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

NCT00744536 | Completed Phase 2 DMC

• 1 other identifier: RV-MDS-PI-128
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic; Angiogenesis

Keywords

Myelodysplastic syndrome; Chronic myelomonocytic leukemia; High intermediate risk and high risk IPSS score; Angiogenesis; Metronomic chemotherapy; Myelodysplastic Myeloproliferative Diseases

Outcome Measures

Primary Outcomes (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).

  3 years

Secondary Outcomes (5)

• Percent with hematologic improvement

  3 years

• Percent with cytogenetic remission

  3 years

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

  3 yrs

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

  3 yrs

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

  3 yrs

Study Arms (1)

Lenalidomide and Melphalan

EXPERIMENTAL

Lenalidomide + Melphalan both given metronomically

Drug: Lenalidomide and melphalan

Interventions

Lenalidomide and melphalan DRUG

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

Also known as: Revlimid, Melphalan

Lenalidomide and Melphalan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead
• Celgene: collaborator

Study Sites (1)

Sunnybrook Health Sciences Centre, Odette Cancer Center

Toronto, Ontario, M4N3M5, Canada

Location

Related Publications (1)

• 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.

  PMID: 24819395 DERIVED

Related Links

• Published online to Leukemia Research

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic; Myelodysplastic-Myeloproliferative Diseases

Interventions

Lenalidomide; Melphalan

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Rena J Buckstein, MD FRCPC

  Odette Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head Hematology Site Group

Study Record Dates

• First Submitted: August 29, 2008
• First Posted: September 1, 2008
• Study Start: January 1, 2008
• Primary Completion: January 1, 2012
• Study Completion: December 1, 2012
• Last Updated: June 9, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)