Lenalidomide and Prednisone in Low and Int-1 Myelodysplastic Syndrome (MDS) Non 5q MDS

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01133275
• Collaborator: Celgene Corporation (Industry)
• Enrollment: 28
• Locations: 2
• Arm: 1
• Actual Duration (Months): 114.8
• Patients Per Site: 14
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this research is to evaluate the use of lenalidomide and prednisone in people with Myelodysplastic Syndrome (MDS).

Lenalidomide is a drug that alters the immune system and it may also interfere with the development of tiny blood vessels that help support tumor growth. Therefore, in theory, it may reduce or prevent the growth of cancer cells. Lenalidomide is approved by the U.S. Food and Drug Administration (FDA) for the treatment of specific types of myelodysplastic syndrome (MDS) and in combination with dexamethasone for people with multiple myeloma (MM) who have received at least 1 prior therapy. MDS and MM are cancers of the blood. It is currently being tested in a variety of cancer conditions. As it is being used in this study it is considered an investigational use. An "investigational use" is a use that is being tested and is not approved by the FDA.

Prednisone is approved by the FDA to treat numerous conditions. In addition, prednisone is approved by the FDA to treat Low or Intermediate-1 IPSS Risk, non-del (5q) MDS.

"Study drug" refers to the combination of lenalidomide and prednisone.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndrome; MDS	Drug: Prednisone; Drug: Lenalidomide	Phase 2

Detailed Description

10 mg/day of lenalidomide will be taken by mouth on days 1 - 28 of cycles 1-6. Dosing will be in the morning at approximately the same time each day.

Planned prednisone dose:

• 30 mg by mouth daily, days 1-28 of cycle 1

• 20 mg by mouth daily, days 1-28 of cycle 2

• 10 mg by mouth daily, days 1-28 of cycle 3

• 10 mg by mouth every other day on days 1-28 of cycles 4-6

• 5 mg by mouth every other day for responders beyond cycle 6

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Clinical Trial of Lenalidomide and Prednisone in Low and Intermediate-1 IPSS Risk, Non-del (5q) MDS Patients
• Actual Study Start Date: Apr 28, 2010
• Actual Primary Completion Date: Jan 31, 2015
• Actual Study Completion Date: Nov 21, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lenalidomide and Prednisone Therapy All participants received lenalidomide and prednisone therapy for 6 cycles (24 weeks). Each cycle is 28 days (4 weeks).	Drug: Prednisone; Prednisone therapy for 6 cycles (24 weeks).; Other Names: Deltasone ; Drug: Lenalidomide; Lenalidomide therapy for 6 cycles (24 weeks).; Other Names: REVLIMID®

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Erythroid Response [Up to 7 months]

   The rate of erythroid response to treatment with the lenalidomide/prednisone combination in non-del (5q) low and int-1 risk Myelodysplastic Syndrome (MDS) with symptomatic anemia. Hematological improvement erythroid response (HI-E) according to International Working Group (IWG) 2006 criteria.

Secondary Outcome Measures

1. Number of Participants With Grade 3 or 4 Adverse Events Possibly Related to Treatment [Up to 54 months]

   Grade 3 or 4 events Related/Possibly Related/Probably Related to study treatment. Number of participants with events specified in the study protocol: Neutropenia, Thrombocytopenia, Febrile Neutropenia, Infection, Sepsis, Venous Thromboembolic Events. Evaluations according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V4.0.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Understand and voluntarily sign an informed consent form

• Age ≥ 18 years at the time of signing the informed consent form

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

• Documented diagnosis of MDS according Word Health Organization (WHO) that meets International Prognostic Scoring System (IPSS) criteria for Low- to Intermediate-1-risk disease or non-proliferative (white blood count [WBC] < 13,000/uL) chronic myelomonocytic leukemia (CMML) and MDS/myeloproliferative neoplasms (MPN).

• Absence of a chromosome 5q deletion by metaphase cytogenetics or fluorescent in situ hybridization (FISH) analysis

• Red blood cell (RBC) transfusion-dependent anemia defined as having received ≥4 transfusions of RBCs for hemoglobin (Hgb) ≤ 9.0 g/dl within 56 days of randomization or symptomatic anemia (Hgb ≤ 9.0 g/dl)

• No response or progression on prior treatment with epoetin alpha (> 40,000 U/wk x 6), darbepoetin alpha (≥ 500 mcg q 3 wk x 2) or serum erythropoietin (EPO) concentration ≥ 500 mU/ml

• All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study.

• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 at study entry

• Laboratory test results within these ranges: Absolute neutrophil count ≥ 500 /mm³; Platelet count ≥ 50,000 /mm³; Creatinine Clearance > 60 mL/min by Cockcroft-Gault formula; Total bilirubin ≤ 1.5 mg/dl; aspartic transaminase (AST)and alanine transaminase (ALT) ≤ 2 x upper limit of normal (ULN).

