Homoharringtonine With Oral Gleevec in Chronic, Accelerated and Blast Phase Chronic Myeloid Leukemia (CML)

• Sponsor: ChemGenex Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00114959
• Collaborator: (none)
• Enrollment: 15
• Location: 1
• Arm: 1
• Duration (Months): 41
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This will be an open label, multi-center study of up to 77 patients with CML in chronic, accelerated or blast phase who have developed resistance to or have failed previous treatment with Gleevec (imatinib mesylate). Because these patients may still be sensitive to Gleevec, adding Homoharringtonine may restore a response to Gleevec or the combined treatment may promote a better response than using Gleevec alone.

Condition or Disease	Intervention/Treatment	Phase
Myeloid Leukemia, Chronic; Myeloid Leukemia, Chronic, Accelerated-Phase; Blast Phase; Myeloid Leukemia, Chronic, Chronic-Phase	Drug: Homoharringtonine; Drug: Imatinib Mesylate	Phase 2

Detailed Description

Every 4 weeks, the study medicine Homoharringtonine will be given by vein daily for 5 days along with continuing daily doses of the approved medicine Gleevec taken by mouth. The safety and effectiveness of this combined treatment in CML patients will be studied. Patients who do not achieve a meaningful hematologic or cytogenetic response after 4 cycles or less will be discontinued. Otherwise, patients may continue additional cycles of this combined treatment for a maximum of 12 cycles.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Open-Label Study of the Intravenous Administration of Homoharringtonine (CGX-635) Combined With the Oral Administration of Gleevec in the Treatment of Patients With Chronic Myeloid Leukemia (CML) in Chronic, Accelerated, and Blast Phase
• Study Start Date: Oct 1, 2005
• Actual Primary Completion Date: Jun 1, 2008
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Homoharringtonine + Imatinib Mesylate Participants are administered homoharringtonine (omacetaxine) 2.5 mg/m^2 by continuous 24-hour intravenous infusion daily on Days 1-5 of each 4 week treatment cycle, and imatinib mesylate (Gleevec) by mouth with a daily dose of 400 mg for participants in the chronic phase of chronic myeloid leukemia (CML) or 600 mg for participants in the accelerated or blast phase of CML.

Drug: Homoharringtonine; Participants are administered homoharringtonine (omacetaxine) 2.5 mg/m^2 by continuous 24-hour intravenous (IV) infusion daily on Days 1-5 of each 4 week treatment cycle. Participants who do not achieve a meaningful hematologic or cytogenetic response by the end of the fourth cycle are discontinued from the study. Otherwise, participants may continue additional cycles of this combined treatment for a maximum of 12 cycles. Participants who achieved a molecular or cytogenetic response, or a complete hematologic remission (CHR), could undergo subsequent cycles with a maintenance schedule of homoharringtonine 2.5 mg/m^2 by continuous 24-hour IV infusion daily for 2 days every 4 weeks. Dose escalations in subsequent cycles were allowed by one day at a time if the participant was unable to maintain CHR in the maintenance schedule.; Other Names: Omacetaxine mepesuccinate CGX-635 ; Drug: Imatinib Mesylate; Taken by mouth with a daily dose of 400 mg for participants in the chronic phase of chronic myeloid leukemia (CML) or 600 mg for participants in the accelerated or blast phase of CML. For the first cycle of therapy only, imatinib was started on Day 4 of homoharringtonine treatment.; Other Names: Gleevac

Outcome Measures

Primary Outcome Measures

1. Proportion of Participants With Accelerated Phase or Blast Phase Chronic Myeloid Leukemia (CML) Who Achieve a Meaningful Response [up to month 4]

   Participants in accelerated or blast phase who converted to at least CML-chronic phase. CML in accelerated phase meets one or more of the following criteria: >=15% - <30% blasts in peripheral blood or bone marrow, >=30% blasts + promyelocytes in peripheral blood or bone marrow, >=20% basophils in peripheral blood; platelet count <100*10^9/L unrelated to therapy or clonal evolution. CML in blast phase have >=30% blasts in the bone marrow or presence of extramedullary disease. Meaningful responses include (in descending order of health) Complete Hematologic Remission (CHR) Partial Hematologic Remission (PHR) Hematologic Improvement (HI) Partial Response (PR) Return to Chronic Phase (RCP). A return to chronic phase involves the disappearance of blastic phase features and a return to chronic phase CML picture, i.e., peripheral blasts <15%, peripheral blasts and promyelocytes <30%, peripheral basophils <20%, and platelets >100*10^9/L.

2. Proportion of Participants With Chronic Phase Chronic Myeloid Leukemia (CML) Who Achieve a Meaningful Response [up to month 4]

   Participants who are not in complete hematologic remission (CHR) at study start must achieve at least a CHR, and participants who are in CHR at onset must demonstrate an improvement in their cytogenetics. A Complete Hematologic Remission (CHR) involves normalization of the bone marrow (less than 5% blasts) and peripheral blood with white blood cells < 10*10^9/L, absolute neutrophil count >=1*10^9/L, platelets >=100*10^9/L and no peripheral blasts, promyelocytes or myelocytes. This is in addition to disappearance of all signs and symptoms of the disease.

