Renal FailurePhase 2NCT01270932
Lenalidomide & High Dose Dexamethasone for Untreated Multiple Myeloma Renal Failure Patients
A Phase 2 study testing Lenalidomide and Dexamethasone in people with Renal Failure and Multiple Myeloma, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
Primary: To validate the initial dosing recommendations for newly diagnosed MM (Mutiple Myeloma) patients with various degrees of renal failure using pharmacokinetic studies Secondary: To evaluate the safety of lenalidomide and dexamethasone as induction therapy in newly-diagnosed MM (Multiple Myeloma) patients with… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Failure, Multiple Myeloma
- What is being tested?
- Lenalidomide and Dexamethasone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteCanada
- Study dates
- Nov 2010to 18 Dec 2017
- 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
- Subjects must meet the following inclusion/exclusion criteria to be eligible for the study.
- Patients must fulfill all of the following criteria to be eligible for admission to the study:
- Understand and voluntarily sign an informed consent form
- Age≥18 years at the time of signing the informed consent form.
- Able to adhere to the study visit schedule and other protocol requirements.
- Previously untreated, symptomatic multiple myeloma as defined by ALL 3 criteria below:
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- Monoclonal plasma cells in the bone marrow ≥10% and/or presence of a biopsy-proven plasmacytoma
- Monoclonal protein present in the serum and/or urine
- Myeloma-related organ dysfunction (at least one of the following):
- C - Calcium elevation in blood (serum calcium >upper limit of normal) R - Renal insufficiency (serum creatinine >177umol/L) A - Anemia (hemoglobin <100g/L or 20g/L below normal) B - Lytic bone lesions or osteoporosis
- Eligible for autologous stem cell transplantation as per Princess Margaret Hospital criteria.
- Disease measurable by serum or urine M (monoclonal) protein, free light chain assay, bone marrow plasmacytosis or plasmacytoma.
- No prior myeloma therapy (Exception: up to 480 mg of dexamethasone is allowed within the past 28 days, as well as palliative, localized radiation therapy, without the requirement of a washout period prior enrollment).
- ECOG (Eastern Cooperative Oncology Group) performance status of ≤ 2 at study entry.
- Laboratory test results within these ranges:
- Absolute neutrophil count ≥ 1,000/mm³
- Platelet count ≥ 50,000/mm³ (untransfused)
- Total bilirubin ≤ 22 umol/L
- Aspartate transaminase (AST) also called serum glutamic oxaloacetic transaminase (SGOT) and Alanine transaminase (ALT) also called serum glutamic pyruvic transaminase (SGPT) ≤ 2 x ULN (upper limit number) or ≤ 5 x ULN if hepatic metastases are present.
- Renal function must be measured by 24hour urine for creatinine clearance (CrCl) - any level of CrCl is allowed for eligibility.
- Disease free of prior malignancies for ≥ 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix or breast.
- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL ( milli-International Units per milliliter ) within 7 - 14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP (Females of childbearing potential) must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
- Able to take aspirin 81mg daily as prophylactic anticoagulation [patients intolerant to ASA (Acetyl Salicylic acid - Aspirin) may use low molecular weight heparin].
Who cannot join
- Patients who fulfill any of the following criteria are not eligible for admission to the study:
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
- Pregnant or breast-feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
- Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
- Use of any other experimental drug or therapy, except for up to 480 mg of dexamethasone or palliative, localized radiation therapy, without the requirement of a washout period prior enrollment.
- Known hypersensitivity to thalidomide.
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- The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
- Any prior use of lenalidomide.
- Concurrent use of other anti-cancer agents or treatments.
- Known positive for HIV (Human immunodeficiency virus) or infectious hepatitis, type B or C.
- Evidence of AL (amyloid light chain) amyloidosis
Trial locations and contacts
1 site in 1 country.
Canada1 site
University Health Network- Princess Margaret Hosptial
Toronto, Ontario, M5G2M9
About this study
Official title: An Open-label, Pharmacokinetic Study of Lenalidomide (Revlimid) and High-dose Dexamethasone Induction Therapy in Previously Untreated Multiple Myeloma Patients With Various Degrees of Renal Dysfunction - Validation of Official Dosing Guidelines for Renal Failure
Primary:
- To validate the initial dosing recommendations for newly diagnosed MM (Mutiple Myeloma) patients with various degrees of renal failure using pharmacokinetic studies
Secondary:
- To evaluate the safety of lenalidomide and dexamethasone as induction therapy in newly-diagnosed MM (Multiple Myeloma) patients with renal dysfunction using modified dosing guidelines
- To evaluate clinical response of lenalidomide and dexamethasone after 4 cycles using the modified dosing guidelines
- To evaluate the ability to collect stem cells after 4 cycles of lenalidomide and dexamethasone induction therapy in MM (Multiple Myeloma) patients with renal failure
Read the detailed description
STUDY DESIGN:
This is a single institution open label, pharmacokinetic validation study of the combination of lenalidomide with dexamethasone for firstline induction therapy in transplant-eligible MM ( Multiple Myeloma ) patients with various degrees of renal failure. There will be 4 patient groups with various degrees of renal function (based on creatinine clearance calculated from a 24 hour urine collection and requirement for dialysis). Each group will receive lenalidomide dosing as per official recommended guidelines:
Group 1 Normal {CrCl(creatinine clearance)>60 mL/min}25 mg (full-dose)-Daily for 21 days of a 28 Day cycle1 Group 2 Moderate renal impairment {30 ≤ CrCl (creatinine clearance) <60 mL/min}10 mg Daily for 21 days of a 28 day cycle Group 3 Severe renal impairment {CrCl (creatinine clearance)<30 mL/min, not requiring dialysis}15 mg Every 48 hours for 21 days of a 28 day cycle (11 PLANNED DOSES EACH 28 DAY CYCLE) Group 4 End-stage renal failure {CrCl (creatinine clearance)<30 mL/min, requiring dialysis}5 mg Once daily for 21 days of a 28 day cycle On dialysis days the dose should be administered following dialysis.
