Trial of High Dose Lenalidomide in Patients With MDS and AML With Trilineage Dysplasia

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00867308
• Collaborator: (none)
• Enrollment: 32
• Location: 1
• Arms: 2
• Actual Duration (Months): 58
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This is a phase II study of lenalidomide in patients with myelodysplastic syndrome (MDS) and with acute myeloid leukemia (AML) with trilineage dysplasia. Patients will receive two cycles of lenalidomide. Patients who respond may given additional cycles of lenalidomide until disease progression.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndrome	Drug: Lenalidomide 50 mg; Drug: Lenalidomide 15 mg	Phase 2

Detailed Description

This is a single center open label phase II study of lenalidomide in IPSS Int-1 with increased blasts or hematologic needs with 5q31.1 deletions who have failed to respond to standard dose lenalidomide., IPSS Int-1 with increased blasts or hematologic needs without 5q31.1 deletions, and Int-2 and high risk myelodysplastic syndrome (MDS) patients with or without 5q31.1 deletions, regardless of whether they have received lenalidomide previously or not. Patients will receive two cycles of 15 mg daily lenalidomide (later amended to 50 mg daily lenalidomide) given on days 1-28 out of a 42 day cycle. Within each of the two cycles of lenalidomide, patients will be given up to three weeks with no drug treatment to recover. Patients who fail to respond after two cycles of treatment may receive two additional cycles if stable. Patients who develop clinical response may continue to receive drug until disease progression.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of High Dose Lenalidomide in Patients With MDS and AML With Trilineage Dysplasia (AML-TLD)
• Actual Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lenalidomide 15 mg Patients diagnosed with high risk Myelodysplastic syndrome (MDS), regardless of 5q deletion status, will receive lenalidomide 15 mg per day orally, on days 1-28 of a 42 day cycle for 2 cycles. At this point, patients meeting protocol specified response criteria will proceed to Continuing Therapy on a reduced dose of lenalidomide until progression. Patients not achieving response will receive 2 additional cycles of treatment, whereupon response will again be assessed. Patients achieving response at this point will proceed to Continuing Therapy as described. Patients without evidence of response after 4 cycles will be taken off-study.	Drug: Lenalidomide 15 mg; Other Names: Revlimid
Experimental: Lenalidomide 50 mg Patients diagnosed with high risk Myelodysplastic syndrome (MDS), regardless of 5q deletion status, will receive lenalidomide 50 mg per day orally, on days 1-28 of a 42 day cycle for 2 cycles. At this point, patients meeting protocol specified response criteria will proceed to Continuing Therapy on a reduced dose of lenalidomide until progression. Patients not achieving response will receive 2 additional cycles of treatment, whereupon response will again be assessed. Patients achieving response at this point will proceed to Continuing Therapy as described. Patients without evidence of response after 4 cycles will be taken off-study.	Drug: Lenalidomide 50 mg; Other Names: Revlimid

Outcome Measures

Primary Outcome Measures

1. Response Rate [15 weeks]

   Number of participants with a complete or partial response according to International Working Group 2006 criteria.

Secondary Outcome Measures

1. Grade 3-4 Toxicity [Up to 8 months]

   Number of participants who experienced at least one grade 3-4 non-hematological toxicity by CTCAE 3.0 that was attributed to lenalidomide.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age greater than 18 years at the time of signing the informed consent form.

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

• MDS or MDS/AML

• Patients must not have received any other treatment for their disease, including hematopoietic growth factors, within three weeks of beginning the trial

• ECOG performance status of 0, 1, or 2 at study entry

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

• Patients must have no clinical evidence of CNS or pulmonary leukostasis, disseminated intravascular coagulation, or CNS leukemia.

• Subjects must agree to use appropriate contraception.

Exclusion Criteria:

• 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 21 days of baseline.

• Known hypersensitivity to thalidomide.

• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.

• Any prior use of lenalidomide except for MDS patients with del 5q31.1 abnormalities..

