AzTrials
AzTrials

Myelodysplastic SyndromesPhase 2REMMYDYSNCT00744536

Efficacy Study of Revlimid® and Low Dose Continuously Administered Melphalan to Treat High Risk MDS

A Phase 2 study testing Lenalidomide and melphalan in people with Myelodysplastic Syndromes and Leukemia, Myelomonocytic, Chronic, run by Sunnybrook Health Sciences Centre at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Angiogenesis increases in higher risk MDS patients and those with proliferative CMML. Angiogenesis is associated with increased risk of leukemic transformation and poorer prognoses. Low dose chemotherapy may have anti-angiogenic properties by targetting the genetically stable endothelial cells. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Lenalidomide and melphalan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteCanada
Study dates
Jan 2008to Dec 2012
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

  • Understand and voluntarily sign an informed consent form.
  • Age 18 years or older at the time of signing the informed consent form.
  • Able to adhere to the study visit schedule and other protocol requirements.
  • Must have a diagnosis of high-intermediate or high risk MDS (de novo or secondary) or CMML fitting any of the following classifications (including CMML with wbc < 12,000 x 109/L) and IPSS > 1.5 or proliferative form of CMML (wbc > 12,000 x 109/L for which the IPSS does not apply). If the patient has unsuccessful cytogenetics, patients with WHO classification of transfusion dependent RAEB-1 will be eligible (see appendix B and C for WHO MDS classification).
  • All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 4 weeks (6 weeks for 5-Azacitidine or bone marrow transplant) prior to treatment in this study.
  • ECOG performance status of <= 2 at study entry (see Appendix A).
Show all 11Show fewer
  • Laboratory test results within these ranges:
  • Serum calcium <3.0 mmol/L
  • Serum creatinine < 1.5 mg/dL
  • Total bilirubin < 1.5 mg/dL
  • AST (SGOT) and ALT (SGPT) < 2 x ULN

Who cannot join

  • 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 within 28 days of baseline.
  • Known hypersensitivity to thalidomide or melphalan.
  • The development of erythema nodosum is characterized by a desquamating rash while taking thalidomide or similar drugs.
Show all 16Show fewer
  • Any prior use of lenalidomide.
  • Concurrent use of other anti-cancer agents or treatments.
  • Known positive for HIV or infectious hepatitis, types A, B or C.
  • Must not have a diagnosis of AML (> 20% blasts) or other progressive malignant disease
  • Must not have received treatment with, erythropoietin, or granulocyte colony-stimulating factors within seven days of study initiation (21 days for pegfilgrastim or Aranesp). Note: use of corticosteroids (topical and inhaled) is permitted and prophylactic steroids are allowed for transfusion reactions, but ongoing oral corticosteroids are not permitted.
  • Serious or non-healing wound, ulcer, or bone fracture.
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment.
  • Any history of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to study entry.
  • Histories of myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within 12 months prior to study entry.
  • History of pulmonary embolism within the past 12 months.

Trial locations and contacts

1 site in 1 country.

Canada1 site
  • Sunnybrook Health Sciences Centre, Odette Cancer Center

    Toronto, Ontario, M4N3M5

Other trials in Canada

About this study

Official title: Revlimid®, and Metronomic Melphalan in the Management of Higher Risk Myelodysplastic Syndromes (MDS) and CMML: A Phase 2 Study"

Angiogenesis increases in higher risk MDS patients and those with proliferative CMML. Angiogenesis is associated with increased risk of leukemic transformation and poorer prognoses. Low dose chemotherapy may have anti-angiogenic properties by targetting the genetically stable endothelial cells. Lenalidomide has been recently shown to be highly effective as monotherapy in low/low-intermediate risk MDS, particularly in the subgroup harboring a 5q- deletion. Lenalidomide has not been well studied in higher risk MDS although there are some reports of lenalidomide's efficacy in RAEB-T and AML. One potential mode of action of lenalidomide is inhibition of angiogenesis. The investigators hypothesize that by combining lenalidomide with low dose melphalan in higher risk MDS the investigators will more effectively block angiogenesis and achieve responses or hematologic improvement in MDS.

Read the detailed description

STUDY OBJECTIVES:

Primary:

  1. Determine the overall response rates of low dose melphalan used in combination with lenalidomide in higher risk MDS

Secondary:

  1. Determine the frequency of hematologic improvement of low dose melphalan used in combination with lenalidomide in higher risk MDS·
  2. Determine the safety and tolerability of low dose melphalan used in combination with lenalidomide in higher risk MDS·
  3. Determine the effects of low dose melphalan used in combination with lenalidomide on biomarkers of angiogenesis in higher risk MDS·
  4. Determine the frequency of cytogenetic remissions of low dose melphalan used in combination with lenalidomide in higher risk MDS

STUDY DESIGN:

This study is a single center, open-label, non-randomized Phase II study. Patients with higher risk MDS are included. This patient population will be defined by either high intermediate or high risk IPSS scores or proliferative CMML with symptomatic cytopenias or hypersplenism (IPSS score does not apply). If cytogenetics are unavailable, patients with transfusion dependent RAEB-1 will be eligible.

This is an open label, single center non-randomized Phase II study of melphalan 2 mg po and lenalidomide, 10 mg po daily on days 1 - 21 of a 28 day cycle in adult patients with higher risk MDS. Patients may continue to receive drug for a maximum of 12 months or until one of the following occur: death; disease progression (for definition, see appendix D); intercurrent illness that prevents further administration of treatment; unacceptable adverse event(s); patient decides to withdraw from the study; or if general or specific changes in the patient's condition make the patient unsuitable for further treatment, or if after 4 cycles the patient is not deriving clinical benefit from the treatment in the judgment of the investigator. After 12 months, responding patients may continue on oral lenalidomide alone daily (at the dose tolerated by the patient) for 21 days of a 28 day cycle until disease progression, toxicity or death.

Response to treatment and disease progression will be assessed by collecting and evaluating bone marrow aspirates within 10 days of the first dose of cycles 3 and 5 and every three cycles thereafter (every 12 weeks) until confirmation of a complete response. Once confirmed 1 month later, patients will not undergo bone marrow assessments until there is evidence of progression.

Blood tests will include weekly CBC with differential and platelet count, electrolytes, BUN and creatinine for the first 8 weeks, then every 2 weeks until on stable doses, then every 4 weeks thereafter or as clinically indicated. Liver profile will be measured monthly. Bone marrow biopsies/aspirates will be centrally reviewed during or at the end of the study. Approximately 30 days after receiving the last dose of study drug, patients will be reassessed for toxicity, patient status and relapse/progression if applicable. Thereafter, patients will be re-assessed every 3 months until death or loss to follow-up.

Biomarkers of angiogenesis will be measured at the following frequencies: CECs and CEPs at baseline, monthly x 3 then q 3 monthly x 2 then at time of progression or coming off study.Marrow and peripheral blood soluble VEGF and VEGFR-1 and 2 will be measured by ELISA at the same frequency as the bone marrows.Cytogenetics will be performed at baseline, at 3 months and at completion of the study.

STUDY DURATION: 12 months for lenalidomide + melphalan; option to remain on lenalidomide alone if ongoing response at 12 months TOTAL SAMPLE SIZE: 20

Being tested
Lenalidomide and melphalan
Keywords
Myelodysplastic syndrome, Chronic myelomonocytic leukemia, High intermediate risk and high risk IPSS score, Angiogenesis, Metronomic chemotherapy, Myelodysplastic Myeloproliferative Diseases
Medical subject headings
Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic, Myelodysplastic-Myeloproliferative Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Lenalidomide and melphalanDrug

    Also called Revlimid, Melphalan

    Lenalidomide (Revlimid) 10 mg po daily for 21d/28 Melphalan (Melphalan) 2 mg po daily for 21d/28

Study groups in NCT00744536
Study groupRoleWhat they receive
Lenalidomide and MelphalanExperimentalLenalidomide + Melphalan both given metronomically
Receives: Drug: Lenalidomide and melphalan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rate (RR) (as defined by modified international working group standardized response criteria)

    Overall Response Rate (RR) (as defined by modified international working group standardized response criteria).

    Measured: 3 years

Secondary outcomes (5)
  1. Percent with hematologic improvement

    Percent with hematologic improvement.

    Measured: 3 years

  2. Percent with cytogenetic remission

    Percent with cytogenetic remission.

    Measured: 3 years

  3. Overall, progression-free and leukemia-free-survival

    Overall, progression-free and leukemia-free-survival.

    Measured: 3 yrs

  4. Percent reduction in baseline biomarkers of angiogenesis including: circulating endothelial cells (CEC) and precursors (CEP), plasma and marrow VEGF and VEGFR 1-2 levels

    Percent reduction in baseline biomarkers of angiogenesis including: circulating endothelial cells (CEC) and precursors (CEP), plasma and marrow VEGF and VEGFR 1-2 levels.

    Measured: 3 yrs

  5. Safety (type, frequency, severity, and relationship of adverse events to study therapy)

    Safety (type, frequency, severity, and relationship of adverse events to study therapy).

    Measured: 3 yrs

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Sep 2008 (estimated)
  2. Study startJan 2008
  3. Primary completionJan 2012
  4. Study completionDec 2012

Resources

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
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00744536
Sponsor's protocol ID
RV-MDS-PI-128
Acronym
REMMYDYS
Status last verified
Jun 2017
First submitted
29 Aug 2008
Last updated
9 Jun 2017
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Buckstein R, Kerbel R, Cheung M, Shaked Y, Chodirker L, Lee CR, Lenis M, Davidson C, Cussen MA, Reis M, Chesney A, Zhang L, Mamedov A, Wells RA. Lenalidomide and metronomic melphalan for CMML and higher risk MDS: a phase 2 clinical study with biomarkers of angiogenesis. Leuk Res. 2014 Jul;38(7):756-63. doi: 10.1016/j.leukres.2014.03.022. Epub 2014 Apr 5.

    PubMed 24819395

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lenalidomide and melphalan in people with Myelodysplastic Syndromes and Leukemia, Myelomonocytic, Chronic, run by Sunnybrook Health Sciences Centre 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 11 inclusion and 16 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 9 Jun 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?

Overall Response Rate (RR) (as defined by modified international working group standardized response criteria) (time frame: 3 years). 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 NCT00744536, 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 9 Jun 2017.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in