Multiple MyelomaPhase 2NCT02206503
Cyclophosphamide With Biochemical Progression During Lenalidomide-Dexamethasone Treatment for Relapsed/Refractory Multiple Myeloma (MM)
A Phase 2 study testing Cyclophosphamide, Lenalidomide and Dexamethasone in people with Multiple Myeloma, run by Fondazione EMN Italy Onlus at 1 site in Italy.
Trial summary
This study evaluates the efficacy of the addiction of Cyclophosphamide to Revlimid-low dose dexamethasone (Rd) in relapsed/refractory Multiple Myeloma patients, who experienced a biochemical progression, without CRAB, during Rd treatment. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Cyclophosphamide, Lenalidomide and Dexamethasone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteItaly
- Study dates
- Mar 2013to Jul 2018
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patient with relapse/refractory multiple myeloma who experienced biochemical progression, without CRAB, during treatment with Rd. CRAB means the presence of organ damage, multiple myeloma related (renal impairment and/or anemia and/or new bone lesions and/or hypercalcemia). It is sufficient one of the previous signs for defining the presence of CRAB. Biochemical progression means: positivization of serum/urine immunofixation for patients who reached a complete remission with Rd treatment or at least 25% increment of monoclonal component in serum/urine for patients who reached at least a stable disease (SD).
- Patient exposed to previous therapy included Lenalidomide, Thalidomide, Bortezomib and/or autologous stem cell transplantation (ASCT) and in treatment with Rd.
- Patient is, in the investigator(s) opinion, willing and able to comply with the protocol requirements.
- Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
- Female patient is either post-menopausal or surgically sterilized or, if at childbearing potential, must: understand that the study medication could have an expected teratogenic risk.
- Agree to use, and be able to comply with, effective contraception without interruption, 4 weeks before starting study drug, throughout study drug therapy (including dose interruptions) and for 4 weeks after the end of study drug therapy, even if she has amenorrhea. This applies unless the subject commits to absolute and continued abstinence confirmed on a monthly basis. The following are effective methods of contraception*:
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- Implant**
- Levonorgestrel-releasing intrauterine system (IUS)**
- Medroxyprogesterone acetate depot
- Tubal sterilisation
- Sexual intercourse with a vasectomised male partner only; vasectomy must be confirmed by two negative semen analyses
- Ovulation inhibitory progesterone-only pills (i.e., desogestrel)
- Combined oral contraceptive pills are not recommended. If a subject was using combined oral contraception, she must switch to one of the methods above. The increased risk of venous thromboembolism (VTE) continues for 4 to 6 weeks after stopping combined oral contraception.
- **prophylactic antibiotics should be considered at the time of insertion particularly in patients with neutropenia due to risk of infection.
- Agree to have a medically supervised pregnancy test with a minimum sensitivity of 25 mills International Units on milliliter (mIU/ml) not more than 3 days before the start of study medication once the subject has been on effective contraception for at least 4 weeks. This requirement also applies to women of childbearing potential who practice complete and continued abstinence.
- Agree to have a medically supervised pregnancy test every 4 weeks including 4 weeks after the end of study treatment, except in the case of confirmed tubal sterilization. These tests should be performed not more than 3 days before the start of next treatment. This requirement also applies to women of childbearing potential who practice complete and continued abstinence.
- † A female subject or a female partner of a male subject is considered to have childbearing potential unless she meets at least one of the following criteria: Age
- ≥50 years and naturally amenorrhoeic for ≥ 1 year (amenorrhoea following cancer therapy does not rule out childbearing potential), premature ovarian failure confirmed by a specialist gynaecologist, previous bilateral salpingooophorectomy or hysterectomy, xy genotype, Turner's syndrome or uterine agenesis.
- Male subjects must:
- Agree to use condoms throughout study drug therapy, during any dose interruption and for one week after cessation of study therapy if their partner is of childbearing potential and has no contraception.
- Agree not to donate semen during study drug therapy and for one week after end of study drug therapy.
- All subjects must:
- Agree to abstain from donating blood while taking study drug therapy and for one week following discontinuation of study drug therapy.
- Agree not to share study medication with another person and to return all unused study drug to the investigator.
- Patient who obtain at least a SD with Rd treatment and experienced a biochemical progression without CRAB, during the treatment itself.
