Clinical trial NCT00089050: Gemtuzumab Ozogamicin and Cyclosporine in Treating Older Patients With Relapsed Acute Myeloid Leukemia
Official title: A Phase II Trial Combining Gemtuzumab Ozogamicin (Mylotarg) With Cyclosporine for the Treatment of Relapsed Acute Myeloid Leukemia in Adults Over Age 60
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Keywords: recurrent adult acute myeloid leukemia
adult acute minimally differentiated myeloid leukemia (M0)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myeloblastic leukemia with maturation (M2)
adult acute myelomonocytic leukemia (M4)
adult acute monoblastic leukemia (M5a)
adult acute monocytic leukemia (M5b)
adult erythroleukemia (M6a)
adult pure erythroid leukemia (M6b)
adult acute megakaryoblastic leukemia (M7)
adult acute basophilic leukemia
adult acute eosinophilic leukemia
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-08-05
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Monoclonal antibodies such as gemtuzumab ozogamicin can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Cyclosporine may increase the effectiveness of gemtuzumab ozogamicin by making cancer cells more sensitive to the drug. Combining gemtuzumab ozogamicin with cyclosporine may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving gemtuzumab ozogamicin together with cyclosporine works in treating older patients with relapsed acute myeloid leukemia.

Detailed description: OBJECTIVES:

Primary

* Determine the efficacy of gemtuzumab ozogamicin and cyclosporine, in terms of the complete remission rate, in older patients with relapsed acute myeloid leukemia.
* Determine the toxicity and pharmacokinetics of this regimen in these patients.

Secondary

* Correlate clinical response with laboratory studies of drug susceptibility in patients treated with this regimen.

OUTLINE: Patients receive cyclosporine IV continuously over 72 hours on days 1-3 and 15-17. Eight hours after initiation of each cyclosporine infusion, patients receive gemtuzumab ozogamicin IV over 2 hours on days 1 and 15. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 25-50 patients will be accrued for this study within 3 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Morphologically confirmed acute myeloid leukemia (AML) by bone marrow aspirate

  * More than 20% blasts by morphologic criteria
  * Relapsed disease ≥ 3 months after prior complete remission
* Blasts CD33-positive by flow cytometry
* No primary hematologic disorder that preceded initial presentation with AML
* No documented secondary AML related to prior chemotherapy or toxin exposure
* No acute promyelocytic leukemia (FAB M3)
* Not a candidate for transplant therapy
* No active CNS leukemia

PATIENT CHARACTERISTICS:

Age

* 60 and over

Performance status

* Karnofsky 70-100%

Life expectancy

* Not specified

Hematopoietic

* WBC ≤ 30,000/mm\^3 (hydroxyurea allowed)

Hepatic

* Bilirubin ≤ 1.5 times upper limit of normal (ULN)
* AST or ALT ≤ 1.5 times ULN

Renal

* Creatinine ≤ 1.5 mg/dL

Other

* HIV negative
* No uncontrolled infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not planning hematopoietic stem cell transplantation immediately after study therapy

Chemotherapy

* See Disease Characteristics
* See Hematopoietic

Endocrine therapy

* Not specified

Radiotherapy

* Not specified

Surgery

* Not specified

Other

* More than 1 month since prior investigational agents
* No other concurrent anticancer therapy
* No administration of any of the following for 24 hours after cyclosporine administration:

  * Diltiazem
  * Verapamil
  * Erythromycin
  * Clarithromycin
  * Metoclopramide
  * Phenytoin
  * Rifampin
  * Phenobarbital
  * Aminoglycosides
  * Amphotericin B
  * Vancomycin
  * Cimetidine
  * Ranitidine
  * Trimethoprim/sulfamethoxazole
  * Ketoconazole
  * Fluconazole
  * Itraconazole
  * Voriconazole
  * Carbamazepine

Primary outcomes:
measure: Efficacy in terms of complete remission rate
measure: Toxicity
measure: Pharmacokinetics
Secondary outcomes:
measure: Correlate clinical response to laboratory studies of drug susceptibility
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Fred Hutchinson Cancer Center
name: Stephen H. Petersdorf, MD
role: PRINCIPAL_INVESTIGATOR
References: