverse events during desensitization procedures and hospital stay |  | 12 days | 
| Total duration of treatment with immunomodulating agent |  | 90 days post desensitization | 
| Duration of treatment with supportive care agents |  | 90 days post desensitization |