Antithymocyte Globulin and Sirolimus in Treating Patients With Relapsed Multiple Myeloma

NCT00317798 | Completed Phase 1

• 3 other identifiers: CDR0000480087URCC-U11405GENZ-URCC-U11405
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Biological therapies, such as antithymocyte globulin may stimulate the immune system in different ways and stop cancer cells from growing. Sirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It may also prevent or reduce the side effects of antithymocyte globulin. Giving antithymocyte globulin together with sirolimus may kill more cancer cells. PURPOSE: This phase I trial is studying the side effects and best dose of antithymocyte globulin when given together with sirolimus in treating patients with relapsed multiple myeloma.

Conditions

Drug/Agent Toxicity by Tissue/Organ; Multiple Myeloma and Plasma Cell Neoplasm

Keywords

drug/agent toxicity by tissue/organ; stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; refractory multiple myeloma

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicity and maximum tolerated dose

  Duration of the study

Secondary Outcomes (2)

• Relapse rates as measured by standard response criteria

  Duration of the study

• Laboratory correlative studies

  During treatment

Interventions

anti-thymocyte globulin BIOLOGICAL

Escalating doses of rATG,intravenously, starting at 6 mg/kg to a maximum of 14.5 mg/kg. Rapamycin is given orally, starting at a dose of 1 mg daily beginning on day 1 and terminating on day 30. The dose of rapamycin was adjusted to maintain a constant blood level of 4-6 ng/ml in all subjects

sirolimus DRUG

escalating doses of rATG, intravenously, starting at 6 mg/kg to a maximum of 14.5 mg/kg. Rapamycin is given orally, starting at a dose of 1 mg daily beginning on day 1 and terminating on day 30. The dose of rapamycin was adjusted to maintain a constant blood level of 4-6 ng/ml in all subjects

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Previously diagnosed multiple myeloma (MM) based on standard criteria * Soft tissue (not bone only) plasmacytomas allowed * Measurable disease, meeting both of the following criteria: * Monoclonal population of plasma cell in the bone marrow * Quantifiable serum and/or urine monoclonal protein (i.e., generally, but not exclusively, IgG \> 1 g/dL, IgA \> 0.5 g/dL, or urine light-chain excretion ≥ 200 mg/24 hours) * Steroid-refractory disease, defined as less than a minimum response to prior high-dose glucocorticoid therapy * Minimal response requires all of the following criteria: * 25-49% reduction in the level of serum monoclonal paraprotein maintained for ≥ 6 weeks * 50-89% reduction in 24-hour urinary light-chain excretion, but still \> 200 mg/24 hours, maintained for ≥ 6 weeks * 25-49% reduction in the size of soft tissue plasmacytomas (clinically or by CT scan or MRI) * No increase in size or number of lytic bone lesions * High-dose glucocorticoid therapy defined as 480 mg dexamethasone (or equivalent) alone or as part of a vincristine, doxorubicin, and dexamethasone regimen * Must have undergone autologous transplantation OR received ≥ 2 conventional lines of therapy * Currently requiring therapy for progressive disease, as indicated by any of the following criteria: * 25% increase in paraprotein * Development of new or progression of pre-existing lytic bone lesions or soft tissue plasmacytomas * Hypercalcemia not attributable to any other cause * Relapse from complete remission * No nonsecretory MM PATIENT CHARACTERISTICS: * Zubrod performance status 0-2 * 3-4 allowed if, in the opinion of the investigator, secondary to MM-related bone pain * Life expectancy ≥ 3 months * Creatinine ≤ 1.5 times upper limit of normal (ULN) * AST and ALT ≤ 2.5 times ULN * Bilirubin ≤ 1.5 times ULN * Calcium \< 14 mg/dL * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * HIV negative * Hepatitis B surface antigen and hepatitis C antibody negative * No known history of allergy to rabbit proteins * No history of cardiac amyloidosis * No poorly controlled hypertension, diabetes mellitus, coronary artery disease, or other serious medical or psychiatric illness * No myocardial infarction within the past 6 weeks * No New York Heart Association class III or IV heart failure * No uncontrolled angina * No severe uncontrolled ventricular arrhythmias * No evidence of acute ischemia or active conduction system abnormality by electrocardiogram * No active systemic infection requiring treatment unless adequately controlled with appropriate antimicrobial therapy (e.g., treated central line infection) * No acute viral illness * No pathologic fractures or symptomatic hyperviscosity * No other prior malignancy except adequately treated basal cell or squamous cell skin cancer, cervical cancer in situ, or any other cancer with a disease-free status for ≥ 3 years PRIOR CONCURRENT THERAPY: * See Disease Characteristics * At least 8 weeks since prior immunotherapy or antibody therapy * At least 4 weeks since prior major surgery (except for kyphoplasty) * At least 3 weeks since prior conventional chemotherapy or radiotherapy for MM * At least 3 weeks since prior bortezomib, thalidomide, or clarithromycin for MM * No prior anti-thymocyte globulin * No concurrent radiotherapy * No other concurrent antineoplastic therapy with known activity against MM, including clarithromycin * No other concurrent investigational agents

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of Rochester: lead

Study Sites (1)

James P. Wilmot Cancer Center at University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

MeSH Terms

Conditions

Drug-Related Side Effects and Adverse Reactions; Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Antilymphocyte Serum; Sirolimus

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Macrolides; Lactones; Organic Chemicals

Study Officials

• J. J. Ifthikharuddin, MD

  James P. Wilmot Cancer Center

  PRINCIPAL INVESTIGATOR

• Martin S. Zand, MD, PhD

  James P. Wilmot Cancer Center

  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: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 24, 2006
• First Posted: April 25, 2006
• Study Start: April 1, 2006
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2011
• Last Updated: August 30, 2011

Record last verified: 2011-08

Locations

US (1)