- Patient has a Karnofsky performance status ≥ 60%.
- Patient has a life-expectancy > 6 months.
- Patients must have a adequate cardiac function.
- Patients must have adequate pulmonary function.
- Patient has the following laboratory values within 14 days before Baseline (day 1 of the Cyclophosphamide):
- Platelet count ≥ 50 x 109/L or ≥ 25 109/L if bone marrow involvement is ≥ 50% of plasma cells in bone marrow biopsy.
- Absolute neutrophil count (ANC) ≥ 1.0 x 109/L or ≥ 0,5 109/L x if bone marrow involvement is ≥ 50% of plasma cells in bone marrow biopsy.
- Corrected serum calcium ≤ 14 mg/dL (3.5 mmol/L).
- Aspartate transaminase (AST): ≤ 2.5 x the upper limit of normal (ULN).
- Alanine transaminase (ALT): ≤ 2.5 x the ULN.
- Total bilirubin: ≤ 1.5 x the ULN.
- Calculated or measured creatinine clearance: ≥ 30 mL/minute.
Who cannot join
- Patients with newly diagnosed multiple myeloma.
- Patients who relapsed from multiple myeloma with signs of organ damage related to disease (CRAB).
- Any serious medical condition, including the presence of laboratory abnormalities, which places the subject at an unacceptable risk if he or she participates in this study or confounds the experimental ability to interpret data from the study.
- Pregnant or lactating females.
- Prior history of malignancies, other than multiple myeloma, unless the subject has been free of the disease for ≥ 3 years. Exceptions include the following: Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, incidental histological finding of prostate cancer (TNM stage of T1a or T1b).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A PHASE II, MULTI-CENTER, OPEN LABEL STUDY OF CYCLOPHOSPHAMIDE IN MULTIPLE MYELOMA PATIENTS WITH BIOCHEMICAL PROGRESSION DURING LENALIDOMIDE-DEXAMETHASONE TREATMENT FOR RELAPSED/REFRACTORY MULTIPLE MYELOMA
This study evaluates the efficacy of the addiction of Cyclophosphamide to Revlimid-low dose dexamethasone (Rd) in relapsed/refractory Multiple Myeloma patients, who experienced a biochemical progression, without CRAB, during Rd treatment.
Read the detailed description
This protocol is a phase II multicenter, open label study designed to determine whether the addiction of Cyclophosphamide to Rd (CRd) treatment significantly increases response rates and prolonged the outcome (PFS, OS) in patients who experienced a biochemical relapse, without CRAB under Rd treatment. Patients will be evaluated at scheduled visits in up to 3 study periods: pre-treatment, treatment and long-term follow-up (LTFU).
The pre-treatment period includes: screening visits, performed at study entry. After providing written informed consent to participate in the study, patients will be evaluated for study eligibility. The screening period includes the availability of inclusion criteria described above. Subjects who meet all the inclusion criteria will be enrolled.
The treatment period includes: administration of the combination CRd for 9 cycles. In order to assess the efficacy and safety of treatment, patients will attend the study center visits at least every 2 weeks. The response will be assessed after each cycle.
During the LTFU period, after development of confirmed progression disease (PD), all patients are to be followed for survival every 1-3 months via telephone or office visit.
- Conditions
- Multiple Myeloma
- Being tested
- Cyclophosphamide, Lenalidomide, Dexamethasone
- Keywords
- LENALIDOMIDE, BIOCHEMICAL PROGRESSION, RELAPSED/REFRACTORY MM, WITHOUT CRAB
- Medical subject headings
- Multiple Myeloma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
This protocol is a phase II multicenter, open label study designed to determine whether the addition of Cyclophosphamide to Rd (CRd) treatment significantly increases response rates and prolonged the outcome (PFS, OS) in patients who experienced a biochemical relapse, without CRAB under Rd treatment. The treatment period includes: administration of the combination CRd for 9 cycles. In order to assess the efficacy and safety of treatment, patients will attend the study center visits at least every 2 weeks. The response will be assessed after each cycle. During the LTFU period, after development of confirmed PD, all patients are to be followed for survival every 1-3 months via telephone or office visit.
