Leukemia, Myeloid, Acute
Conditions
Keywords
Plerixafor, CXCR4, Chemosensitization
Brief summary
This study is a phase I/II study to determine the safety and efficacy of AMD3100 when combined with mitoxantrone, etoposide, and cytarabine in patients with relapsed or refractory AML. We hypothesize that disrupting the interaction between AML blasts and the marrow microenvironment with AMD3100 may enhance the cytotoxic effect of chemotherapy.
Detailed description
The interaction of leukemic blasts with the bone marrow microenvironment is postulated to be an important mediator of chemoresistance in AML. Although a number of receptor / ligand pairs have been implicated, the CXCR4 / SDF-1 axis functions as the principal regulator of homing and retention of both normal and malignant hematopoietic cells in the marrow. AMD3100 is a bicyclam molecule which reversibly blocks CXCR4 binding to SDF-1 and is being developed clinically as a mobilization agent for hematopoietic stem cell transplantation. Preclinical data from our group has demonstrated that in murine models, plerixafor can disrupt the interaction of leukemic cells with the marrow microenvironment and sensitize blasts to the effect of chemotherapy. Based on these data, we have initiated a phase I/II study in patients with relapsed or refractory AML in which plerixafor is administered prior to salvage chemotherapy.
Interventions
Sponsors
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Acute myeloid leukemia diagnosed by WHO criteria with one of the following: 1. Primary refractory disease following \>= 1 rounds of induction chemotherapy 2. First relapse or higher 2. Age between 18 and 70 years of age 3. Adequate organ function defined as Creatinine \<= 1.5 x institutional ULN; AST, ALT, total bilirubin \<= 2 x ULN; Left ventricular ejection fraction of \>= 40% by MUGA scan 4. Women of childbearing potential and sexually active males must be willing and able to use effective contraception while on study 5. Able to provide signed informed consent prior to registration on study
Exclusion criteria
1. Acute promyelocytic leukemia (AML with t(15;17)(q22;q11) and variants) 2. Peripheral blood blast count \> 20 x 103 /mm3 3. Active CNS involvement with leukemia 4. Previous treatment with MEC or other regimen containing both mitoxantrone and etoposide 5. Pregnant or nursing 6. Receiving any other investigational agent 7. Colony stimulating factors filgrastim, pegfilgrastim or sargramostim within 2 weeks of study 8. Less than 2 weeks from the completion of any previous cytotoxic chemotherapy 9. Severe concurrent illness that would limit compliance with study requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase I Only: Optimal Dose of AMD3100 Plus MEC in Patients With Relapsed or Refractory AML | Completion of all patients in Phase I portion (232 days) | A standard 3+3 design was used in the Phase I portion starting with the AMD3100 dose of 80 mcg/kg and escalating by 80 mcg/kg for each successive cohort up to a maximum of 240 mcg/kg/d. The optimal dose was defined as the highest dose of AMD3100 \<= 240 mcg/kg at which 0-1 of 6 patients experienced a dose limiting toxicity. |
| Phase II Only: Complete Response Rate of AMD3100 + MEC | 42 days | Responses were assessed according to the International Working Group Criteria for AML. All patients who received at least one dose of AMD3100 were considered evaluable for response. Response rate was the rate of complete remission plus complete remission with incomplete blood count recovery (CR + CRi). |
| Ability of AMD3100 + MEC to Induce dsDNA Damage and Apoptosis in Leukemic Blasts From Bone Marrow or Peripheral Blood Fractions | 42 days | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I) | Day 0 | Measured at 0 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, and 24 hours after AMD3100 dose on Day 0. Characterization of the mobilized cells as well as the kinetics of mobilization will be determined by analyzing the surface expression of mobilized cells by flow cytometry at the specified time points in conjunction with their total leukocyte count from the patient's CBC. |
| Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I) | Day 0 | Measured at 0 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, and 24 hours after AMD3100 dose on Day 0. |
| Pharmacokinetics of AMD3100 on MEC | Day 1 - Phase 2 only | — |
| Safety and Tolerability of AMD3100 + MEC. | 42 days | Treatment related mortality (deaths occurring during treatment) |
| Treatment Failure | 42 days | Treatment failures includes those patients for whom treatment has failed to achieve a CR or a CRi. |
| Overall Survival | 1 year | — |
| Relapse-free Survival | 1 year | This is determined only for patients achieving a complete remission. Defined as the interval from the date of the first documentation of a leukemia free state to date of recurrence or death due to any cause. Kaplain-Meier estimate was used. |
| Time to Progression | Every 6 months | — |
| Time to Neutrophil Recovery | 42 days | Defined as the date of the first dose of AMD3100 to the date that the absolute neutrophil count \>1,000 cells/mm\^3. |
| Time to Platelet Recovery | 42 days | Defined as the date of the first dose of AMD3100 to the date that the platelet count is \>100,000/mm3 in the absence of platelet transfusions. |
Countries
United States
Participant flow
Recruitment details
Recruitment occurred from 07/12/2007 until 01/14/2010.
