A Trial of Lenalidomide & Azacitidine in Low Risk Myelodysplastic Syndromes

• Sponsor: Rush University Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01379274
• Collaborator: Celgene Corporation (Industry)
• Enrollment: 2
• Location: 1
• Arm: 1
• Duration (Months): 34
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
MDS	Drug: Lenalidomide and azacitidine combination	Phase 2

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.

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

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

3. 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.

4. 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.

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

6. Serum creatinine levels < 1.5 x ULN

7. Absolute neutrophil count > 1000/mm³

8. Platelet count > 30,000/mm³

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Revlimid® (Lenalidomide) and Low Dose Vidaza® (Azacitidine) in Patients With Low - Intermediate-1 Risk Myelodysplastic Syndromes
• Study Start Date: Jan 1, 2011
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Nov 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

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

Drug: 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.; Other Names: lenalidomide Azacitidine

Outcome Measures

Primary Outcome Measures

1. Safety and Tolerability of Revlimid and Azacitidine Combination [Study was closed and outcome unable to be measured.]

   To determine the number of subjects who develop grade 4 toxicity while on combination therapy.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria: Patients with low to Int-1 risk MDS

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rush University Medical Center	Chicago	Illinois	United States	60612

Sponsors and Collaborators

• Rush University Medical Center
• Celgene Corporation

Investigators

• Principal Investigator: Jamile M Shammo, MD, Rush University Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jamile Shammo, Associate Professor of Medicine and Pathology, Rush University Medical Center
• ClinicalTrials.gov Identifier: NCT01379274
• Other Study ID Numbers: MDS 2008-01
• First Posted: Jun 23, 2011
• Last Update Posted: Nov 19, 2020
• Last Verified: Nov 1, 2020

• Keywords provided by Jamile Shammo, Associate Professor of Medicine and Pathology, Rush University Medical Center: MDS; Low risk disease; IPSS
• Additional relevant MeSH terms: Preleukemia; Myelodysplastic Syndromes; Lenalidomide; Azacitidine

Study Results

Participant Flow

Recruitment Details	Recruitment from approximately 2010-2012.

Arm/Group Title	Lenalidomide and Azacitidine Combination
Arm/Group Description	Lenalidomide and azacitidine combination to be utilized in patients who did not respond to 3 months of lenalidomide monotherapy. 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.
Period Title: Overall Study
STARTED	2
COMPLETED	1
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Lenalidomide and Azacitidine Combination
Arm/Group Description	Lenalidomide and azacitidine combination to be utilized in patients who did not respond to 3 months of lenalidomide monotherapy. 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.
Overall Participants	2
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	0 0%
>=65 years	2 100%
Sex: Female, Male (Count of Participants)
Female	1 50%
Male	1 50%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (Count of Participants)
United States	2 100%

Outcome Measures

1. Primary Outcome

Title	Safety and Tolerability of Revlimid and Azacitidine Combination
Description	To determine the number of subjects who develop grade 4 toxicity while on combination therapy.
Time Frame	Study was closed and outcome unable to be measured.

Outcome Measure Data

Analysis Population Description

Study was unable to be completed since funding was withdrawn.

Arm/Group Title	Lenalidomide and Azacitidine Combination
Arm/Group Description	Lenalidomide and azacitidine combination to be utilized in patients who did not respond to 3 months of lenalidomide monotherapy. 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.
Measure Participants	0

Adverse Events

Time Frame	Study ended early. Data not analyzed.
Adverse Event Reporting Description	Study ended early. Data not analyzed.
Arm/Group Title	Lenalidomide and Azacitidine Combination
Arm/Group Description	Lenalidomide and azacitidine combination to be utilized in patients who did not respond to 3 months of lenalidomide monotherapy. 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.
All Cause Mortality
	Lenalidomide and Azacitidine Combination
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Lenalidomide and Azacitidine Combination
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Lenalidomide and Azacitidine Combination
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

Study was not able to be completed since funding was withdrawn.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.