LenalidomideDrug
DexamethasoneDrug
| Study group | Role | What they receive |
|---|---|---|
| Cyclophosphamide; Lenalidomide; Dexamethasone | Experimental | MM Patients who experienced biochemical progression during Rd treatment without CRAB (signs of organ damage, multiple myeloma-related, as renal impairment and/or anemia and/or new bone lesions and/or hypercalcemia), will continue:
* Lenalidomide orally at the dose of 25 mg/day for 21 days every 28 days.
* Dexamethasone orally at the dose of 40 mg once a week.
Adding:
· Cyclophosphamide orally at the dose of 50 mg/day on days 1-21 every 28 days. CRd combination will be continued for 9-4week cycles. Patients will not receive any maintenance therapy. Receives: Drug: Cyclophosphamide; Drug: Lenalidomide; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy in terms of response and survival
To assess the efficacy (response rate according to International Myeloma Working Group (IMWG) definition, appendix 2) after the addiction of Cyclophosphamide to Revlimid-Dexamethasone (CRd) in Multiple Myeloma patients, who experienced a biochemical progression during Rd treatment, without myeloma-related organ damage, CRAB.
Measured: 2 years
Secondary outcomes (6)
Safety in terms of hematological and non-hematological adverse events
The following evaluations will be conducted to assess the safety:
- Adverse events
- Concomitant medication and supportive therapies
- Electrocardiogram and Chest Radiograph.
- Medical history, physical examination, neurotoxicity assessment
- Vital signs, body weight, height, and body surface area
- Clinical laboratory evaluations (hematology, chemistry)
- Health outcomes assessment
Measured: 2 years
The progression free survival (PFS)
Measured: 2 years
The overall survival (OS)
Measured: 2 years
Duration of time to progression (TTP)
Measured: 2 years
Time to next therapy (TNT)
Measured: 2 years
Identification of patient's subgroups according to specific prognostic factors
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2014 (estimated)
- Study startMar 2013
- Primary completionApr 2015
- Study completionJul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondazione EMN Italy Onlus
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Maria Teresa Petrucci, MD, Principal investigator, Policlinico Umberto I
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02206503
- Sponsor's protocol ID
- CRd
- Status last verified
- Aug 2018
- First submitted
- 6 Feb 2014
- Last updated
- 2 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A PHASE II, MULTI-CENTER, OPEN LABEL STUDY OF CYCLOPHOSPHAMIDE IN MULTIPLE MYELOMA PATIENTS WITH BIOCHEMICAL PROGRESSION DURING LENALIDOMIDE-DEXAMETHASONE TREATMENT FOR RELAPSED/REFRACTORY MULTIPLE MYELOMA
- ClinicalTrials.gov ID
- NCT02206503
- Acronym / sponsor ID
- CRd
- Conditions
- Multiple Myeloma
- Keywords
- LENALIDOMIDE, BIOCHEMICAL PROGRESSION, RELAPSED/REFRACTORY MM, WITHOUT CRAB
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Fondazione EMN Italy OnlusUniversity, hospital or other
- Study start
- Mar 2013 (actual)
- Primary completion
- Apr 2015 (actual)
- Study completion
- Jul 2018 (actual)
- First posted
- 1 Aug 2014 (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 efficacy of the addiction of Cyclophosphamide to Revlimid-low dose dexamethasone (Rd) in relapsed/refractory Multiple Myeloma patients, who experienced a biochemical progression, without CRAB, during Rd treatment.
Detailed description
This protocol is a phase II multicenter, open label study designed to determine whether the addiction of Cyclophosphamide to Rd (CRd) treatment significantly increases response rates and prolonged the outcome (PFS, OS) in patients who experienced a biochemical relapse, without CRAB under Rd treatment. Patients will be evaluated at scheduled visits in up to 3 study periods: pre-treatment, treatment and long-term follow-up (LTFU).
The pre-treatment period includes: screening visits, performed at study entry. After providing written informed consent to participate in the study, patients will be evaluated for study eligibility. The screening period includes the availability of inclusion criteria described above. Subjects who meet all the inclusion criteria will be enrolled.
The treatment period includes: administration of the combination CRd for 9 cycles. In order to assess the efficacy and safety of treatment, patients will attend the study center visits at least every 2 weeks. The response will be assessed after each cycle.