Participants by arm
| Arm | Count |
|---|---|
| Phase I Dose Escalation (Dose Level 1) * AMD3100 SQ on days 0-5
* Mitoxantrone on days 1-5
* Etoposide on days 1-5
* Cytarabine on days 1-5
Dose Level 1 AMD3100 dose = 80 mcg/kg/d | 3 |
| Phase I Dose Escalation (Dose Level 2) * AMD3100 SQ on days 0-5
* Mitoxantrone on days 1-5
* Etoposide on days 1-5
* Cytarabine on days 1-5
Dose Level 2 AMD3100 dose = 160 mcg/kg/d | 3 |
| Phase II Dose Treatment (Dose Level 3) * AMD 3100 SQ on days 0-5
* Mitoxantrone on days 1-5
* Etoposide on days 1-5
* Cytarabine on days 1-5
Dose Level 3 AMD3100 dose=240 mcg/kg/d (this was the Phase II dose).
The 6 participants that were enrolled in Dose Level 3 in the Phase I portion of the study were carried over to the Phase II analysis. 40 additional patients were enrolled in the Phase II portion of the study using the Dose Level 3 dose. | 46 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Phase I Dose Escalation (Dose Level 1) | Phase I Dose Escalation (Dose Level 2) | Phase II Dose Treatment (Dose Level 3) | Total |
|---|---|---|---|---|
| Acute myeloid leukemia (AML) source De novo AML | 3 participants | 2 participants | 36 participants | 41 participants |
| Acute myeloid leukemia (AML) source Prior MDS/MPD | 0 participants | 0 participants | 6 participants | 6 participants |
| Acute myeloid leukemia (AML) source Therapy related | 0 participants | 1 participants | 4 participants | 5 participants |
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 5 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 3 Participants | 40 Participants | 46 Participants |
| Age, Continuous | 58 years | 24 years | 51 years | 51 years |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 | 2 participants | 2 participants | 25 participants | 29 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 | 1 participants | 1 participants | 10 participants | 12 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 2 | 0 participants | 0 participants | 3 participants | 3 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Unknown | 0 participants | 0 participants | 8 participants | 8 participants |
| Gender Female | 2 Participants | 2 Participants | 26 Participants | 30 Participants |
| Gender Male | 1 Participants | 1 Participants | 20 Participants | 22 Participants |
| Prior transplantation Allogeneic | 0 participants | 0 participants | 6 participants | 6 participants |
| Prior transplantation Autologous | 0 participants | 0 participants | 3 participants | 3 participants |
| Prior transplantation No prior transplant | 3 participants | 3 participants | 37 participants | 43 participants |
| Region of Enrollment United States | 3 participants | 3 participants | 46 participants | 52 participants |
| Treatment Indication First relapse, first salvage | 3 participants | 2 participants | 32 participants | 37 participants |
| Treatment Indication Primary refractory | 0 participants | 1 participants | 10 participants | 11 participants |
| Treatment Indication >=Second relapse/salvage | 0 participants | 0 participants | 4 participants | 4 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 46 / 46 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 3 / 46 |
Outcome results
Primary
Ability of AMD3100 + MEC to Induce dsDNA Damage and Apoptosis in Leukemic Blasts From Bone Marrow or Peripheral Blood Fractions
Time frame: 42 days
Population: This outcome was not analyzed as data was not collected.
Primary
Phase II Only: Complete Response Rate of AMD3100 + MEC
Responses were assessed according to the International Working Group Criteria for AML. All patients who received at least one dose of AMD3100 were considered evaluable for response. Response rate was the rate of complete remission plus complete remission with incomplete blood count recovery (CR + CRi).
Time frame: 42 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase I Dose Escalation | Phase II Only: Complete Response Rate of AMD3100 + MEC | CR + CRi | 56 percentage of participants |
| Phase I Dose Escalation | Phase II Only: Complete Response Rate of AMD3100 + MEC | CR only | 47 percentage of participants |
| Primary Refractory | Phase II Only: Complete Response Rate of AMD3100 + MEC | CR only | 20 percentage of participants |
| Primary Refractory | Phase II Only: Complete Response Rate of AMD3100 + MEC | CR + CRi | 20 percentage of participants |
| >= Second Relapse/Salvage | Phase II Only: Complete Response Rate of AMD3100 + MEC | CR + CRi | 25 percentage of participants |
| >= Second Relapse/Salvage | Phase II Only: Complete Response Rate of AMD3100 + MEC | CR only | 25 percentage of participants |
| Total | Phase II Only: Complete Response Rate of AMD3100 + MEC | CR + CRi | 46 percentage of participants |
| Total | Phase II Only: Complete Response Rate of AMD3100 + MEC | CR only | 39 percentage of participants |
Primary
Phase I Only: Optimal Dose of AMD3100 Plus MEC in Patients With Relapsed or Refractory AML
A standard 3+3 design was used in the Phase I portion starting with the AMD3100 dose of 80 mcg/kg and escalating by 80 mcg/kg for each successive cohort up to a maximum of 240 mcg/kg/d. The optimal dose was defined as the highest dose of AMD3100 \<= 240 mcg/kg at which 0-1 of 6 patients experienced a dose limiting toxicity.
Time frame: Completion of all patients in Phase I portion (232 days)
Population: The Phase I Dose Escalation portion included (3) patients enrolled in Dose Level 1 and (3) patients enrolled in Dose Level 2. The (6) patients enrolled in Dose Level 3 that determined the Phase II dose are included in the population for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase I Dose Escalation | Phase I Only: Optimal Dose of AMD3100 Plus MEC in Patients With Relapsed or Refractory AML | 240 mcg/kg |
Secondary
Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I)
Measured at 0 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, and 24 hours after AMD3100 dose on Day 0.
