Antithymocyte Globulin and Sirolimus in Treating Patients With Relapsed Multiple Myeloma
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|ClinicalTrials.gov Identifier: NCT00317798|
Recruitment Status : Completed
First Posted : April 25, 2006
Last Update Posted : August 30, 2011
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.
|Condition or disease||Intervention/treatment||Phase|
|Drug/Agent Toxicity by Tissue/Organ Multiple Myeloma and Plasma Cell Neoplasm||Biological: anti-thymocyte globulin Drug: sirolimus||Phase 1|
- Determine the safety and tolerability, in terms of clinical and laboratory toxicity, of anti-thymocyte globulin (ATG) combined with sirolimus in patients with relapsed multiple myeloma.
- Determine the dose-limiting toxicity of this regimen in these patients.
- Determine the maximum tolerated dose of ATG when administered with sirolimus in these patients.
- Determine the clinical activity of this regimen, in terms of measurability of improvement in clinical benefits, in these patients.
- Assess patients for sensitivity of CD 138^-positive myeloma cells to ATG prior to treatment.
- Determine the pharmacokinetics, in terms of ATG levels in blood and bone marrow, in these patients.
- Assess the binding capability of ATG to bone marrow resident myeloma cells.
- Determine if an ATG-resistant clone emerges after treatment.
OUTLINE: This is an open-label, pilot, dose-escalation study of anti-thymocyte globulin (ATG).
Patients receive ATG IV over 6-12 hours for 4, 6, or 8 days and oral sirolimus once daily on days 1-30 in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of ATG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.
Bone marrow aspirates and blood samples are collected at baseline and periodically during study treatment for drug sensitivity and pharmacokinetic studies.
After completion of study treatment, patients are followed every 3 weeks for up to 2 months and then monthly thereafter.
PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot, Phase-I Trial of Rabbit Anti-Thymocyte Globulin (rATG, Thymoglobulin™) in Combination With Rapamycin in Relapsed Multiple Myeloma (MM)|
|Study Start Date :||April 2006|
|Actual Primary Completion Date :||April 2011|
|Actual Study Completion Date :||April 2011|
- Biological: anti-thymocyte globulin
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
- Drug: sirolimus
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
- Dose-limiting toxicity and maximum tolerated dose [ Time Frame: Duration of the study ]
- Relapse rates as measured by standard response criteria [ Time Frame: Duration of the study ]
- Laboratory correlative studies [ Time Frame: During treatment ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00317798
|United States, New York|
|James P. Wilmot Cancer Center at University of Rochester Medical Center|
|Rochester, New York, United States, 14642|
|Principal Investigator:||J. J. Ifthikharuddin, MD||James P. Wilmot Cancer Center|
|Principal Investigator:||Martin S. Zand, MD, PhD||James P. Wilmot Cancer Center|