• Disease free of prior malignancies for ≥ 3 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix or breast

• Must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.

• Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 milli-international units per milliliter (mIU/mL) within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.

Exclusion Criteria:

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

• Pregnant or breast feeding. (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

• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs or history of desquamating (blistering) rash while taking thalidomide

• Any prior use of lenalidomide

• Concurrent use of other anti-cancer agents or treatments

• Known positive for human immunodeficiency virus (HIV) or infectious hepatitis, type B or C

• Proliferative CMML (WBC ≥13,000/μL)

• MDS secondary to treatment with radiotherapy, chemotherapy, and/or immunotherapy for malignant or autoimmune diseases

• Prior ≥ grade-2 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) allergic reaction to thalidomide

• Clinically significant anemia due to factors such as iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis or gastrointestinal bleeding

• Known HIV-1 positivity

• Chromosome 5q deletion

• Documented thromboembolic event within the past 3 years

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Florida Shands Cancer Center	Gainesville	Florida	United States	32610
2	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612

Sponsors and Collaborators

• H. Lee Moffitt Cancer Center and Research Institute
• Celgene Corporation

Investigators

• Principal Investigator: Rami Komrokji, M.D., H. Lee Moffitt Cancer Center and Research Institute

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Moffitt Cancer Center Clinical Trials website

Publications

None provided.

• Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• ClinicalTrials.gov Identifier: NCT01133275
• Other Study ID Numbers: MCC-16099; RV-MDS-PI-0456; 25005/1
• First Posted: May 28, 2010
• Last Update Posted: Dec 17, 2019
• Last Verified: Dec 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome; Prednisone; Lenalidomide

Study Results

Participant Flow

Recruitment Details	Participants were recruited at Moffitt Cancer Center and Shands Cancer Hospital at the University of Florida from 4/28/2010 through 8/13/2013.

Arm/Group Title	Lenalidomide and Prednisone Therapy
Arm/Group Description	Lenalidomide and prednisone therapy for 6 cycles (24 weeks). Each cycle is 28 days (4 weeks).
Period Title: Overall Study
STARTED	28
COMPLETED	26
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Lenalidomide and Prednisone Therapy
Arm/Group Description	Lenalidomide and prednisone therapy for 6 cycles (24 weeks). Each cycle is 28 days (4 weeks).
Overall Participants	28
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	8 28.6%
>=65 years	20 71.4%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	68.64
Sex: Female, Male (Count of Participants)
Female	10 35.7%
Male	18 64.3%
Region of Enrollment (participants) [Number]
United States	28 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Erythroid Response
Description	The rate of erythroid response to treatment with the lenalidomide/prednisone combination in non-del (5q) low and int-1 risk Myelodysplastic Syndrome (MDS) with symptomatic anemia. Hematological improvement erythroid response (HI-E) according to International Working Group (IWG) 2006 criteria.
Time Frame	Up to 7 months

Outcome Measure Data

Analysis Population Description

All evaluable participants

Arm/Group Title	Lenalidomide and Prednisone Therapy
Arm/Group Description	Lenalidomide and prednisone therapy for 6 cycles (24 weeks). Each cycle is 28 days (4 weeks).
Measure Participants	26
Number [participants]	5 17.9%

2. Secondary Outcome

Title	Number of Participants With Grade 3 or 4 Adverse Events Possibly Related to Treatment
Description	Grade 3 or 4 events Related/Possibly Related/Probably Related to study treatment. Number of participants with events specified in the study protocol: Neutropenia, Thrombocytopenia, Febrile Neutropenia, Infection, Sepsis, Venous Thromboembolic Events. Evaluations according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V4.0.
Time Frame	Up to 54 months

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	Lenalidomide and Prednisone Therapy
Arm/Group Description	Lenalidomide and prednisone therapy for 6 cycles (24 weeks). Each cycle is 28 days (4 weeks).
Measure Participants	28
Neutropenia	8 28.6%
Thrombocytopenia	4 14.3%
Febrile Neutropenia	0 0%
Infection and Sepsis	0 0%
Venous Thromboembolic Events	0 0%