Time frame: Day 0
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase I Dose Escalation | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I) | AML blasts at 1 hour | 26.0 percentage of AML blasts |
| Phase I Dose Escalation | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I) | AML blasts at 12 hours | 27.0 percentage of AML blasts |
| Phase I Dose Escalation | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I) | AML blasts at 4 hours | 37.0 percentage of AML blasts |
| Phase I Dose Escalation | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I) | AML blasts at 2 hours | 26.0 percentage of AML blasts |
| Phase I Dose Escalation | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I) | AML blasts at 8 hours | 32.0 percentage of AML blasts |
| Phase I Dose Escalation | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I) | AML blasts at 0 hours | 46.0 percentage of AML blasts |
| Phase I Dose Escalation | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I) | AML blasts at 24 hours | 35.0 percentage of AML blasts |
| Phase I Dose Escalation | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I) | AML blasts at 6 hours | 31.0 percentage of AML blasts |
| Primary Refractory | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I) | AML blasts at 2 hours | 37.5 percentage of AML blasts |
| Primary Refractory | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I) | AML blasts at 24 hours | 23 percentage of AML blasts |
| Primary Refractory | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I) | AML blasts at 0 hours | 4.0 percentage of AML blasts |
| Primary Refractory | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I) | AML blasts at 1 hour | 9.0 percentage of AML blasts |
| Primary Refractory | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I) | AML blasts at 12 hours | 45.0 percentage of AML blasts |
| Primary Refractory | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I) | AML blasts at 4 hours | 16.0 percentage of AML blasts |
| Primary Refractory | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I) | AML blasts at 6 hours | 14.0 percentage of AML blasts |
| Primary Refractory | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I) | AML blasts at 8 hours | 19.0 percentage of AML blasts |
| >= Second Relapse/Salvage | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I) | AML blasts at 4 hours | 30.0 percentage of AML blasts |
| >= Second Relapse/Salvage | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I) | AML blasts at 0 hours | 43.5 percentage of AML blasts |
| >= Second Relapse/Salvage | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I) | AML blasts at 8 hours | 26.0 percentage of AML blasts |
| >= Second Relapse/Salvage | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I) | AML blasts at 6 hours | 27.0 percentage of AML blasts |
| >= Second Relapse/Salvage | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I) | AML blasts at 24 hours | 55 percentage of AML blasts |
| >= Second Relapse/Salvage | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I) | AML blasts at 2 hours | 32.5 percentage of AML blasts |
| >= Second Relapse/Salvage | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I) | AML blasts at 1 hour | 30.5 percentage of AML blasts |
| >= Second Relapse/Salvage | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I) | AML blasts at 12 hours | 35.0 percentage of AML blasts |
Secondary
Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I)
Measured at 0 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, and 24 hours after AMD3100 dose on Day 0. Characterization of the mobilized cells as well as the kinetics of mobilization will be determined by analyzing the surface expression of mobilized cells by flow cytometry at the specified time points in conjunction with their total leukocyte count from the patient's CBC.
Time frame: Day 0
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase I Dose Escalation | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I) | Total leukocytes at 0 hours | 2.5 cells x 10^3/microliter |
| Phase I Dose Escalation | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I) | Total leukocytes at 1 hour | 4.3 cells x 10^3/microliter |
| Phase I Dose Escalation | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I) | Total leukocytes at 2 hours | 4 cells x 10^3/microliter |
| Phase I Dose Escalation | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I) | Total leukocytes at 4 hours | 4.7 cells x 10^3/microliter |
| Phase I Dose Escalation | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I) | Total leukocytes at 6 hours | 4.8 cells x 10^3/microliter |
| Phase I Dose Escalation | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I) | Total leukocytes at 8 hours | 4.5 cells x 10^3/microliter |
| Phase I Dose Escalation | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I) | Total leukocytes at 12 hours | 5.1 cells x 10^3/microliter |
| Phase I Dose Escalation | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I) | Total leukocytes at 24 hours | 4.3 cells x 10^3/microliter |
| Primary Refractory | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I) | Total leukocytes at 2 hours | 8.5 cells x 10^3/microliter |
| Primary Refractory | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I) | Total leukocytes at 12 hours | 12.1 cells x 10^3/microliter |
| Primary Refractory | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I) | Total leukocytes at 4 hours | 9.4 cells x 10^3/microliter |
| Primary Refractory | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I) | Total leukocytes at 6 hours | 11.3 cells x 10^3/microliter |
| Primary Refractory | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I) | Total leukocytes at 8 hours | 12.0 cells x 10^3/microliter |
| Primary Refractory | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I) | Total leukocytes at 0 hours | 4.7 cells x 10^3/microliter |
| Primary Refractory | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I) | Total leukocytes at 1 hour | 7.0 cells x 10^3/microliter |
| Primary Refractory | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I) | Total leukocytes at 24 hours | 7.9 cells x 10^3/microliter |
| >= Second Relapse/Salvage | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I) | Total leukocytes at 2 hours | 7.5 cells x 10^3/microliter |
| >= Second Relapse/Salvage | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I) | Total leukocytes at 1 hour | 6.4 cells x 10^3/microliter |
| >= Second Relapse/Salvage | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I) | Total leukocytes at 0 hours | 3.5 cells x 10^3/microliter |
| >= Second Relapse/Salvage | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I) | Total leukocytes at 4 hours | 8.3 cells x 10^3/microliter |
| >= Second Relapse/Salvage | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I) | Total leukocytes at 12 hours | 7.8 cells x 10^3/microliter |
| >= Second Relapse/Salvage | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I) | Total leukocytes at 8 hours | 8.9 cells x 10^3/microliter |
| >= Second Relapse/Salvage | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I) | Total leukocytes at 6 hours | 9.5 cells x 10^3/microliter |
| >= Second Relapse/Salvage | Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I) | Total leukocytes at 24 hours | 5.8 cells x 10^3/microliter |
Secondary
Overall Survival
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase I Dose Escalation | Overall Survival | 37 percentage of participants |
Secondary
Pharmacokinetics of AMD3100 on MEC
Time frame: Day 1 - Phase 2 only
Population: This was not performed.
