Clarithromycin in Multiple Myeloma Induction Therapy (CLAIM)
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| ClinicalTrials.gov Identifier: NCT02573935 |
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Recruitment Status :
Terminated
(Suspected side effects to the combination of clarithromycin and VCD (bortezomib, cyclophosphamide and dexamethasone))
First Posted : October 12, 2015
Last Update Posted : September 20, 2016
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Multiple Myeloma | Drug: Clarithromycin Drug: Placebo Drug: VCD induction therapy | Phase 2 |
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 Type : | Interventional (Clinical Trial) |
| 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 : | January 2015 |
| Actual Primary Completion Date : | September 2016 |
| Actual Study Completion Date : | September 2016 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Clarithromycin
Clarithromycin combined with VCD induction therapy
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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) |
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Placebo Comparator: Placebo
Placebo combined with VCD induction therapy
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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) |
- Comparison of number of participants with very good partial response or better response after three courses of VCD combined with clarithromycin or placebo [ Time Frame: 10 weeks ]
- 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 [ Time Frame: Five months ]
- Comparison of number of participants with sCR, CR, PR, PD or SD in the treatment groups after induction therapy and HDT, respectively [ Time Frame: Five months ]
- Comparison of frequency of infections in patients treated VCD combined with clarithromycin or placebo [ Time Frame: 9 weeks ]
- Comparison of number of stem cells harvested in patients treated with clarithromycin and placebo in combination with VCD [ Time Frame: Three months ]
- Neurotoxicity assessed by FACT/GOG-Ntx, Version 4.0 [ Time Frame: Five months ]
- Quality of life assessed by EORTC QLQ-MY20 [ Time Frame: Five months ]
- Quality of life assessed by EORTC QLQ-C30 [ Time Frame: Five months ]
- Comparison of adverse events in patients treated VCD combined with clarithromycin or placebo assessed by CTCAE v4.0 [ Time Frame: Three months ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02573935
| Denmark | |
| Department of Hematology, Aalborg University Hospital | |
| Aalborg, Denmark, 9000 | |
| Department of Hematology, Aarhus University Hospital | |
| Aarhus, Denmark, 8000 | |
| Department of Hematology, Rigshospitalet | |
| Copenhagen, Denmark, 2100 | |
| Department of Hematology, Herlev Hospital | |
| Herlev, Denmark, 2730 | |
| Department of Hematology, Odense University Hospital | |
| Odense, Denmark, 5000 | |
| Department of Hematology, Roskilde Hospital | |
| Roskilde, Denmark, 4000 | |
| Department of Hematology, Vejle Hospital | |
| Vejle, Denmark, 7100 | |
| Principal Investigator: | Henrik Gregersen, MD | Aalborg University Hospital |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Henrik Gregersen, Consultant, Aalborg University Hospital |
| ClinicalTrials.gov Identifier: | NCT02573935 |
| Other Study ID Numbers: |
DMSG 03/14 2014-002187-32 ( EudraCT Number ) |
| First Posted: | October 12, 2015 Key Record Dates |
| Last Update Posted: | September 20, 2016 |
| Last Verified: | September 2016 |
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Multiple Myeloma Clarithromycin Induction Chemotherapy Transplantation, Autologous |
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Multiple Myeloma 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 Clarithromycin Anti-Bacterial Agents Anti-Infective Agents Protein Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors |