Efficacy Study of Revlimid® and Low Dose Continuously Administered Melphalan to Treat Higher Risk Myelodysplastic Syndromes (REMMYDYS)
This study has been completed.
Information provided by (Responsible Party):
Dr. Rena Buckstein, Sunnybrook Health Sciences Centre
First received: August 29, 2008
Last updated: December 11, 2012
Last verified: December 2012
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.
Leukemia, Myelomonocytic, Chronic
Drug: Lenalidomide and melphalan
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||Revlimid®, and Metronomic Melphalan in the Management of Higher Risk Myelodysplastic Syndromes (MDS) and CMML: a Phase 2 Study"
Primary Outcome Measures:
- Overall Response Rate (RR) (as defined by modified international working group standardized response criteria) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Percent with hematologic improvement [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Percent with cytogenetic remission [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Overall, progression-free and leukemia-free-survival [ Time Frame: 3 yrs ] [ Designated as safety issue: No ]
- Percent reduction in baseline biomarkers of angiogenesis including: circulating endothelial cells (CEC) and precursors (CEP), plasma and marrow VEGF and VEGFR 1-2 levels [ Time Frame: 3 yrs ] [ Designated as safety issue: No ]
- Safety (type, frequency, severity, and relationship of adverse events to study therapy) [ Time Frame: 3 yrs ] [ Designated as safety issue: Yes ]
| Estimated Enrollment:
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||January 2012 (Final data collection date for primary outcome measure)
Drug: Lenalidomide and melphalan
Lenalidomide 10 mg po daily for 21d/28 Melphalan 2 mg po daily for 21d/28
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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).
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
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00744536
|Odette Cancer Center
|Toronto, Ontario, Canada, M4N3M5 |
Sunnybrook Health Sciences Centre
||Rena J Buckstein, MD FRCPC
||Odette Cancer Center
No publications provided
||Dr. Rena Buckstein, Head Hematology Site Group, Sunnybrook Health Sciences Centre
History of Changes
|Other Study ID Numbers:
|Study First Received:
||August 29, 2008
||December 11, 2012
||Canada: Canadian Institutes of Health Research
United States: Food and Drug Administration
Keywords provided by Sunnybrook Health Sciences Centre:
Chronic myelomonocytic leukemia
High intermediate risk and high risk IPSS score
Myelodysplastic Myeloproliferative Diseases
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on December 05, 2013
Leukemia, Myelomonocytic, Chronic
Neoplasms by Histologic Type
Bone Marrow Diseases
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Molecular Mechanisms of Pharmacological Action