Pharmacokinetic (PK) studies: We will be evaluating PK studies following single and multiple doses of lenalidomide during Cycle 1.Patients will receive their first dose of lenalidomide (Cycle 1, day 1) as per the above designated patient group. PK (pharmacokinetic)sampling for 1st dose only will be drawn at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose for group 1 and at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 hours for all other groups. The 2nd dose of lenalidomide will be administered on Day 4 for all patients (i.e. no doses on Days 2 and 3). On Day 17 (after 14 doses of lenalidomide administered), repeat PK sampling will be performed at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours for groups 1, 2 and 4 (before next hemodialysis for those in group 4). Repeat PK sampling for group 3 will be performed at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48 hours.
- Conditions
- Renal Failure, Multiple Myeloma
- Being tested
- Lenalidomide and Dexamethasone
- Medical subject headings
- Renal Insufficiency, Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lenalidomide and DexamethasoneDrug
Also called Revlimid for Lenalidomide, Decadron for Dexamethasone
Lenalidomide:Daily for 21 days of a 28 day cycle Dexamethasone:Days 1-4, 9-12, 17-20 for the first cycle and then weekly dexamethasone from cycles 2-4.
| Study group | Role | What they receive |
|---|---|---|
| Lenalidomide and Dexamethasone | Experimental | Lenalidomide:Daily for 21 days of a 28 day cycle
Dexamethasone:Days 1-4, 9-12, 17-20 for the first cycle and then weekly dexamethasone from cycles 2-4. Receives: Drug: Lenalidomide and Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum Pharmacokinetic (PK) analysis of Study drug Lenalidomide
PK data will be analyzed and reported after completion of PK studies in all patients
Measured: 16 months
Secondary outcomes (3)
Evaluable for toxicity
All patients will be evaluable for toxicity from the time of their first treatment with Lenalidomide and dexamethasone.
Measured: 5 months
Evaluable for response
All patients who have received at least 1 cycle of therapy and have their disease re-evaluated will be considered evaluable for response.
Measured: 5 months
Overall and progression free survival rates which will be calculated by the method of Kaplan and Meier.
Measured: 16 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2011 (estimated)
- Study startNov 2010
- Primary completion18 Dec 2017
- Study completion18 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Renal FailureStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- 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
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01270932
- Sponsor's protocol ID
- RV-MM-PI-0505
- Status last verified
- Dec 2017
- First submitted
- 13 Dec 2010
- Last updated
- 29 Dec 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Chen CI, Cao Y, Trudel S, Reece DE, Kukreti V, Tiedemann R, Prica A, Paul H, Le LW, Levina O, Kakar S, Lau A, Chen H, Chen E. An open-label, pharmacokinetic study of lenalidomide and dexamethasone therapy in previously untreated multiple myeloma (MM) patients with various degrees of renal impairment - validation of official dosing guidelines. Leuk Lymphoma. 2020 Aug;61(8):1860-1868. doi: 10.1080/10428194.2020.1747064. Epub 2020 May 31.
PubMed 32476520
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Pharmacokinetic Study of Lenalidomide (Revlimid) and High-dose Dexamethasone Induction Therapy in Previously Untreated Multiple Myeloma Patients With Various Degrees of Renal Dysfunction - Validation of Official Dosing Guidelines for Renal Failure
- ClinicalTrials.gov ID
- NCT01270932
- Acronym / sponsor ID
- RV-MM-PI-0505
- Conditions
- Renal Failure, Multiple Myeloma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- Nov 2010
- Primary completion
- 18 Dec 2017 (actual)
- Study completion
- 18 Dec 2017 (actual)
- First posted
- 5 Jan 2011 (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.
