Pilot Lenalidomide in Adult Diamond-Blackfan Anemia Patients w/ RBC Transfusion-Dependent Anemia

• ClinicalTrials.gov Identifier: NCT01034592
• Recruitment Status: Terminated
• First Posted: December 17, 2009
• Results First Posted: February 7, 2017
• Last Update Posted: August 2, 2017
• Sponsor: Jason Robert Gotlib
• Collaborator: Celgene Corporation
• Information provided by (Responsible Party): Jason Robert Gotlib, Stanford University

Tracking Information

• First Submitted Date: December 15, 2009
• First Posted Date: December 17, 2009
• Results First Submitted Date: December 13, 2016
• Results First Posted Date: February 7, 2017
• Last Update Posted Date: August 2, 2017
• Study Start Date: November 2009
• Actual Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 22, 2017)

Red Blood Cell (RBC) Transfusion Independence [ Time Frame: 6 months ]

Red blood cell (RBC) transfusion independence is reported as the number of subjects who achieve a continuous absence of the intravenous infusion of any RBC transfusion during any consecutive "rolling" 56 days during the treatment period.

• Original Primary Outcome Measures (submitted: December 15, 2009): RBC Transfusion Independence [ Time Frame: Assessment done every 56 days: D56, D112, D168, D224, then every month during Maintenance Phase ]

Current Secondary Outcome Measures (submitted: March 22, 2017)

• Red Blood Cell (RBC) Transfusions [ Time Frame: 6 months ]
  The effect on red blood cell (RBC) transfusions was assessed as the number of participants that achieved a greater than 50% decrease in RBC transfusion requirements.
• Hemoglobin Concentration [ Time Frame: 6 months ]
  The effect on hemoglobin concentration was assessed as the change from baseline, measured in g/dL.
• Neutrophil Response [ Time Frame: 6 months ]
  The effect on neutrophil levels was assessed as the change in neutrophil count from baseline.
• Platelet Response [ Time Frame: 6 months ]
  The effect on platelet levels as assessed as the change in platelet count from baseline.
• Duration of Response [ Time Frame: 6 months ]
  The response duration was measured from the last of the consecutive 56 days during which the subject was free of red blood cells (RBC) transfusions to the date of the first RBC transfusion after the 56-day RBC-transfusion-free period.
• Toxicity [ Time Frame: 6 months ]
  Toxicity was assessed as the number of adverse events related to lenalidomide.

Original Secondary Outcome Measures (submitted: December 15, 2009)

• >50% Decrease in RBC Transfusion Requirements [ Time Frame: Assessment done every 56 days: D56, D112, D168, D224, then every month during Maintenance Phase ]
• Change of Hemoglobin Concentration From Baseline [ Time Frame: Assessed weekly up to end of cycle 8 (Day 224) or Early Discontinuation, then every two weeks during Maintenance Phase with an additional assessment done 30 days (+/- 3 days) after last dose of study drug ]
• Neutrophil Response [ Time Frame: Assessed weekly up to end of cycle 8 (Day 224) or Early Discontinuation, then every two weeks during Maintenance Phase with an additional assessment done 30 days (+/- 3 days) after last dose of study drug ]
• Platelet Response [ Time Frame: Assessed weekly up to end of cycle 8 (Day 224) or Early Discontinuation, then every two weeks during Maintenance Phase with an additional assessment done 30 days (+/- 3 days) after last dose of study drug ]
• Bone Marrow Response [ Time Frame: End of cycle 8 (Day 224) or Early Discontinuation, then every 6 months during Maintenance Phase ]
• Duration of Response [ Time Frame: Day 56 and end of cycle 8 (Day 224) or Early Discontinuation, then every month during Maintenance Phase ]
• Safety (Type, Frequency, Severity, and Relationship of Adverse Events to Lenalidomide) [ Time Frame: Safety is monitored on a continuous basis throughout the trial period, and for 30 days after last dose of study medication ]
• Correction of Clinical Response With Ribosomal Protein Mutation Status and ex Vivo Effects of Lenalidomide on Marrow Erythroid Colony Growth and Microarray Gene Expression Signatures [ Time Frame: Assessment done end of cycle 8 (Day 224) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pilot Lenalidomide in Adult Diamond-Blackfan Anemia Patients w/ RBC Transfusion-Dependent Anemia
• Official Title: A Pilot Study of Lenalidomide in Adult Diamond-Blackfan Anemia Patients With Red Blood Cell Transfusion-Dependent Anemia

Brief Summary

This is a single-center, single arm, open-label study of oral lenalidomide monotherapy administered to red blood cell (RBC) transfusion dependent adult subjects with Diamond-Blackfan Anemia (DBA).

