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

NCT ID: NCT01034592

Last Updated: 2017-08-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2012-12-31

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Lenalidomide

Intervention Type: DRUG

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

Interventions

Lenalidomide

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

Intervention Type: DRUG

Other Intervention Names

Revlimid; CC-5013

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene Corporation

INDUSTRY

Sponsor Role: collaborator

Jason Robert Gotlib

OTHER

Sponsor Role: lead

Responsible Party

Jason Robert Gotlib

Prof-Med Ctr Line in Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jason Robert Gotlib

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University School of Medicine

Stanford, California, United States

Countries

United States

Other Identifiers

SU-12082009-4523

Identifier Type: OTHER

Identifier Source: secondary_id

RV-0365

Identifier Type: OTHER

Identifier Source: secondary_id

HEMMDS0022

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-16822

Identifier Type: -

Identifier Source: org_study_id