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

• Patients may not have received prior AML induction chemotherapy or stem cell transplant. However, patients with secondary MDS who have received a stem cell transplant for other indications (eg lymphoma, multiple myeloma) will be eligible.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21205

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Investigators

• Principal Investigator: Amy DeZern, MD, Johns Hopkins University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT00867308
• Other Study ID Numbers: J0882; RV- MDS-PI-295; NA_00019818
• First Posted: Mar 23, 2009
• Last Update Posted: Oct 17, 2018
• Last Verified: Sep 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: IPSS Int-2; high risk myelodysplastic syndrome; MDS); 5q31.1 deletions
• Additional relevant MeSH terms: Preleukemia; Myelodysplastic Syndromes; Lenalidomide

Study Results

Participant Flow

Pre-assignment Detail	2 participants on the 15mg arm and 3 participants on the 50mg arm were screen failures.

Arm/Group Title	Lenalidomide 15 mg	Lenalidomide 50 mg
Arm/Group Description	Patients diagnosed with high risk Myelodysplastic syndrome (MDS), regardless of 5q deletion status, will receive lenalidomide 15 mg per day orally, on days 1-28 of a 42 day cycle for 2 cycles. At this point, patients meeting protocol specified response criteria will proceed to Continuing Therapy on a reduced dose of lenalidomide until progression. Patients not achieving response will receive 2 additional cycles of treatment, whereupon response will again be assessed. Patients achieving response at this point will proceed to Continuing Therapy as described. Patients without evidence of response after 4 cycles will be taken off-study.	Patients diagnosed with high risk Myelodysplastic syndrome (MDS), regardless of 5q deletion status, will receive lenalidomide 50 mg per day orally, on days 1-28 of a 42 day cycle for 2 cycles. At this point, patients meeting protocol specified response criteria will proceed to Continuing Therapy on a reduced dose of lenalidomide until progression. Patients not achieving response will receive 2 additional cycles of treatment, whereupon response will again be assessed. Patients achieving response at this point will proceed to Continuing Therapy as described. Patients without evidence of response after 4 cycles will be taken off-study.
Period Title: Overall Study
STARTED	9	18
COMPLETED	0	0
NOT COMPLETED	9	18

Baseline Characteristics

Arm/Group Title	Lenalidomide 15 mg	Lenalidomide 50 mg	Total
Arm/Group Description	Patients diagnosed with high risk Myelodysplastic syndrome (MDS), regardless of 5q deletion status, will receive lenalidomide 15 mg per day orally, on days 1-28 of a 42 day cycle for 2 cycles. At this point, patients meeting protocol specified response criteria will proceed to Continuing Therapy on a reduced dose of lenalidomide until progression. Patients not achieving response will receive 2 additional cycles of treatment, whereupon response will again be assessed. Patients achieving response at this point will proceed to Continuing Therapy as described. Patients without evidence of response after 4 cycles will be taken off-study.	Patients diagnosed with high risk Myelodysplastic syndrome (MDS), regardless of 5q deletion status, will receive lenalidomide 50 mg per day orally, on days 1-28 of a 42 day cycle for 2 cycles. At this point, patients meeting protocol specified response criteria will proceed to Continuing Therapy on a reduced dose of lenalidomide until progression. Patients not achieving response will receive 2 additional cycles of treatment, whereupon response will again be assessed. Patients achieving response at this point will proceed to Continuing Therapy as described. Patients without evidence of response after 4 cycles will be taken off-study.	Total of all reporting groups
Overall Participants	9	18	27
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	3 33.3%	4 22.2%	7 25.9%
>=65 years	6 66.7%	14 77.8%	20 74.1%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	77	70	72
Sex: Female, Male (Count of Participants)
Female	1 11.1%	4 22.2%	5 18.5%
Male	8 88.9%	14 77.8%	22 81.5%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%

Outcome Measures

1. Primary Outcome

Title	Response Rate
Description	Number of participants with a complete or partial response according to International Working Group 2006 criteria.
Time Frame	15 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lenalidomide 15 mg	Lenalidomide 50 mg
Arm/Group Description	Patients diagnosed with high risk Myelodysplastic syndrome (MDS), regardless of 5q deletion status, will receive lenalidomide 15 mg per day orally, on days 1-28 of a 42 day cycle for 2 cycles. At this point, patients meeting protocol specified response criteria will proceed to Continuing Therapy on a reduced dose of lenalidomide until progression. Patients not achieving response will receive 2 additional cycles of treatment, whereupon response will again be assessed. Patients achieving response at this point will proceed to Continuing Therapy as described. Patients without evidence of response after 4 cycles will be taken off-study.	Patients diagnosed with high risk Myelodysplastic syndrome (MDS), regardless of 5q deletion status, will receive lenalidomide 50 mg per day orally, on days 1-28 of a 42 day cycle for 2 cycles. At this point, patients meeting protocol specified response criteria will proceed to Continuing Therapy on a reduced dose of lenalidomide until progression. Patients not achieving response will receive 2 additional cycles of treatment, whereupon response will again be assessed. Patients achieving response at this point will proceed to Continuing Therapy as described. Patients without evidence of response after 4 cycles will be taken off-study.
Measure Participants	9	18
Complete response	0 0%	0 0%
Partial response	0 0%	2 11.1%