During the LTFU period, after development of confirmed progression disease (PD), all patients are to be followed for survival every 1-3 months via telephone or office visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cyclophosphamide; Lenalidomide; Dexamethasone | Experimental | Drug: Cyclophosphamide, Drug: Lenalidomide, Drug: DexamethasoneMM Patients who experienced biochemical progression during Rd treatment without CRAB (signs of organ damage, multiple myeloma-related, as renal impairment and/or anemia and/or new bone lesions and/or hypercalcemia), will continue: * Lenalidomide orally at the dose of 25 mg/day for 21 days every 28 days. * Dexamethasone orally at the dose of 40 mg once a week. Adding: · Cyclophosphamide orally at the dose of 50 mg/day on days 1-21 every 28 days. CRd combination will be continued for 9-4week cycles. Patients will not receive any maintenance therapy. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (37 listed)
- Patient with relapse/refractory multiple myeloma who experienced biochemical progression, without CRAB, during treatment with Rd. CRAB means the presence of organ damage, multiple myeloma related (renal impairment and/or anemia and/or new bone lesions and/or hypercalcemia). It is sufficient one of the previous signs for defining the presence of CRAB. Biochemical progression means: positivization of serum/urine immunofixation for patients who reached a complete remission with Rd treatment or at least 25% increment of monoclonal component in serum/urine for patients who reached at least a stable disease (SD).
- Patient exposed to previous therapy included Lenalidomide, Thalidomide, Bortezomib and/or autologous stem cell transplantation (ASCT) and in treatment with Rd.
- Patient is, in the investigator(s) opinion, willing and able to comply with the protocol requirements.
- Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
- Female patient is either post-menopausal or surgically sterilized or, if at childbearing potential, must: understand that the study medication could have an expected teratogenic risk.
Key exclusion criteria (5 listed)
- Patients with newly diagnosed multiple myeloma.
- Patients who relapsed from multiple myeloma with signs of organ damage related to disease (CRAB).
- Any serious medical condition, including the presence of laboratory abnormalities, which places the subject at an unacceptable risk if he or she participates in this study or confounds the experimental ability to interpret data from the study.
- Pregnant or lactating females.
- Prior history of malignancies, other than multiple myeloma, unless the subject has been free of the disease for ≥ 3 years. Exceptions include the following: Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, incidental histological finding of prostate cancer (TNM stage of T1a or T1b).
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 |
|---|---|---|
| CyclophosphamideThis protocol is a phase II multicenter, open label study designed to determine whether the addition of Cyclophosphamide to Rd (CRd) treatment significantly increases response rates and prolonged the outcome (PFS, OS) in patients who experienced a biochemical relapse, without CRAB under Rd treatment. The treatment period includes: administration of the combination CRd for 9 cycles. In order to assess the efficacy and safety of treatment, patients will attend the study center visits at least every 2 weeks. The response will be assessed after each cycle. During the LTFU period, after development of confirmed PD, all patients are to be followed for survival every 1-3 months via telephone or office visit. | Drug | Cyclophosphamide; Lenalidomide; Dexamethasone |
| Lenalidomide | Drug | Cyclophosphamide; Lenalidomide; Dexamethasone |
| Dexamethasone | Drug | Cyclophosphamide; Lenalidomide; Dexamethasone |
Primary outcome
Efficacy in terms of response and survival
Time frame: 2 years
To assess the efficacy (response rate according to International Myeloma Working Group (IMWG) definition, appendix 2) after the addiction of Cyclophosphamide to Revlimid-Dexamethasone (CRd) in Multiple Myeloma patients, who experienced a biochemical progression during Rd treatment, without myeloma-related organ damage, CRAB.
6 secondary outcomes
Safety in terms of hematological and non-hematological adverse events
Time frame: 2 years
The progression free survival (PFS)
Time frame: 2 years
The overall survival (OS)
Time frame: 2 years
Duration of time to progression (TTP)
Time frame: 2 years
Time to next therapy (TNT)
Time frame: 2 years
Identification of patient's subgroups according to specific prognostic factors
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 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.
Maria Teresa Petrucci, MD principal investigator
Policlinico Umberto I
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cyclophosphamide, Lenalidomide and Dexamethasone in people with Multiple Myeloma, run by Fondazione EMN Italy Onlus at 1 site in Italy.
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 37 inclusion and 5 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: finished, as of the sponsor's last update on 2 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. 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. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Efficacy in terms of response and survival (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Aug 2018.