Secondary
Relapse-free Survival
This is determined only for patients achieving a complete remission. Defined as the interval from the date of the first documentation of a leukemia free state to date of recurrence or death due to any cause. Kaplain-Meier estimate was used.
Time frame: 1 year
Population: This excludes the 25 participants who had treatment failure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase I Dose Escalation | Relapse-free Survival | 42.9 percentage of participants |
Secondary
Safety and Tolerability of AMD3100 + MEC.
Treatment related mortality (deaths occurring during treatment)
Time frame: 42 days
Population: The 46 patients include the 6 patients treated on Dose Level 3 of the Phase I portion of the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase I Dose Escalation | Safety and Tolerability of AMD3100 + MEC. | Sepsis | 2 participants |
| Phase I Dose Escalation | Safety and Tolerability of AMD3100 + MEC. | Adverse transfusion reaction w/febrile neutropenia | 1 participants |
Secondary
Time to Neutrophil Recovery
Defined as the date of the first dose of AMD3100 to the date that the absolute neutrophil count \>1,000 cells/mm\^3.
Time frame: 42 days
Population: This analysis includes patients who achieved a CR or a CRi.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I Dose Escalation | Time to Neutrophil Recovery | 28 days |
Secondary
Time to Platelet Recovery
Defined as the date of the first dose of AMD3100 to the date that the platelet count is \>100,000/mm3 in the absence of platelet transfusions.
Time frame: 42 days
Population: This analysis includes patients who achieved a CR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I Dose Escalation | Time to Platelet Recovery | 28.5 days |
Secondary
Time to Progression
Time frame: Every 6 months
Population: This outcome was not analyzed instead reason for treatment failure was analyzed as it provided better information on why the treatment did not work.
Secondary
Treatment Failure
Treatment failures includes those patients for whom treatment has failed to achieve a CR or a CRi.
Time frame: 42 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase I Dose Escalation | Treatment Failure | Persistent leukemia | 12 participants |
| Phase I Dose Escalation | Treatment Failure | Unknown | 1 participants |
| Phase I Dose Escalation | Treatment Failure | Death during aplasia | 1 participants |
| Primary Refractory | Treatment Failure | Persistent leukemia | 6 participants |
| Primary Refractory | Treatment Failure | Unknown | 0 participants |
| Primary Refractory | Treatment Failure | Death during aplasia | 2 participants |
| >= Second Relapse/Salvage | Treatment Failure | Death during aplasia | 0 participants |
| >= Second Relapse/Salvage | Treatment Failure | Persistent leukemia | 3 participants |
| >= Second Relapse/Salvage | Treatment Failure | Unknown | 0 participants |
| Total | Treatment Failure | Persistent leukemia | 21 participants |
| Total | Treatment Failure | Unknown | 1 participants |
| Total | Treatment Failure | Death during aplasia | 3 participants |