A Study to Desensitize Allergic Reactions to Treatments for Blood Disorders

• ClinicalTrials.gov Identifier: NCT03959358
• Recruitment Status: Recruiting
• First Posted: May 22, 2019
• Last Update Posted: December 9, 2021
• Sponsor: University Health Network, Toronto
• Information provided by (Responsible Party): University Health Network, Toronto

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma; Amyloidosis	Drug: Lenalidomide; Drug: Pomalidomide	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 13 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Desensitization of Immunomodulating Agent-Related Hypersensitivity Reactions as a Means to Provide Therapeutic Options in the Management of Plasma Cell Disorders (DeHyperPCD)
• Actual Study Start Date: July 3, 2020
• Estimated Primary Completion Date: May 7, 2022
• Estimated Study Completion Date: October 7, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Lenalidomide; 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; Lenalidomide is an antineoplastic and immunomodulatory agent that will be given as a liquid in syringes to be taken orally (by mouth).; Other Name: REVLIMID
Experimental: Pomalidomide; 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; Pomalidomide is an antineoplastic and immunomodulatory agent that will be given as a liquid in syringes to be taken orally (by mouth).; Other Name: POMALYST

Outcome Measures

Primary Outcome Measures :

1. Number of participants successfully completing desensitization program [ Time Frame: 12 days ]

Secondary Outcome Measures :

1. Distress Assessment and Response Tool (DART) score [ Time Frame: 90 days post desensitization program ]
   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
2. Edmonton Symptom Assessment System (ESAS) score [ Time Frame: 90 days post desensitization program ]
   A rating of nine common symptoms on a scale from 0-10. 0 = no symptoms, 10=worse possible experience of the symptom
3. Frequency of interrupted treatment with immunomodulating agent [ Time Frame: 90 days post desensitization program ]
4. Duration of interrupted treatment with immunomodulating agent [ Time Frame: 90 days post desensitization program ]
5. Mortality rate associated with disease progression or treatment-related toxicity [ Time Frame: 90 days post desensitization program ]
6. Frequency of rash recurrence [ Time Frame: 90 days post desensitization ]
7. Duration of treatment with immunomodulating agent post desensitization [ Time Frame: 90 days post desensitization ]
8. Incidence of adverse events during desensitization procedures and hospital stay [ Time Frame: 12 days ]
9. Total duration of treatment with immunomodulating agent [ Time Frame: 90 days post desensitization ]
10. Duration of treatment with supportive care agents [ Time Frame: 90 days post desensitization ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Anca Prica, M.D.; 416-946-2249; anca.prica@uhn.ca

Locations

Canada, Ontario

Princess Margaret Cancer Centre; Recruiting

Toronto, Ontario, Canada, M5G 2M9

Contact: Anca Prica, M.D. 416-946-2249 anca.prica@uhn.ca

Principal Investigator: Anca Prica, M.D.

Sponsors and Collaborators

University Health Network, Toronto

Investigators

• Principal Investigator: Anca Prica, M.D.; Princess Margaret Cancer Centre

More Information

• Responsible Party: University Health Network, Toronto
• ClinicalTrials.gov Identifier: NCT03959358
• Other Study ID Numbers: DeHyperPCD; RV-CL-MM-PI-13170 ( Other Identifier: Princess Margaret Cancer Centre )
• First Posted: May 22, 2019
• Last Update Posted: December 9, 2021
• Last Verified: November 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Multiple Myeloma; Amyloidosis; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Proteostasis Deficiencies; Metabolic Diseases; Lenalidomide; Pomalidomide; Immunologic Factors; Physiological Effects of Drugs; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antineoplastic Agents