2. Secondary Outcome

Title	Grade 3-4 Toxicity
Description	Number of participants who experienced at least one grade 3-4 non-hematological toxicity by CTCAE 3.0 that was attributed to lenalidomide.
Time Frame	Up to 8 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lenalidomide 15 mg	Lenalidomide 50 mg
Arm/Group Description	Patients diagnosed with high risk Myelodysplastic syndrome (MDS), regardless of 5q deletion status, will receive lenalidomide 15 mg per day orally, on days 1-28 of a 42 day cycle for 2 cycles. At this point, patients meeting protocol specified response criteria will proceed to Continuing Therapy on a reduced dose of lenalidomide until progression. Patients not achieving response will receive 2 additional cycles of treatment, whereupon response will again be assessed. Patients achieving response at this point will proceed to Continuing Therapy as described. Patients without evidence of response after 4 cycles will be taken off-study.	Patients diagnosed with high risk Myelodysplastic syndrome (MDS), regardless of 5q deletion status, will receive lenalidomide 50 mg per day orally, on days 1-28 of a 42 day cycle for 2 cycles. At this point, patients meeting protocol specified response criteria will proceed to Continuing Therapy on a reduced dose of lenalidomide until progression. Patients not achieving response will receive 2 additional cycles of treatment, whereupon response will again be assessed. Patients achieving response at this point will proceed to Continuing Therapy as described. Patients without evidence of response after 4 cycles will be taken off-study.
Measure Participants	9	18
Count of Participants [Participants]	6 66.7%	12 66.7%