Primary Objective: To evaluate the erythroid response rate as measured by rate of red blood cell transfusion independence [MDS International Working Group (IWG) 2000 Criteria will be applied].

Secondary Objective: 1)To evaluate the tolerability and safety profile of lenalidomide in patients with DBA and other inherited marrow failure syndromes 2) To correlate response to lenalidomide with biologic surrogates of DBA including ribosomal protein mutation status, ex vivo erythroid colony growth, and microarray gene expression

• Detailed Description: This pilot study will utilize an intra-patient dose escalation design. Cycles are 28 days in length. Subjects will receive lenalidomide 2.5 mg weekly during days 1 to 21 of cycle 1 (dose level 1). If patients do not experience any grade > 3 hematologic or non-hematologic toxicity, the dose will be increased to 2.5 mg twice weekly on days 1 to 21 of cycle 2 (dose level 2). If patients do not experience any grade > 3 hematologic or non-hematologic toxicity, the dose will be increased to 5 mg twice weekly on days 1 to 21 of cycle 3 (dose level 3). If patients do not experience any grade >3 hematologic or non-hematologic toxicity, the dose will be increased to 5 mg thrice weekly on days 1 to 21 of cycle 4 (dose level 4). Patients who experience grade >3 hematologic or non-hematologic toxicity at dose level 1 will be discontinued from study. Patients who experience grade > 3 hematologic or non-hematologic toxicity at dose level 2, 3, or 4 will have the lenalidomide held and dose reduced according to protocol dose interruption/modification algorithms (section 5.5.3). If at least a minor erythroid response is not achieved at the end of 8 cycles of treatment, patients will be discontinued from study. If a minor or major erythroid response is achieved after completion of 8 cycles of treatment, patients can continue study drug on a maintenance phase until loss of erythroid response (return to baseline hemoglobin or transfusion requirement) or unacceptable toxicity.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Anemia
• Leukemia
• Acute Myeloid Leukemia (AML)
• Myelodysplastic Syndromes (MDS)

Intervention

Drug: Lenalidomide

2.5 mg/wk up to 5 mg 3x/wk

Other Names:

• Revlimid
• CC-5013

Study Arms

Experimental: Lenalidomide

Subjects will initially receive lenalidomide 2.5 mg, and may escalate up to 2.5 mg/wk up to 5 mg 3x/wk, depending toxicity and response.

Intervention: Drug: Lenalidomide

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: December 13, 2016): 2
• Original Estimated Enrollment (submitted: December 15, 2009): 11
• Actual Study Completion Date: December 2012
• Actual Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

INCLUSION CRITERIA

• Understand and voluntarily sign an informed consent form
• Diagnosis of DBA
• Age ≥ 18 years at the time of signing the informed consent form.
• Able to adhere to the study visit schedule and other protocol requirements.
• Red blood cell transfusion-dependent with a requirement of at least one unit of RBCs per month for the 2 months prior to study enrollment (eg, 2 units/8 weeks)
• If applicable, ongoing therapy with a stable or decreasing dose of prednisone ≤ 60 mg/d or corticosteroid equivalent, for which there has been no treatment-related improvement in RBC transfusion requirements for at least 2 months prior to study entry
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 at study entry.

• Laboratory test results within these ranges:

  • Absolute neutrophil count (ANC) ≥ 1500/uL
  • Platelet (Plt) count ≥ 100,000/uL
  • Serum creatinine ≤ 2.0 mg/dL
  • Direct bilirubin ≤ 1.5 mg/dL
  • Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) ≤ 2.5 x ULN
  • Disease-free of prior malignancies for ≥ 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in-situ" of the cervix or breast
• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of ≥ 50 milli-International Units (MIU)/mL within 10 to 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 2 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
• Able to take aspirin (81 to 325 mg) daily as prophylactic anticoagulation (patients intolerant to aspirin may use warfarin or low molecular weight heparin)

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 (excluding steroids) specifically used for DBA within 28 days of baseline including metoclopramide, leucine, danazol, or other hormonal therapy
• Clinically significant anemia due to factors such as iron, B12, folate deficiencies, autoimmune or hereditary hemolysis, or gastrointestinal bleeding.
• 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
• Concurrent use of other anti-cancer agents or treatments
• Known positive for HIV or infectious hepatitis, type A, B or C

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01034592
• Other Study ID Numbers: IRB-16822; SU-12082009-4523 ( Other Identifier: Stanford University ); RV-0365 ( Other Identifier: Celgene Corporation ); HEMMDS0022 ( Other Identifier: OnCore )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Jason Robert Gotlib, Stanford University
• Study Sponsor: Jason Robert Gotlib
• Collaborators: Celgene Corporation

Investigators

• Principal Investigator: Jason Robert Gotlib; Stanford University

• PRS Account: Stanford University
• Verification Date: June 2017