Thymoglobulin and Cyclosporine in Patients With Aplastic Anemia or Myelodysplastic Syndrome

NCT00806598 | Completed Phase 2 Results

• 1 other identifier: 2005-0115
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if combining the drugs thymoglobulin, methylprednisolone, cyclosporine, and G-CSF (NeupogenTM or NeulastaTM ) can help to control severe aplastic anemia (AA) or hypoplastic myelodysplastic syndrome (MDS). The safety of this combination therapy will also be studied.

Conditions

Myelodysplastic Syndrome; Aplastic Anemia

Keywords

Myelodysplastic Syndrome; Aplastic Anemia; Thymoglobulin; Cyclosporine; Methylprednisolone; G-CSF

Outcome Measures

Primary Outcomes (1)

• Overall Response

  Complete response (CR) was defined as normalization of peripheral blood and bone marrow with \<5% blasts, a peripheral absolute neutrophil count (ANC) \>/= 1 \* 10\^9/l, hemoglobin \>/= 100g/l, and a platelet count \>/= \* 10\^9/l, Partial Response (PR) was defined as transfusion independence with a peripheral blood ANC \>=/ 0.05 \* 10\^9/l, a platelet count \>/= 20 \* 10\^9/l, and a hemoglobin \>/= 40 g/l. Hematologic improvement was defined as a clinically relevant increase in hemoglobin, platelets or absolute neutrophil count.

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first. Assessed first at 3 months on study, continuing monthly up to 3 years.

Study Arms (1)

Thymoglobulin + Cyclosporin

EXPERIMENTAL

Combination of Thymoglobulin 3.5 or 2.5 mg/kg/day intravenous (IV) for 5 days + Methylprednisone 1 mg/kg/day IV for 5 days, before each dose Thymoglobulin + Cyclosporin 5 mg/kg orally for 6 months following Thymoglobulin + Granulocyte - Colony Stimulating Factor (G-CSF) 5 microgram/kg subcutaneously daily up to 3 months

Drug: Thymoglobulin; Drug: Cyclosporine; Drug: Methylprednisolone; Drug: G-CSF

Interventions

Thymoglobulin DRUG

3.5 or 2.5 mg/kg/day IV for 5 days * Aplastic anemia patients receive 3.5 mg/kg/day for 5 days * MDS patients \<55 years receive 3.5 mg/kg/day for 5 days * MDS patients \>55 years receive 2.5 mg/kg/day for 5 days

Also known as: ATG, Antithymocyte globulin

Thymoglobulin + Cyclosporin

Cyclosporine DRUG

5 mg/kg orally for 6 months; start after completing thymoglobulin.

Also known as: CYA, Sandimmune, Cyclosporine A

Thymoglobulin + Cyclosporin

Methylprednisolone DRUG

1 mg/kg/day IV for 5 days, given before each dose of thymoglobulin.

Also known as: Duralone®, Medralone®, Medrol®, M-Prednisol®, Solu-Medrol®

Thymoglobulin + Cyclosporin

G-CSF DRUG

5 microgram/kg subcutaneously daily up to 3 months, start after thymoglobulin.

Also known as: Neupogen®, Granulocyte - Colony Stimulating Factor

Thymoglobulin + Cyclosporin

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of severe aplastic anemia (bone marrow cellularity \< 30%, with two of three peripheral counts at the time of initial presentation or currently low with absolute neutrophil count (ANC) \< 500/mL, pre-transfusion platelet (PLT) \< 20,000/mL, or pre-transfusion hemoglobin \< 8 g/dL and presence of no other underlying disorder.
• Diagnosis of MDS (World Health Organization) with bone marrow cellularity \< 30%, with two of three peripheral counts at the time of initial presentation or currently low with ANC \< 500/mL, pre-transfusion PLT \< 20,000/mL, or pre-transfusion hemoglobin \< 8 g/dL.
• Patients with MDS who have received prior biological therapy (not chemotherapy) are eligible. Hypomethylating agents and histone deacetylase inhibitors are considered as biological therapy.
• Age 15 or greater
• Adequate renal function (creatinine less than or equal to 2.0 mg/dL) unless related to the disease
• Adequate hepatic function (bilirubin less than or equal to 3.5 mg/dL) unless related to the disease
• No other investigational therapy in the past 14 days
• Able to sign consent form
• Able to comply with the need for contraception (abstinence, condom, birth control pill, or other acceptable form of contraception) during the entire study period
• Diagnosis of MDS (WHO) with bone marrow cellularity greater than 30%, with low or intermediate-1 risk by the International Prognostic Scoring System (IPSS) score, and requiring treatment (i.e. transfusion-dependent)

You may not qualify if:

• Active and uncontrolled infection
• HIV positive test
• Pregnant or breast feeding
• Active and uncontrolled medical illness (pulmonary, cardiac, neurological, or other) that in the opinion of treating physician would likely interfere with study treatment

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Official website

MeSH Terms

Conditions

Myelodysplastic Syndromes; Anemia, Aplastic

Interventions

thymoglobulin; Antilymphocyte Serum; Cyclosporine; Methylprednisolone; Methylprednisolone Hemisuccinate; Granulocyte Colony-Stimulating Factor; Filgrastim

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Anemia; Bone Marrow Failure Disorders

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Biological Factors

Results Point of Contact

• Title: Tapan Kadia, MD/Assistant Professor
• Organization: The University of Texas MD Anderson Cancer Center

eharriso@mdanderson.org

713-563-3534

Study Officials

• Tapan M. Kadia, M.D.

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2008
• First Posted: December 11, 2008
• Study Start: May 1, 2005
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: March 12, 2013
• Results First Posted: March 6, 2013

Record last verified: 2013-03

Locations

US (1)