Immunotherapy Using Lenalidomide + Bystander Vaccine in High Risk Myelodysplastic Syndrome (MDS)

NCT00840931 | Completed Phase 1 DMC

• 5 other identifiers: MCC-14998105861RV-MDS-PI-202BB-IND 134780803-907
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find out the maximum tolerated dose (MTD) of the combined therapy of lenalidomide (Revlimid®) and Granulocyte/macrophage colony stimulating factor and CD40 Ligand expressed in the K562 cell line (GM.CD40L) bystander vaccine. This research is also being done to see how well the combination of these drugs works to fight myelodysplastic syndrome (MDS).

Conditions

Leukemia

Keywords

Myeloid; Monocytic; Immunotherapy; Vaccine; MDS; High Risk Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  Determination of MTD of GM.CD40L bystander vaccine with lenalidomide in high-risk MDS patients.

  24 months

Secondary Outcomes (7)

• Number of Participants with Toxicities

  24 months

• Number of Participants with Augmentation of Specific T Cell Immunological Functions

  24 months

• Number of Participants with Reduction of Bone Marrow Myeloblast

  24 months

• Number of Participants with Improvement of Hemoglobin and/or red blood cell (RBC) Transfusion Independence

  24 months

• Number of Participants with Resolution of Karyotypic Changes

  24 months

Study Arms (1)

Immunotherapy

EXPERIMENTAL

Participants will take two 5 mg capsules of lenalidomide per day for 21 days followed by 7 days of rest. This 28 day period is considered 1 cycle. Participants will receive 4 treatment cycles with 28 days in each cycle. Those participants showing a clinical response after 4 cycles of treatment may continue to receive lenalidomide as a single agent for additional cycles at the treating Physicians discretion. During each 28 day cycle participants will also receive GM.CD40L bystander vaccination injections in 2-week intervals on days 8 and 22 for a total of 8 immunizations during the 4 cycle treatment period.

Drug: lenalidomide; Biological: bystander vaccine

Interventions

lenalidomide DRUG

Patients will take 10 mg capsules of lenalidomide per day for 21 days followed by 7 days of rest. This 28 day period is considered 1 cycle. Patients will receive 4 treatment cycles with 28 days in each cycle.

Also known as: Revlimid®

Immunotherapy

bystander vaccine BIOLOGICAL

In addition to lenalidomide, during each 28 day cycle patients will also receive GM.CD40L bystander vaccination injections in 2-week intervals on days 8 and 22 for a total of 8 immunizations during the 4 cycle treatment period.

Also known as: GM.CD40L

Immunotherapy

Eligibility Criteria

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

You may qualify if:

• Must understand and voluntarily sign an informed consent form
• Age ≥18 years at the time of signing the informed consent form
• Able to comply with the study visit schedule and assessments required by the protocol
• Documented diagnosis of MDS with subtypes of Refractory Anemia with Excess Blast 1 (RAEB-1) (myeloblast ≥5-9%) or Refractory Anemia with Excess Blast 2 (RAEB-2) (myeloblast ≥10-19%) or intermediate 2, Acute myelogenous leukemia with bone marrow myeloblast \>30% and high risk defined by International Prognostic Scoring System (IPSS) scores or refractory anemia with excess blast in transformation (RAEB-t) (myeloblast ≥ 20-30%) as per French-American-British Classification System (FAB) criteria. Any single or combination of cytogenetic abnormalities is allowed.
• Study treatment can be offered as first line treatment as long as the available food and Drug Administration (FDA) approved treatment options are explained by the treating physician and the participant declines such options.
• Study treatment can be offered to patients who have failed, cannot tolerate or do not wish to continue other therapeutic agents for MDS.
• Prior chemotherapy is allowed but should be off chemotherapy of any kind for at last 4 weeks prior to initiation of study therapy.
• Must be able to provide adequate bone marrow (BM) aspirate and biopsy specimens for histopathological evaluation, cytogenetic analysis and tissue banking during the screening procedure.
• Platelet count must be \> 20,000/ µl without platelet transfusion.
• Absolute neutrophil count (ANC) must be \>500/ µl without myeloid growth factor support.
• Should not be receiving erythropoietin and/or myeloid growth factor for at least 14 days prior to initiation of study therapy.
• Should not have current diagnosis or prior history of any autoimmune or immune deficiency disorders including human immunodeficiency virus positive/acquired immunodeficiency syndrome (HIV+/AIDS).
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 14 days prior to and again within 24 hours of starting lenalidomide 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. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
• Both male and female and members of all races and ethnic groups are eligible for this study.

You may not qualify if:

• Prior therapy with lenalidomide.
• Proliferative chronic myelomonocytic leukemia (CMML with WBC≥12,000/µL in peripheral blood), confirmed by bone marrow biopsy.
• Acute myelogenous leukemia with bone marrow myeloblast ≥30%
• MDS secondary to treatment with radiotherapy, chemotherapy, and/or immunotherapy for malignant or autoimmune diseases are excluded.
• Any of the following laboratory abnormalities:
• Serum creatinine \> 1.5 x upper limit of normal (ULN)
• Serum aspartic transaminase (AST) or alanine transaminase (ALT) \>2.0 x ULN
• Serum total bilirubin \> 2.0 mg/dL (34 µmol/L)
• Prior ≥ grade-2 national Cancer Institute Common Toxicity Criteria (NCI CTC) allergic reaction to thalidomide.
• Prior desquamating (blistering) rash while taking thalidomide.
• Prior allergic reaction to vaccination of any sort.
• Participants with ≥ grade-2 neuropathy.
• Clinically significant anemia due to factors such as iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis or gastrointestinal bleeding.
• Use of cytotoxic chemotherapeutic agents, growth factors, or experimental agents (agents that are not commercially available) for the treatment of MDS within 28 days of the start of drug treatment.
• Prior history of malignancy other than MDS (except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix) unless the participant has been free of disease for ≥3 years.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Celgene: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Leukemia

Interventions

Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic 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

Study Officials

• Javier Pinilla, M.D., Ph.D.

  H. Lee Moffitt Cancer & Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2009
• First Posted: February 11, 2009
• Study Start: February 2, 2009
• Primary Completion: February 17, 2014
• Study Completion: December 1, 2019
• Last Updated: December 11, 2019

Record last verified: 2019-12

Locations

US (1)