Phase I Evaluation of the Anti-CD-33 Immunotoxin Hum-195/rGel in Patients With Advanced Myeloid Malignancies


Phase 1
18 Years
N/A
Not Enrolling
Both
Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, Myeloproliferative Disorders, Anemia, Refractory, With Excess of Blasts

Thank you

Trial Information

Phase I Evaluation of the Anti-CD-33 Immunotoxin Hum-195/rGel in Patients With Advanced Myeloid Malignancies


Before therapy, all patients will be asked about their medical history, and a physical exam
(with measurement of vital signs) will be performed. A chest X-ray and an electrocardiogram
(ECG - a test to measure the electrical activity of the heart) will be performed. Blood
(about 4 teaspoons) will be drawn for routine tests and blood clotting tests. Women who are
able to become pregnant will have a urine pregnancy test done. A test will be done to
measure the amount of oxygen in your blood by placing a monitoring device on your finger.
Blood (about 1 teaspoon) will be taken to measure the amount of a protein that is present on
the diseased cells. During the study period, the study staff will draw blood samples for
routine tests, pharmacokinetic (PK) tests, and anti-drug antibody tests. Blood (about 1
teaspoon) will be drawn to measure the amount of a protein that is present on the diseased
cells. A bone marrow sample will also be obtained before treatment and on Study Day 28.

Patients will receive four injections of the immunotoxin. The immunotoxin is designed to
selectively destroy myeloid leukemia cells. The injections will be given through a vein
twice weekly for two weeks. Patients will then be evaluated twice weekly for the next two
weeks. If there has been improvement in the leukemia, or if the leukemia has remained
stable and there have been no serious side effects of treatment, patients will then receive
a second course of immunotoxin injections. These will again be given twice weekly for two
weeks. Depending on the effectiveness against leukemia and the side effects, patients may
receive maintenance treatment. This would also consist of two weekly injections given for
two weeks followed by two weeks of observation. Maintenance therapy may continue for up to
four months for partial response and up to two months for complete response.

This is an investigational study. Up to 36 patients will take part in this study.


Inclusion Criteria:



1. Patients with relapsed or refractory acute myelogenous leukemia (AML), Refractory
anemia with excess blasts in transformation (RAEB-t), Refractory Anemia with Excess
Blasts (RAEB), or chronic myelomonocytic leukaemia (CMML) who failed at least one
previous chemotherapy course. Patients with accelerated CML Ph+ or myeloid blastic
crisis are eligible. Patients in accelerated phase of non-Philadelphia chromosome +
myeloproliferative disorders are also eligible:

- P. vera,

- myelofibrosis

- essential thrombocytopenia with >5% blasts in the blood or bone marrow.

2. Male or female 18 yrs of age or older who have provided written informed consent

3. Tumor cells must be = or > 80% CD33 positive by flow cytometry

4. For women of childbearing potential (i.e. exclude post-menopausal women, women who
have been surgically sterilized), adequate birth control methods must be used.
Acceptable birth control methods are limited to oral contraceptives, implants,
diaphragm, IUD or spermicide used with a condom

5. White blood count (WBC) count <10,000/ml for AML, MDS, and myeloproliferative
disorders and up to 30,000 for accelerated CML

6. No cytotoxic chemotherapy for the two weeks prior to entering the study

7. No evidence of residual toxic effects grade 2 or higher from prior chemotherapy

8. Patients with proven bacterial infection are not eligible until resolution of the
infection (patient afebrile, not on steroids). Patients with active fungal infections
are eligible only if evidence of response to antifungal medications is documented and
they do not have fever exceeding 38°C

9. Creatinine - Patients should have values = or < 1.5 times the upper limit of
laboratory normal values

10. Liver function - Patients should have serum bilirubin values = or < 2.0 times the
upper limit of laboratory normal values. Patients should have SGOT and/or SGPT levels
= or < 2.5 times the upper limit of laboratory normal values

11. Cardiac function - Patients with cardiovascular disease should be < New York Heart
Association (NYHA) classification III

12. Pulmonary function - O2 saturation should be = or > 92% without exogenous O2
administered.

13. Neurologic function - Patients should have normal central nervous system function as
well as normal motor function consistent with = or < Grade 1 toxicity. Patients
should have peripheral sensory function damage (neuropathy) not exceeding Grade 1
toxicity

Exclusion Criteria:

Women who are pregnant or lactating

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD)

Outcome Description:

Dose-limiting toxicity considered to have occurred when (1) >grade 2 extramedullary toxicity possibly related to HuM195/rGel (except nausea, vomiting or diarrhea unless uncontrolled by optimal management, or electrolyte abnormalities unless clinically significant or not correctable after optimal replacement) is observed or (2) >42 days from day 1 of therapy elapse before return of neutrophil count to >500 and platelet count to >25,000 in absence of leukemia (i.e., with a normal or hypercellular bone marrow with <5% blasts).

Outcome Time Frame:

Continuous assessment of safety throughout entire study period and determination of dose-limiting toxicities at end of two week evaluation period (4 weeks from start of therapy).

Safety Issue:

Yes

Principal Investigator

Jorge Cortes, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

DM98-342

NCT ID:

NCT00038051

Start Date:

May 1999

Completion Date:

February 2013

Related Keywords:

  • Acute Myeloid Leukemia
  • Chronic Myelomonocytic Leukemia
  • Myeloproliferative Disorders
  • Anemia, Refractory, With Excess of Blasts
  • Acute Myeloid Leukemia
  • AML
  • Chronic Myelomonocytic Leukemia
  • CMML
  • Myeloproliferative Disorders
  • Refractory Anemia with Excess of Blasts
  • RAEB-t
  • RAEB
  • Hum-195/rGel
  • Anemia
  • Anemia, Refractory
  • Anemia, Refractory, with Excess of Blasts
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelomonocytic, Chronic
  • Leukemia, Myelomonocytic, Acute
  • Myeloproliferative Disorders

Name

Location
UT MD Anderson Cancer Center Houston, Texas  77030