Multiple MyelomaPhase 2CLAIMNCT02573935
Clarithromycin in Multiple Myeloma Induction Therapy
A Phase 2 study testing Clarithromycin and VCD induction therapy in people with Multiple Myeloma, run by Henrik Gregersen at 7 sites in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Clarithromycin and VCD induction therapy
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 58 participants
- Where
- 7 sitesDenmark
- Study dates
- Jan 2015to Sep 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Denmark7 sites
Department of Hematology, Aalborg University Hospital
Aalborg, 9000
Department of Hematology, Aarhus University Hospital
Aarhus, 8000
Department of Hematology, Rigshospitalet
Copenhagen, 2100
Department of Hematology, Herlev Hospital
Herlev, 2730
Department of Hematology, Odense University Hospital
Odense, 5000
Department of Hematology, Roskilde Hospital
Roskilde, 4000
Department of Hematology, Vejle Hospital
Vejle, 7100
About this study
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
This study evaluates the potential synergic anti-myeloma activity of clarithromycin when combined with VCD induction therapy in patients with newly diagnosed multiple myeloma.
Read the 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.
- Conditions
- Multiple Myeloma
- Being tested
- Clarithromycin, Placebo, VCD induction therapy
- Keywords
- Multiple Myeloma, Clarithromycin, Induction Chemotherapy, Transplantation, Autologous
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClarithromycinDrug
p.o. clarithromycin 500 mg twice daily for 63 days
PlaceboDrug
Placebo tablet twice daily for 63 days
VCD induction therapyDrug
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)
| Study group | Role | What they receive |
|---|---|---|
| Clarithromycin | Experimental | Clarithromycin combined with VCD induction therapy Receives: Drug: Clarithromycin; Drug: VCD induction therapy |
| Placebo | Placebo comparator | Placebo combined with VCD induction therapy Receives: Drug: Placebo; Drug: VCD induction therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of number of participants with very good partial response or better response after three courses of VCD combined with clarithromycin or placebo
Measured: 10 weeks
Secondary outcomes (8)
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
Measured: Five months
Comparison of number of participants with sCR, CR, PR, PD or SD in the treatment groups after induction therapy and HDT, respectively
Measured: Five months
Comparison of frequency of infections in patients treated VCD combined with clarithromycin or placebo
Measured: 9 weeks
Comparison of number of stem cells harvested in patients treated with clarithromycin and placebo in combination with VCD
Measured: Three months
Neurotoxicity assessed by FACT/GOG-Ntx, Version 4.0
Measured: Five months
Quality of life assessed by EORTC QLQ-MY20
Measured: Five months
Quality of life assessed by EORTC QLQ-C30
Measured: Five months
Comparison of adverse events in patients treated VCD combined with clarithromycin or placebo assessed by CTCAE v4.0
Measured: Three months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2015 (estimated)
- Study startJan 2015
- Primary completionSep 2016
- Study completionSep 2016
Why it stopped: Suspected side effects to the combination of clarithromycin and VCD (bortezomib, cyclophosphamide and dexamethasone)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Henrik Gregersen
- Sponsor type
- University, hospital or other
- Collaborators
- Danish Myeloma Study Group
- Responsible party
- Sponsor-investigator, Henrik Gregersen, Aalborg University Hospital
- Investigators
- Henrik Gregersen, MD, Principal investigator, Aalborg University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02573935
- Sponsor's protocol ID
- DMSG 03/14
- Other IDs
- 2014-002187-32, 2014
- Acronym
- CLAIM
- Status last verified
- Sep 2016
- First submitted
- 8 Oct 2015
- Last updated
- 20 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 20645430Nielsen LK, Klausen TW, Jarden M, Frederiksen H, Vangsted AJ, Do T, Kristensen IB, Frolund UC, Andersen CL, Abildgaard N, Gregersen H. Clarithromycin added to bortezomib-cyclophosphamide-dexamethasone impairs health-related quality of life in multiple myeloma patients. Eur J Haematol. 2019 Jan;102(1):70-78. doi: 10.1111/ejh.13175. Epub 2018 Oct 29.
PubMed 30230047Gregersen H, Do T, Kristensen IB, Frolund UC, Andersen NF, Nielsen LK, Andersen CL, Klausen TW, Vangsted AJ, Abildgaard N. 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. Exp Hematol Oncol. 2018 Aug 13;7:18. doi: 10.1186/s40164-018-0110-0. eCollection 2018.
PubMed 30123673
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02573935
- Acronym / sponsor ID
- CLAIM / DMSG 03/14
- Conditions
- Multiple Myeloma
- Keywords
- Multiple Myeloma, Clarithromycin, Induction Chemotherapy, Transplantation, Autologous
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Suspected side effects to the combination of clarithromycin and VCD (bortezomib, cyclophosphamide and dexamethasone)
- Enrolment
- 58 participants (actual)
- Lead sponsor
- Henrik GregersenUniversity, hospital or other
- Collaborators
- Danish Myeloma Study Group
- Study start
- Jan 2015
- Primary completion
- Sep 2016 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 12 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the potential synergic anti-myeloma activity of clarithromycin when combined with VCD induction therapy in patients with newly diagnosed multiple myeloma.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Clarithromycin | Experimental | Drug: Clarithromycin, Drug: VCD induction therapyClarithromycin combined with VCD induction therapy |
| Placebo | Placebo comparator | Drug: Placebo, Drug: VCD induction therapyPlacebo combined with VCD induction therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Clarithromycinp.o. clarithromycin 500 mg twice daily for 63 days | Drug | Clarithromycin |
| PlaceboPlacebo tablet twice daily for 63 days | Drug | Placebo |
| VCD induction therapyThree 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) | Drug | Clarithromycin, Placebo |
Primary outcome
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
8 secondary outcomes
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
Results and safety
The study was stopped early (reason given: Suspected side effects to the combination of clarithromycin and VCD (bortezomib, cyclophosphamide and dexamethasone)). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2016.
- Background: PubMed 20645430Gay 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.
- Derived from this study: PubMed 30230047Nielsen LK, Klausen TW, Jarden M, Frederiksen H, Vangsted AJ, Do T, Kristensen IB, Frolund UC, Andersen CL, Abildgaard N, Gregersen H. Clarithromycin added to bortezomib-cyclophosphamide-dexamethasone impairs health-related quality of life in multiple myeloma patients. Eur J Haematol. 2019 Jan;102(1):70-78. doi: 10.1111/ejh.13175. Epub 2018 Oct 29.
- Derived from this study: PubMed 30123673Gregersen H, Do T, Kristensen IB, Frolund UC, Andersen NF, Nielsen LK, Andersen CL, Klausen TW, Vangsted AJ, Abildgaard N. 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. Exp Hematol Oncol. 2018 Aug 13;7:18. doi: 10.1186/s40164-018-0110-0. eCollection 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Henrik Gregersen, MD principal investigator
Aalborg University Hospital
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Clarithromycin and VCD induction therapy in people with Multiple Myeloma, run by Henrik Gregersen at 7 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Suspected side effects to the combination of clarithromycin and VCD (bortezomib, cyclophosphamide and dexamethasone)). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02573935, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2016.