Suspended

Study of DT388GMCSF Fusion Protein in Acute Myelogenous Leukemia (AML) and Chronic Myelomonocytic Leukemia (CMML)

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What is being tested

DTGM

Drug
Who is being recruted

Acute Myelogenous Leukemia

+ Chronic Myelomonocytic Leukemia
Over 18 Years
+17 Eligibility Criteria

See all eligibility criteria

How is the trial designed

Treatment Study

Phase 1
Interventional
Study Start: December 2003

See protocol details

Summary

Principal SponsorM.D. Anderson Cancer Center
Last updated: February 22, 2012
Sourced from a government-validated database.Claim as a partner
Study start date: December 1, 2003Actual date on which the first participant was enrolled.

DTGM belongs to a new generation of drugs designed to target leukemic cells. To achieve this, DTGM takes advantage of the ability of naturally-produced growth factor (GM, granulocyte-macrophage stimulating factor) to deliver a drug (diphtheria toxin) to cells; preferably leukemic cells. It then attaches to the cells and allows the toxin to enter the leukemic cells and destroy them. The majority of malignant myeloid progenitor cells express receptors for GM-CSF. The fusion of GM-CSF with diphtheria toxin allows a targeting of cells with GM-CSF receptors for effects of the toxin while sparing GM-CSF receptor-lacking multipotent stem cells. The great majority of AML cells express GM-CSF receptors and DT388GMCSF has shown selective killing of AML and CMML progenitors in vitro while sparing normal progenitor cells. When administered as a single bolus to rodents, adequate blood DT388GMCSF biological activity was found to kill several logs of leukemic cells. A phase I clinical trial of DT388GMCSF given as a daily bolus i.v. infusion for up to 5 consecutive days was completed in 38 patients. The study defined liver toxicity as the DLT. The liver toxicity was observed only in patients > 50 years and receiving steroids. Responses were seen in four patients consisting of one complete remission and 3 partial remission of short duration. Peak drug levels were inversely proportional to pre-treatment DT388GMCSF antibody levels. Because of the observed significant preclinical activity in AML and CMML, clinical activity in chemorefractory patients with AML, the association of toxicities with steroid exposure, and association of the drug level with antibody titer that could be decreased with DT388GMCSF exposure, the current follow up phase I trial is designed based on a new administration and is a dose - finding trial also aimed to better determine and control side effects, improve drug pharmacokinetics and provide initial insight into antileukemic activity of this novel agent, delivered at a prolonged intermittent schedule.

Official TitleA Phase I Study of DT388GMCSF Fusion Protein in Acute Myelogenous Leukemia (AML) and Chronic Myelomonocytic Leukemia (CMML) 
Principal SponsorM.D. Anderson Cancer Center
Last updated: February 22, 2012
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
7 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Treatment Study
These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

How participants are assigned to different groups/arms
In this clinical study, all participants receive the same treatment. Since there is only one group, there is no need for randomization or assignment to different arms. This type of study is often used to test a new treatment without comparing it to another.

Other Ways to Assign Participants
Randomized allocation: Participants are assigned randomly, like flipping a coin, to ensure fairness and reduce bias.
Non-randomized allocation: Participants are assigned based on specific factors, such as their medical condition or a doctor's decision.

How treatments are given to participants
In this study, all participants receive the same treatment. This approach is often used to evaluate the effects of a single intervention without comparing it to another.

Other Ways to Assign Treatments
Parallel assignment: Participants are split into separate groups, each receiving a different treatment.
Cross-over assignment: Participants switch between treatments during the study.
Factorial assignment: Participants receive different combinations of treatments.
Sequential assignment: Participants receive treatments one after another in a specific order, possibly based on individual responses.
Other assignment: Treatment assignment does not follow a standard or predefined design.

How the effectiveness of the treatment is controlled
In a non placebo-controlled study, no participants receive an inert substance (placebo) to compare outcomes. Instead, all participants receive either the experimental treatment or an alternative treatment (often the Standard of Care). This method allows researchers to compare the effects of the experimental treatment with those of a different active intervention, rather than a placebo.

Other Options
Placebo-Controlled: A placebo is used to compare the effects of the experimental treatment with those of an inert substance, isolating the true treatment effect.

How the interventions assigned to participants is kept confidential
Everyone involved in the study knows which treatment is being given. This is typically used when it's not possible or necessary to hide the treatment details from participants or researchers.

Other Ways to Mask Information
Single-blind: Participants do not know which treatment they are receiving, but researchers do.
Double-blind: Neither participants nor researchers know which treatment is given.
Triple-blind: Participants, researchers, and outcome assessors do not know which treatment is given.
Quadruple-blind: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
Over 18 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Acute Myelogenous Leukemia
Chronic Myelomonocytic Leukemia
Criteria
9 inclusion criteria required to participate
Patients with refractory or relapsed AML ( marrow blasts > 20% ), must have failed induction therapy or have relapsed after CR duration < 6 months following induction therapy, untreated or refractory to salvage chemotherapy. Relapsed AML patients with CR duration \> 6 months or previously untreated patients refusing chemotherapy and not considered for treatments of higher priority are also eligible
Patients with chronic myelomonocytic leukemia (CMML) who failed at least one course of chemo- or biological therapy( including trial of erythropoietin), or patients with relapsed CMML. Previously untreated CMML patients with HB < or = 12 g / dL, not eligible for protocols of higher priority or not wishing to receive chemotherapy
Patients must have an ECOG performance status of < 2
Patients must have WBC count < 10,000/mL prior to initiating the treatment. The WBC count must be stabilized below this level for at least three days by leukopheresis or hydroxyurea. Hydroxyurea must be discontinued one day prior to initiation of DT388GMCSF treatment

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8 exclusion criteria prevent from participating
Patients with serious concurrent medical problems. Patients with proven bacterial infections are not eligible until the resolution of the infection (patient afebrile who completed antibacterial therapy, not on steroids). Patients with active fungal infections are eligible only if evidence of response to antifungal medications is documented and fever does not exceed 38C for at least 2 days
Inability to give informed consent because of psychiatric problems or other serious medical problems
Pregnant or nursing women
Patients with documented CNS leukemia or leukemia with CNS symptoms

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Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
One single intervention group 

is designated in this study

This study does not include a placebo group 

Treatment Groups
Group I
Experimental
Starting dose of DTGM fusion protein 2 mcg/kg/day as a short (30 min) intravenous infusion, three times /week (M,W,F) for two consecutive weeks. In absence of defined grade 3/4 nonhematological toxicities in the first 0/3 or 1/6 patients, the dose will be escalated by 1 mcg/kg/day for the next patient cohort.

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 1 location
Suspended
The University of Texas M.D. Anderson Cancer CenterHouston, United StatesSee the location
SuspendedOne Study Center