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

NCT01034592 | Terminated Phase 1 Results DMC FDA Drug

• 4 other identifiers: IRB-16822SU-12082009-4523RV-0365HEMMDS0022
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  6 months

Secondary Outcomes (6)

• Red Blood Cell (RBC) Transfusions

  6 months

• Hemoglobin Concentration

  6 months

• Neutrophil Response

  6 months

• Platelet Response

  6 months

• Duration of Response

  6 months

Study Arms (1)

Lenalidomide

EXPERIMENTAL

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.

Drug: Lenalidomide

Interventions

Lenalidomide DRUG

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

Also known as: Revlimid, CC-5013

Lenalidomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jason Robert Gotlib: lead
• Celgene Corporation: collaborator

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Anemia; Leukemia; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Lenalidomide

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Histologic Type; Neoplasms; Leukemia, Myeloid; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Only 2 subjects were enrolled on this protocol. Low accrual was related to various factors. Given the accrual status, no substantive conclusions about the efficacy or safety of lenalidomide in adults with Diamond-Blackfan Anemia could be reached.

Results Point of Contact

• Title: Jason R Gotlib, MD, Professor of Medicine (Hematology)
• Organization: Stanford University Medical Center

jason.gotlib@stanford.edu

650-867-2823

Study Officials

• Jason Robert Gotlib

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof-Med Ctr Line in Medicine

Study Record Dates

• First Submitted: December 15, 2009
• First Posted: December 17, 2009
• Study Start: November 1, 2009
• Primary Completion: October 1, 2012
• Study Completion: December 1, 2012
• Last Updated: August 2, 2017
• Results First Posted: February 7, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)