A Trial of Lenalidomide & Azacitidine in Low Risk Myelodysplastic Syndromes

NCT ID: NCT01379274

Last Updated: 2020-11-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2013-11-30

Brief Summary

This phase II study will evaluate the safety and efficacy of combining two active agents;Revlimid® (lenalidomide) and low dose Vidaza® (azacitidine) for the treatment of patients with low to intermediate-1 MDS excluding patients with 5 q deletion. The rationale for adding Vidaza® (azacitidine) after 3 months of revlimid monotherapy is that combination therapy will result in higher response rates, and potentially longer response duration than that achieved with either agent.

STUDY OBJECTIVES:

Primary:

To determine the safety and tolerability of the combination of Revlimid® (lenalidomide) and low dose Vidaza® (azacitidine) in patients with low - intermediate-1 risk MDS non 5 q deletion who have not responded after 3 months of Revlimid® (lenalidomide) monotherapy

Secondary:

To determine the response rate in patients with low - intermediate-1 risk MDS non 5 q deletion receiving Revlimid® (lenalidomide) in combination with low dose Vidaza® (azacitidine), as defined by the IWG 2006 Revised Response Criteria

Detailed Description

Eligibility criteria

1. Understand and voluntarily sign an informed consent form.

2. Age 18 years at the time of signing the informed consent form.

3. Able to adhere to the study visit schedule and other protocol requirements.

4. Diagnosis of low- or intermediate-1-risk IPSS (see Appendix III) MDS without an abnormality of chromosome 5 involving a deletion between bands q31 and q33.

Pathologic diagnosis via pathology performed at Rush University Medical Center or made available to Rush from outside institution.

5. Prior treatment with < 3 cycles (84 days) of Revlimid® (lenalidomide) are eligible for enrollment regardless of response.

6. ECOG performance status of 2 at study entry (see Appendix II).

7. 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.

8. Serum bilirubin levels < 1.5 times the upper limit of the normal range for the laboratory (ULN). Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis.

9. Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) levels < 2 x ULN.

10. Serum creatinine levels < 1.5 x ULN

11. Absolute neutrophil count > 1000/mm³

12. Platelet count > 30,000/mm³

13. All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.

Conditions

MDS

Keywords

MDS; Low risk disease; IPSS

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

lenalidomide and azacitidine combination

Lenalidomide and azacitidine combination to be utilized in patients who did not respond to 3 months of lenalidomide monotherapy.

Group Type: EXPERIMENTAL

Lenalidomide and azacitidine combination

Intervention Type: DRUG

lenalidomide 10 mg will be administered orally on Days 1-28 of each 28-day cycle. Patients who fail to achieve an erythroid response per 2006 IWG criteria after 3 cycles of monotherapy will receive lenalidomide at the same dose administered in cycle 3 and low-dose azacitidine25 mg/m2 subcutaneously (SC) or intravenously (IV) for 5 days (on Days 1-5) of every 28-day cycle.

Patients who fail to respond (2006 IWG criteria) after receiving two cycles of combination therapy will receive lenalidomide at the same dose administered in Cycle 3 and azacitidine 50 mg/m2 SC or IV given daily on Days 1-5 of each 28-day cycle, if no grade 4 toxicity developed or no delay greater than 2 weeks in starting a new cycle was experienced during the first 2 cycles of combination therapy.

Interventions

Lenalidomide and azacitidine combination

lenalidomide 10 mg will be administered orally on Days 1-28 of each 28-day cycle. Patients who fail to achieve an erythroid response per 2006 IWG criteria after 3 cycles of monotherapy will receive lenalidomide at the same dose administered in cycle 3 and low-dose azacitidine25 mg/m2 subcutaneously (SC) or intravenously (IV) for 5 days (on Days 1-5) of every 28-day cycle.

Patients who fail to respond (2006 IWG criteria) after receiving two cycles of combination therapy will receive lenalidomide at the same dose administered in Cycle 3 and azacitidine 50 mg/m2 SC or IV given daily on Days 1-5 of each 28-day cycle, if no grade 4 toxicity developed or no delay greater than 2 weeks in starting a new cycle was experienced during the first 2 cycles of combination therapy.

Intervention Type: DRUG

Other Intervention Names

lenalidomide; Azacitidine

Eligibility Criteria

Inclusion Criteria

1. ECOG performance status of < 2 at study entry (see Appendix II).

2. 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.

3. Serum bilirubin levels < 1.5 times the upper limit of the normal range for the laboratory (ULN). Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis.

4. Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) levels < 2 x ULN.

5. Serum creatinine levels 1.5 x ULN

6. Absolute neutrophil count > 1000/mm³

7. Platelet count > 30,000/mm³

8. All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.

9. Females of childbearing potential (FCBP)† must have a negative serum or urine

Exclusion Criteria

1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.

2. Pregnant or breast feeding females. Lactating females must agree not to breast feed while taking Revlimid® (lenalidomide).

3. 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.

4. Use of any other experimental drug or therapy within 28 days of baseline.

5. Known hypersensitivity to lenalidomide, azacitidine, or mannitol.

6. Any prior use of Vidaza® (azacitidine).

7. Prior use of Revlimid® (lenalidomide) for more than 84 days (three 28 day cycles).

8. Concurrent use of other anti-cancer agents or treatments.

9. Known positive for HIV or infectious hepatitis, type B or C.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene Corporation

INDUSTRY

Sponsor Role: collaborator

Rush University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Jamile Shammo

Associate Professor of Medicine and Pathology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jamile M Shammo, MD

Role: PRINCIPAL_INVESTIGATOR

Rush University Medical Center

Locations

Rush University Medical Center

Chicago, Illinois, United States

Countries

United States

Other Identifiers

MDS 2008-01

Identifier Type: -

Identifier Source: org_study_id