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

Primary Purpose

Anemia, Leukemia, Acute Myeloid Leukemia (AML)

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Lenalidomide
Sponsored by
Jason Robert Gotlib
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Stanford University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lenalidomide

Arm Description

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.

Outcomes

Primary Outcome Measures

Red Blood Cell (RBC) Transfusion Independence
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.

Secondary Outcome Measures

Red Blood Cell (RBC) Transfusions
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
The effect on hemoglobin concentration was assessed as the change from baseline, measured in g/dL.
Neutrophil Response
The effect on neutrophil levels was assessed as the change in neutrophil count from baseline.
Platelet Response
The effect on platelet levels as assessed as the change in platelet count from baseline.
Duration of Response
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
Toxicity was assessed as the number of adverse events related to lenalidomide.

Full Information

First Posted
December 15, 2009
Last Updated
June 27, 2017
Sponsor
Jason Robert Gotlib
Collaborators
Celgene Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT01034592
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Terminated
Why Stopped
Poor accrual related to rarity of Diamond-Blackfan anemia (DBA)
Study Start Date
November 2009 (undefined)
Primary Completion Date
October 2012 (Actual)
Study Completion Date
December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Jason Robert Gotlib
Collaborators
Celgene Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anemia, Leukemia, Acute Myeloid Leukemia (AML), Myelodysplastic Syndromes (MDS)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lenalidomide
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
Revlimid, CC-5013
Intervention Description
2.5 mg/wk up to 5 mg 3x/wk
Primary Outcome Measure Information:
Title
Red Blood Cell (RBC) Transfusion Independence
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Red Blood Cell (RBC) Transfusions
Description
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.
Time Frame
6 months
Title
Hemoglobin Concentration
Description
The effect on hemoglobin concentration was assessed as the change from baseline, measured in g/dL.
Time Frame
6 months
Title
Neutrophil Response
Description
The effect on neutrophil levels was assessed as the change in neutrophil count from baseline.
Time Frame
6 months
Title
Platelet Response
Description
The effect on platelet levels as assessed as the change in platelet count from baseline.
Time Frame
6 months
Title
Duration of Response
Description
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.
Time Frame
6 months
Title
Toxicity
Description
Toxicity was assessed as the number of adverse events related to lenalidomide.
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jason Robert Gotlib
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University School of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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