AMD3100 With Busulfan, Fludarabine and Thymoglobulin for Allogeneic Stem Cell Transplant for AML and MDS

NCT00396968 | Withdrawn Phase 1

• 1 other identifier: AMD3100-2201
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

AMD3100 given in combination with busulfan, fludarabine (and thymoglobulin (ATG) for unrelated or HLA nonidentical donors) preparative regimen in patients with acute myelogenous leukemia (AML) / myelodysplastic syndromes (MDS). This study aims to determine if in AML and MDS patients there is a reduction of malignant cells and enhanced elimination of the leukemia as assessed by progression free survival. Secondary goals will be to assess effects on engraftment, graft versus host disease (GVHD) and immune reconstitution.

Conditions

Acute Myelogenous Leukemia; Myelodysplastic Syndromes

Keywords

AMD3100; Acute Myelogenous Leukemai; Myelodysplastic Syndromes; Allogeneic stem cell transplantation

Outcome Measures

Primary Outcomes (3)

• To determine if AMD3100 given in a sequential dose escalation at 80, 160 and 240 µg/kg in combination with busulfan, fludarabine (and ATG for unrelated or HLA nonidentical donors) for treatment of AML/MDS:

• Stage 1 - Is Safe

• Stage 2 - Will improve progression free survival post allogeneic stem cell transplantation from an HLA compatible donor compared to historical controls.

Secondary Outcomes (3)

• Stage 2 - Determine the time from stem cell transplant to PMN engraftment compared to historical controls.

• Determine the rate and severity grading of GVHD compared to historical controls.

• Determine immune reconstitution compared to historical controls.

Interventions

AMD3100 DRUG

Allogeneic Stem Cell Transplantation PROCEDURE

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis of AML past first remission, (i.e., in first or subsequent relapse, in second or greater remission or primary induction failure) or MDS with intermediate or high risk International Prognostic Scoring System (IPSS) score (71) or having failed to respond or recurred after chemotherapy.
• WBC \<20 x 10e9/l.
• Patients should have a histocompatible, related or unrelated volunteer donor available for a PBSC transplant. A histocompatible donor is defined as HLA matched for at least 9 of 10 HLA A, B, C, DR and DQ antigens by high-resolution DNA technique per departmental routine.
• Patient has not been administered any other systemic chemotherapeutic drug (including Mylotarg) within 21 days prior to trial enrollment. (Hydroxyurea is permitted if indicated to control induction refractory disease, and intrathecal (IT) chemotherapy is allowed if indicated as maintenance treatment for previously diagnosed leptomeningeal disease (LMD), that has been in remission for at least 3 months prior to enrollment on this study).
• Zubrod performance status \< 2.
• Left ventricular ejection fraction \>45%. No uncontrolled arrhythmias or uncontrolled symptomatic cardiac disease. This should be performed within 28 days prior to study entry.
• No symptomatic pulmonary disease. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and diffusion capacity of carbon monoxide (DLCO) \> 50 % of expected, corrected for hemoglobin. This should be performed within 28 days prior to study entry.
• Serum creatinine \<1.5 mg/dl.
• Serum glutamic pyruvic transaminase (SGPT) \<200 IU/ml. Total serum bilirubin and alkaline phosphatase \<2.5 times laboratory standard upper limit of normal (ULN), or considered not clinically significant by the protocol PI.
• Patient or patient's legal representative able to sign informed consent.

You may not qualify if:

• HIV positive.
• Female patient who is pregnant (negative pregnancy test is required for all women of child-bearing-potential).
• Pleural/pericardial effusion or ascites estimated \> 1 liter.
• Uncontrolled infection. Patients considered to have uncontrolled infections including active fungal pneumonia are not eligible. Patients with infections or pulmonary infiltrates responding to antimicrobial treatment are eligible. Infectious Disease consultation should be obtained if indicated. These cases should be discussed with the Protocol PI who is the final arbiter of eligibility.
• Evidence of chronic active hepatitis or cirrhosis.
• Patients should not have received investigational agent(s) or intensive chemotherapy within 21 days of starting the study treatment regimen.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead
• AnorMED: collaborator

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

plerixafor

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: November 6, 2006
• First Posted: November 8, 2006
• Last Updated: February 11, 2014

Record last verified: 2014-02