Primary:
- To validate the initial dosing recommendations for newly diagnosed MM (Mutiple Myeloma) patients with various degrees of renal failure using pharmacokinetic studies
Secondary:
- To evaluate the safety of lenalidomide and dexamethasone as induction therapy in newly-diagnosed MM (Multiple Myeloma) patients with renal dysfunction using modified dosing guidelines
- To evaluate clinical response of lenalidomide and dexamethasone after 4 cycles using the modified dosing guidelines
- To evaluate the ability to collect stem cells after 4 cycles of lenalidomide and dexamethasone induction therapy in MM (Multiple Myeloma) patients with renal failure
Detailed description
STUDY DESIGN:
This is a single institution open label, pharmacokinetic validation study of the combination of lenalidomide with dexamethasone for firstline induction therapy in transplant-eligible MM ( Multiple Myeloma ) patients with various degrees of renal failure. There will be 4 patient groups with various degrees of renal function (based on creatinine clearance calculated from a 24 hour urine collection and requirement for dialysis). Each group will receive lenalidomide dosing as per official recommended guidelines:
Group 1 Normal {CrCl(creatinine clearance)>60 mL/min}25 mg (full-dose)-Daily for 21 days of a 28 Day cycle1 Group 2 Moderate renal impairment {30 ≤ CrCl (creatinine clearance) <60 mL/min}10 mg Daily for 21 days of a 28 day cycle Group 3 Severe renal impairment {CrCl (creatinine clearance)<30 mL/min, not requiring dialysis}15 mg Every 48 hours for 21 days of a 28 day cycle (11 PLANNED DOSES EACH 28 DAY CYCLE) Group 4 End-stage renal failure {CrCl (creatinine clearance)<30 mL/min, requiring dialysis}5 mg Once daily for 21 days of a 28 day cycle On dialysis days the dose should be administered following dialysis.
Pharmacokinetic (PK) studies: We will be evaluating PK studies following single and multiple doses of lenalidomide during Cycle 1.Patients will receive their first dose of lenalidomide (Cycle 1, day 1) as per the above designated patient group. PK (pharmacokinetic)sampling for 1st dose only will be drawn at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose for group 1 and at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 hours for all other groups. The 2nd dose of lenalidomide will be administered on Day 4 for all patients (i.e. no doses on Days 2 and 3). On Day 17 (after 14 doses of lenalidomide administered), repeat PK sampling will be performed at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours for groups 1, 2 and 4 (before next hemodialysis for those in group 4). Repeat PK sampling for group 3 will be performed at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48 hours.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lenalidomide and Dexamethasone | Experimental | Drug: Lenalidomide and DexamethasoneLenalidomide:Daily for 21 days of a 28 day cycle Dexamethasone:Days 1-4, 9-12, 17-20 for the first cycle and then weekly dexamethasone from cycles 2-4. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Subjects must meet the following inclusion/exclusion criteria to be eligible for the study.
- Patients must fulfill all of the following criteria to be eligible for admission to the study:
- Understand and voluntarily sign an informed consent form
- Age≥18 years at the time of signing the informed consent form.
- Able to adhere to the study visit schedule and other protocol requirements.
Key exclusion criteria (11 listed)
- Patients who fulfill any of the following criteria are not eligible for admission to the study:
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 |
|---|---|---|
| Lenalidomide and DexamethasoneAlso: Revlimid for Lenalidomide, Decadron for DexamethasoneLenalidomide:Daily for 21 days of a 28 day cycle Dexamethasone:Days 1-4, 9-12, 17-20 for the first cycle and then weekly dexamethasone from cycles 2-4. | Drug | Lenalidomide and Dexamethasone |
Primary outcome
Serum Pharmacokinetic (PK) analysis of Study drug Lenalidomide
Time frame: 16 months
PK data will be analyzed and reported after completion of PK studies in all patients
3 secondary outcomes
Evaluable for toxicity
Time frame: 5 months
Evaluable for response
Time frame: 5 months
Overall and progression free survival rates which will be calculated by the method of Kaplan and Meier.
Time frame: 16 months
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 29 Dec 2017.
- Derived from this study: PubMed 32476520Chen CI, Cao Y, Trudel S, Reece DE, Kukreti V, Tiedemann R, Prica A, Paul H, Le LW, Levina O, Kakar S, Lau A, Chen H, Chen E. An open-label, pharmacokinetic study of lenalidomide and dexamethasone therapy in previously untreated multiple myeloma (MM) patients with various degrees of renal impairment - validation of official dosing guidelines. Leuk Lymphoma. 2020 Aug;61(8):1860-1868. doi: 10.1080/10428194.2020.1747064. Epub 2020 May 31.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Lenalidomide and Dexamethasone in people with Renal Failure and Multiple Myeloma, run by University Health Network, Toronto at 1 site in Canada.
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 23 inclusion and 11 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 29 Dec 2017. 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 Canada. 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?
Serum Pharmacokinetic (PK) analysis of Study drug Lenalidomide (time frame: 16 months). 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 NCT01270932, which also lists 1 linked publication.
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 29 Dec 2017.