Adverse Events

Time Frame	Up to 8 months
Adverse Event Reporting Description	Due to significant cytopenias in all participants at presentation and throughout the trial, hematologic toxicity was only reported where bone marrow aplasia lasted for >3 weeks from last dose of lenalidomide with a bone marrow cellularity of <5% without evidence of leukemia. Adverse events were collected weekly throughout the trial.
Arm/Group Title	Lenalidomide 15 mg		Lenalidomide 50 mg
Arm/Group Description	Patients diagnosed with high risk Myelodysplastic syndrome (MDS), regardless of 5q deletion status, will receive lenalidomide 15 mg per day orally, on days 1-28 of a 42 day cycle for 2 cycles. At this point, patients meeting protocol specified response criteria will proceed to Continuing Therapy on a reduced dose of lenalidomide until progression. Patients not achieving response will receive 2 additional cycles of treatment, whereupon response will again be assessed. Patients achieving response at this point will proceed to Continuing Therapy as described. Patients without evidence of response after 4 cycles will be taken off-study.		Patients diagnosed with high risk Myelodysplastic syndrome (MDS), regardless of 5q deletion status, will receive lenalidomide 50 mg per day orally, on days 1-28 of a 42 day cycle for 2 cycles. At this point, patients meeting protocol specified response criteria will proceed to Continuing Therapy on a reduced dose of lenalidomide until progression. Patients not achieving response will receive 2 additional cycles of treatment, whereupon response will again be assessed. Patients achieving response at this point will proceed to Continuing Therapy as described. Patients without evidence of response after 4 cycles will be taken off-study.
All Cause Mortality
	Lenalidomide 15 mg		Lenalidomide 50 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/9 (33.3%)		2/18 (11.1%)
Serious Adverse Events
	Lenalidomide 15 mg		Lenalidomide 50 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/9 (33.3%)		9/18 (50%)
Cardiac disorders
Hypotension	0/9 (0%)	0	1/18 (5.6%)	1
General disorders
Epistaxis	1/9 (11.1%)	1	0/18 (0%)	0
Infections and infestations
Clostridium difficile infection	0/9 (0%)	0	1/18 (5.6%)	1
Endocarditis	1/9 (11.1%)	1	0/18 (0%)	0
Febrile neutropenia	1/9 (11.1%)	1	1/18 (5.6%)	1
Fungal pneumonia	0/9 (0%)	0	1/18 (5.6%)	1
Meningitis	1/9 (11.1%)	1	0/18 (0%)	0
Pericarditis	0/9 (0%)	0	1/18 (5.6%)	1
Pneumonia	0/9 (0%)	0	3/18 (16.7%)	3
Nervous system disorders
Weakness - leg	1/9 (11.1%)	1	0/18 (0%)	0
Renal and urinary disorders
Acute kidney injury	0/9 (0%)	0	1/18 (5.6%)	1
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/9 (11.1%)	1	1/18 (5.6%)	1
Other (Not Including Serious) Adverse Events
	Lenalidomide 15 mg		Lenalidomide 50 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/9 (77.8%)		13/18 (72.2%)
Blood and lymphatic system disorders
Bleeding	3/9 (33.3%)	3	3/18 (16.7%)	5
Bruising	0/9 (0%)	0	3/18 (16.7%)	3
Epistaxis	4/9 (44.4%)	5	3/18 (16.7%)	3
Cardiac disorders
Atrial fibrillation	0/9 (0%)	0	2/18 (11.1%)	2
Edema	1/9 (11.1%)	1	7/18 (38.9%)	10
Lightheadedness	0/9 (0%)	0	2/18 (11.1%)	2
Gastrointestinal disorders
Constipation	1/9 (11.1%)	1	6/18 (33.3%)	8
Diarrhea	1/9 (11.1%)	1	4/18 (22.2%)	7
Nausea	1/9 (11.1%)	1	1/18 (5.6%)	1
Stomatitis	1/9 (11.1%)	1	3/18 (16.7%)	3
Vomiting	0/9 (0%)	0	3/18 (16.7%)	3
Xerostomia	0/9 (0%)	0	2/18 (11.1%)	2
General disorders
Anorexia	1/9 (11.1%)	1	4/18 (22.2%)	4
Cough	3/9 (33.3%)	3	4/18 (22.2%)	4
Fatigue	5/9 (55.6%)	5	8/18 (44.4%)	12
Headache	1/9 (11.1%)	2	1/18 (5.6%)	1
Hoarseness	0/9 (0%)	0	2/18 (11.1%)	2
Myalgia	0/9 (0%)	0	6/18 (33.3%)	11
Pain - back	0/9 (0%)	0	2/18 (11.1%)	2
Pain - chest	1/9 (11.1%)	1	1/18 (5.6%)	1
Pain - tooth	0/9 (0%)	0	2/18 (11.1%)	2
Infections and infestations
Febrile neutropenia	3/9 (33.3%)	3	1/18 (5.6%)	1
Fever	1/9 (11.1%)	2	2/18 (11.1%)	2
Thrush	1/9 (11.1%)	1	1/18 (5.6%)	2
Investigations
Anemia	2/9 (22.2%)	2	0/18 (0%)	0
Hyperbilirubinemia	2/9 (22.2%)	2	1/18 (5.6%)	1
Hypokalemia	1/9 (11.1%)	1	1/18 (5.6%)	1
Hyponatremia	1/9 (11.1%)	1	0/18 (0%)	0
Leukopenia	2/9 (22.2%)	2	0/18 (0%)	0
Thrombocytopenia	3/9 (33.3%)	3	0/18 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/9 (0%)	0	2/18 (11.1%)	2
Nervous system disorders
Confusion	1/9 (11.1%)	1	1/18 (5.6%)	1
Hallucination	0/9 (0%)	0	2/18 (11.1%)	2
Neuropathy	0/9 (0%)	0	2/18 (11.1%)	2
Weakness	0/9 (0%)	0	6/18 (33.3%)	6
Renal and urinary disorders
Hematuria	0/9 (0%)	0	2/18 (11.1%)	2
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/9 (11.1%)	1	3/18 (16.7%)	3
Skin and subcutaneous tissue disorders
Pruritis	1/9 (11.1%)	2	8/18 (44.4%)	13
Rash	3/9 (33.3%)	5	6/18 (33.3%)	9
Xerosis	0/9 (0%)	0	2/18 (11.1%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.