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A Pilot, Phase-I Trial of Rabbit Anti-Thymocyte Globulin (rATG, Thymoglobulin™) in Combination With Rapamycin in Relapsed Multiple Myeloma (MM)

Phase 1
18 Years
Not Enrolling
Drug/Agent Toxicity by Tissue/Organ, Multiple Myeloma and Plasma Cell Neoplasm

Thank you

Trial Information

A Pilot, Phase-I Trial of Rabbit Anti-Thymocyte Globulin (rATG, Thymoglobulin™) in Combination With Rapamycin in Relapsed Multiple Myeloma (MM)



- 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


- 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

- 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

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.

Inclusion Criteria


- 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

- 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


- Zubrod performance status 0-2

- 3-4 allowed if, in the opinion of the investigator, secondary to MM-related bone

- 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

- 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


- 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

- No other concurrent investigational agents

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Dose-limiting toxicity and maximum tolerated dose

Outcome Time Frame:

Duration of the study

Safety Issue:


Principal Investigator

J. J. Ifthikharuddin, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

James P. Wilmot Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

April 2006

Completion Date:

April 2011

Related Keywords:

  • Drug/Agent Toxicity by Tissue/Organ
  • Multiple Myeloma and Plasma Cell Neoplasm
  • drug/agent toxicity by tissue/organ
  • stage I multiple myeloma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • refractory multiple myeloma
  • Neoplasms
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma



James P. Wilmot Cancer Center at University of Rochester Medical CenterRochester, New York  14642