CLAIM: Clarithromycin in Multiple Myeloma Induction Therapy

• Sponsor: Henrik Gregersen (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02573935
• Collaborator: Danish Myeloma Study Group (Other)
• Enrollment: 58
• Locations: 7
• Arms: 2
• Duration (Months): 20
• Patients Per Site: 8.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study evaluates the potential synergic anti-myeloma activity of clarithromycin when combined with VCD induction therapy in patients with newly diagnosed multiple myeloma.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Clarithromycin; Drug: Placebo; Drug: VCD induction therapy	Phase 2

Detailed Description

The survival in younger myeloma patients improved in the nineties with the introduction of high-dose melphalan with autologous stem cell support (HDT). However, all patients will eventually experience relapse after HDT and there is a need for improvement of the response after HDT. The choice of induction treatment before HDT affects the outcome after induction therapy as well as the outcome after HDT.

Clarithromycin is a macrolide antibiotic frequently utilized in the treatment of respiratory tract infections and is often used in patients with known hypersensitivity to beta-lactam antibiotic. Besides antibiotic activity, clarithromycin may exert immunomodulatory and anti-inflammatory effects. The toxicity profile of clarithromycin is favourable and the cost is very low.

Studies on cell lines have shown that clarithromycin attenuates autophagy in myeloma cells and a recent study has demonstrated that treatment with clarithromycin enhanced bortezomib-induced cytotoxicity in myeloma cells. Phase II studies without control groups have indicated that clarithromycin might enhance the effect of the thalidomide and lenalidomide. A case-matched analysis compared patients at one centre receiving clarithromycin, lenalidomide and dexamethasone with an equal number of patients at another centre receiving lenalidomide and dexamethasone. This study indicated a favourable effect of clarithromycin with a higher frequency of complete response, very-good-partial-response or better response and progression-free survival. However, there is a need for controlled studies to determine whether clarithromycin might enhance the effect of other myeloma agents.

This randomized placebo-controlled study will include 160 patients with newly diagnosed multiple myeloma eligible for HDT. The study evaluates the potential synergic anti-myeloma activity of clarithromycin when combined with VCD induction therapy in patients with newly diagnosed multiple myeloma, and is conducted by the Danish Myeloma Study Group (DMSG) at seven clinics in Denmark. The first patient was included in May 2015 and enrolment is expected to continue until October 2016. The study ends when the last included patient has been followed for two months after HDT.

Study Design

• Study Type: Interventional
• Actual Enrollment: 58 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized Placebo-controlled Phase II Study of Clarithromycin or Placebo Combined With VCD Induction Therapy Prior to High-dose Melphalan With Stem Cell Support in Patients With Newly Diagnosed Multiple Myeloma
• Study Start Date: Jan 1, 2015
• Actual Primary Completion Date: Sep 1, 2016
• Actual Study Completion Date: Sep 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Clarithromycin Clarithromycin combined with VCD induction therapy	Drug: Clarithromycin; p.o. clarithromycin 500 mg twice daily for 63 days; Drug: VCD induction therapy; Three courses of VCD (sc bortezomib 1.3 mg/sqm days 1, 4, 8, 11, iv cyclophosphamide 500 mg/sqm on days 1 and 8, and p.o. dexamethasone 40 mg days 1, 2, 4, 5, 8, 9, 11, 12 in each 21-days course)
Placebo Comparator: Placebo Placebo combined with VCD induction therapy	Drug: Placebo; Placebo tablet twice daily for 63 days; Drug: VCD induction therapy; Three courses of VCD (sc bortezomib 1.3 mg/sqm days 1, 4, 8, 11, iv cyclophosphamide 500 mg/sqm on days 1 and 8, and p.o. dexamethasone 40 mg days 1, 2, 4, 5, 8, 9, 11, 12 in each 21-days course)

Outcome Measures

Primary Outcome Measures

1. Comparison of number of participants with very good partial response or better response after three courses of VCD combined with clarithromycin or placebo [10 weeks]