Adverse Events

Time Frame	4 years, 6 months
Arm/Group Title	Lenalidomide and Prednisone Therapy
Arm/Group Description	Lenalidomide and prednisone therapy for 6 cycles (24 weeks). Each cycle is 28 days (4 weeks).
All Cause Mortality
	Lenalidomide and Prednisone Therapy
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Lenalidomide and Prednisone Therapy
	Affected / at Risk (%)	# Events
Total	8/28 (28.6%)
Blood and lymphatic system disorders
Anemia	1/28 (3.6%)	1
Blood clot	1/28 (3.6%)	1
Cardiac disorders
Myocardial infarction	1/28 (3.6%)	1
Chest pain	1/28 (3.6%)	1
Heart arrhythmia	1/28 (3.6%)	1
Gastrointestinal disorders
Diarrhea	1/28 (3.6%)	1
Rectal bleeding	1/28 (3.6%)	1
Severe abdominal cramping	1/28 (3.6%)	1
Severe nausea	1/28 (3.6%)	1
Uncontrolled vomiting	1/28 (3.6%)	1
Small intestinal blockage	1/28 (3.6%)	1
General disorders
Edema limbs	1/28 (3.6%)	1
Sudden death NOS	1/28 (3.6%)	1
Fever	1/28 (3.6%)	1
Pain - sore throat	1/28 (3.6%)	1
Infections and infestations
Soft tissue infection	1/28 (3.6%)	1
Metabolism and nutrition disorders
Hyponatremia	1/28 (3.6%)	1
Nervous system disorders
Stroke / Cerebrovascular Accident (CVA)	1/28 (3.6%)	1
Psychiatric disorders
Confusion	1/28 (3.6%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/28 (3.6%)	1
Pulmonary hypertension	1/28 (3.6%)	1
Pneumonitis	1/28 (3.6%)	1
Pneumonia	1/28 (3.6%)	1
Other (Not Including Serious) Adverse Events
	Lenalidomide and Prednisone Therapy
	Affected / at Risk (%)	# Events
Total	27/28 (96.4%)
Blood and lymphatic system disorders
Anemia	15/28 (53.6%)	36
Leukocytosis	5/28 (17.9%)	5
Eye disorders
Blurred vision	4/28 (14.3%)	4
Eye disorders - Other	2/28 (7.1%)	2
Gastrointestinal disorders
Diarrhea	13/28 (46.4%)	18
Constipation	6/28 (21.4%)	7
Nausea	5/28 (17.9%)	7
Vomiting	5/28 (17.9%)	5
Abdominal pain	3/28 (10.7%)	3
Gastrointestinal disorders - Other	3/28 (10.7%)	3
Dry mouth	2/28 (7.1%)	3
Dysphagia	2/28 (7.1%)	2
Mucositis oral	2/28 (7.1%)	2
General disorders
Fatigue	13/28 (46.4%)	14
Edema limbs	7/28 (25%)	10
Paul	7/28 (25%)	9
Fever	5/28 (17.9%)	5
Chills	4/28 (14.3%)	4
Infections and infestations
Sinusitis	2/28 (7.1%)	2
Injury, poisoning and procedural complications
Bruising	6/28 (21.4%)	6
Fall	4/28 (14.3%)	4
Investigations
Platelet count decreased	16/28 (57.1%)	37
Neutrophil count decreased	13/28 (46.4%)	49
White blood cell decreased	13/28 (46.4%)	40
Creatinine increased	2/28 (7.1%)	2
Investigations - Other	2/28 (7.1%)	4
Lymphocyte count decreased	2/28 (7.1%)	5
Weight gain	2/28 (7.1%)	3
Metabolism and nutrition disorders
Hyperglycemia	4/28 (14.3%)	4
Hypokalemia	3/28 (10.7%)	4
Metabolism and nutrition disorders - Other	2/28 (7.1%)	6
Musculoskeletal and connective tissue disorders
Generalized muscle weakness	4/28 (14.3%)	4
Musculoskeletal and connective tissue disorder - Other	4/28 (14.3%)	5
Nervous system disorders
Movements involuntary	6/28 (21.4%)	6
Dizziness	4/28 (14.3%)	5
Headache	4/28 (14.3%)	4
Memory impairment	2/28 (7.1%)	2
Peripheral sensory neuropathy	2/28 (7.1%)	3
Sinus pain	2/28 (7.1%)	3
Psychiatric disorders
Insomnia	6/28 (21.4%)	6
Respiratory, thoracic and mediastinal disorders
Dyspnea	6/28 (21.4%)	7
Cough	3/28 (10.7%)	3
Hoarseness	3/28 (10.7%)	3
Nasal congestion	3/28 (10.7%)	3
Allergic rhinitis	2/28 (7.1%)	2
Productive cough	2/28 (7.1%)	2
Respiratory, thoracic and mediastinal disorders - Other	2/28 (7.1%)	2
Skin and subcutaneous tissue disorders
Hyperhidrosis	5/28 (17.9%)	5
Pruritus	5/28 (17.9%)	7
Rash maculo-papular	3/28 (10.7%)	3
Skin and subcutaneous tissue disorders - Other	3/28 (10.7%)	4

Limitations/Caveats

The study was terminated at the end of step one, as no signal of higher response of the combination was observed compared to what was reported on the MDS-002 study.

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.