Secondary Outcome Measures

1. Comparison of number of participants with very good partial response or better response after HDT in patients treated with three courses of VCD combined with clarithromycin or placebo [Five months]

2. Comparison of number of participants with sCR, CR, PR, PD or SD in the treatment groups after induction therapy and HDT, respectively [Five months]

3. Comparison of frequency of infections in patients treated VCD combined with clarithromycin or placebo [9 weeks]

4. Comparison of number of stem cells harvested in patients treated with clarithromycin and placebo in combination with VCD [Three months]

5. Neurotoxicity assessed by FACT/GOG-Ntx, Version 4.0 [Five months]

6. Quality of life assessed by EORTC QLQ-MY20 [Five months]

7. Quality of life assessed by EORTC QLQ-C30 [Five months]

8. Comparison of adverse events in patients treated VCD combined with clarithromycin or placebo assessed by CTCAE v4.0 [Three months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Myeloma diagnosis according to IMWG criteria

• Treatment demanding disease

• High-dose melphalan with stem cell support scheduled as a part of the treatment

• Signed informed consent given prior to any study related activities

• Age > 18 years

Exclusion Criteria:

• Allogeneic transplantation scheduled as a part of the treatment

• Myeloma treatment prior to entry in the study, except radiotherapy, bisphosphonates/denosumab or corticosteroids for symptom control

• Concurrent disease making clarithromycin treatment unsuitable

• Positive pregnancy test (only applicable for women with childbearing potential)

• Known or suspected hypersensitivity or intolerance to clarithromycin

• Prolonged QT corrected (QTc) interval ( > 500 msec on screening ECG)

• Concurrent treatment with cabergoline, fluconazole, ketoconazole, pimozide, quetiapine, sirolimus, verapamil, tacrolimus, ergot alkaloid, simvastatin or other statins

• Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrolment, uncontrolled angina or known cardiac amyloidosis

• Severe renal dysfunction (estimated creatinine clearance <10 mL/min)

• Serious medical or psychiatric illness which, in the judgment of the investigator, would make the patient inappropriate for entry into the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Hematology, Aalborg University Hospital	Aalborg		Denmark	9000
2	Department of Hematology, Aarhus University Hospital	Aarhus		Denmark	8000
3	Department of Hematology, Rigshospitalet	Copenhagen		Denmark	2100
4	Department of Hematology, Herlev Hospital	Herlev		Denmark	2730
5	Department of Hematology, Odense University Hospital	Odense		Denmark	5000
6	Department of Hematology, Roskilde Hospital	Roskilde		Denmark	4000
7	Department of Hematology, Vejle Hospital	Vejle		Denmark	7100

Sponsors and Collaborators

• Henrik Gregersen
• Danish Myeloma Study Group

Investigators

• Principal Investigator: Henrik Gregersen, MD, Aalborg University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

• Gay F, Rajkumar SV, Coleman M, Kumar S, Mark T, Dispenzieri A, Pearse R, Gertz MA, Leonard J, Lacy MQ, Chen-Kiang S, Roy V, Jayabalan DS, Lust JA, Witzig TE, Fonseca R, Kyle RA, Greipp PR, Stewart AK, Niesvizky R. Clarithromycin (Biaxin)-lenalidomide-low-dose dexamethasone (BiRd) versus lenalidomide-low-dose dexamethasone (Rd) for newly diagnosed myeloma. Am J Hematol. 2010 Sep;85(9):664-9. doi: 10.1002/ajh.21777.

• Responsible Party: Henrik Gregersen, Consultant, Aalborg University Hospital
• ClinicalTrials.gov Identifier: NCT02573935
• Other Study ID Numbers: DMSG 03/14; 2014-002187-32
• First Posted: Oct 12, 2015
• Last Update Posted: Sep 20, 2016
• Last Verified: Sep 1, 2016

• Keywords provided by Henrik Gregersen, Consultant, Aalborg University Hospital: Multiple Myeloma; Clarithromycin; Induction Chemotherapy; Transplantation, Autologous
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Clarithromycin

Study Results

No Results Posted as of Sep 20, 2016