3. Number of Participants With Adverse Experiences (AEs) [up to 3 years]

   Summary of participants who had adverse events (AEs), who discontinued treatment due to the AE, who had serious adverse events (SAEs), and who had SAEs that were related to treatments. A serious adverse event is one that at any dose of the study drug or at any time during the period of observation: Results in death; Is life threatening; Requires inpatient hospitalization or prolongation of existing hospitalization; Results in persistent or significant disability/incapacity; Is a congenital anomaly/birth defect; Is medically important. The Investigator assessed each AE for potential causal relationship between the event and study drug. An investigator assessment of possibly, probably or unknown relation is considered related.

Secondary Outcome Measures

1. Participants With Complete Hematologic Remission Suppression of the Philadelphia Chromosome [up to month 4]

   Complete hematologic remission was further classified according to the suppression of the Philadelphia chromosome (Ph) as: No cytogenetic response - Ph positive 100% Minimal cytogenetic response - Ph positive 35-90% Partial cytogenetic response - Ph positive 1-34% Complete cytogenetic response - Ph positive 0%

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female patients 16 years or older

• Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) in either chronic, accelerated or blast phase

• Patients with chronic phase CML will be either refractory (failed to achieve hematologic or cytogenetic response) or resistant (responded initially but subsequently lost hematologic or cytogenetic response) to prior imatinib mesylate therapy. Failure to achieve cytogenetic response is defined as follows: no cytogenetic response after 3 months of therapy with imatinib mesylate, no major cytogenetic response at 12 months of therapy, loss of complete cytogenetic response documented twice, or loss of major cytogenetic response at least once.

• Patients with accelerated or blast phase may be newly diagnosed and previously untreated or if previously treated with imatinib mesylate, will be refractory or resistant to this agent or have failed to achieve at least a complete hematologic or cytogenetic response to treatment, as previously defined.

• Patients in accelerated phase will meet one or more of the following criteria: greater than or equal to 15% through less than 30% blasts in peripheral blood or bone marrow, greater than or equal to 30% blasts + promyelocytes in peripheral blood or bone marrow, greater than or equal to 20% basophils in peripheral blood, platelet count less than 100*10^9/L unrelated to therapy or clonal evolution.

• CML in blast phase will be defined as greater than or equal to 30% blasts in the bone marrow or presence of extramedullary disease

• Patients must have completed all previous anti-leukemic therapy for at least 2 weeks, except as noted, and have fully recovered from side effects of a previous therapy, unless disease progression necessitates early therapy. Patients may receive leukapheresis, hydroxyurea and anagrelide for up to 24 hours prior to start of study treatment. Patients receiving imatinib mesylate may continue to receive it uninterrupted, except for a 3-day window at treatment cycle 1.

• Bilirubin less than or equal to 2 times the upper limit of normal (ULN); alanine aminotransferase (ALT) less than or equal to 3 times ULN; creatinine less than or equal to 1.5 times ULN

• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2

• Be able to comply with the requirements of the entire study

• Be able and willing to provide written informed consent prior to any study related procedure

• Patients and their partners must use an effective contraceptive during the study dosing period. The following are considered effective contraceptives: oral contraceptive pill, condom, diaphragm plus spermicide, abstinence, patient or partner surgically sterile, patient or partner more than 2 years post-menopausal, or injectable or implantable agent/device.

Exclusion Criteria:

• New York Heart Association (NYHA) Class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia and requiring therapy, uncontrolled hypertension or congestive heart failure

• Myocardial infarction in the previous 12 weeks

• Other intercurrent illness which would preclude study conduct and assessment, including but not limited to another active malignancy, uncontrolled and active infection, positive human immunodeficiency virus (HIV) or human T-cell lymphotropic virus (HTLV) I/II status

• Pregnant or lactating

• Any medical or psychiatric condition which may compromise the ability to give written informed consent or to comply with the study protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Univ. of Texas M.D. Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• ChemGenex Pharmaceuticals

Investigators

• Study Director: Adam R Craig, M.D., PhD, ChemGenex Pharmaceuticals
• Principal Investigator: Jorge Cortes, M.D., Univ. of TX M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: ChemGenex Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00114959
• Other Study ID Numbers: CGX-635-CML-201; MDACC protocol #2005-0067
• First Posted: Jun 21, 2005
• Last Update Posted: Jan 15, 2015
• Last Verified: Jan 1, 2015

• Keywords provided by ChemGenex Pharmaceuticals: ChemGenex Pharmaceuticals, Ltd; ChemGenex Pharmaceuticals; ChemGenex; Chronic Myeloid Leukemia; Myeloid Leukemia, Chronic; Leukemia; Myeloid Leukemia; Chronic Phase; Accelerated Phase; Blast Phase; Myeloid, Leukemia, Chronic, Accelerated Phase; Myeloid, Leukemia, Chronic; Leukemia, Myeloid, Chronic; Leukemia, Myeloid, Chronic-Phase; Leukemia, Myeloid, Chronic Phase; Leukemia, Myeloid, Accelerated-Phase; Myeloid, Leukemia, Chronic, Chronic Phase; Leukemia, Myeloid, Accelerated Phase; Homoharringtonine; Omacetaxine
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Blast Crisis; Leukemia, Myeloid, Chronic-Phase; Leukemia, Myeloid, Accelerated Phase; Chronic Disease; Imatinib Mesylate; Homoharringtonine

Study Results

Participant Flow

Arm/Group Title	Homoharringtonine + Imatinib Mesylate
Arm/Group Description	Participants are administered homoharringtonine (omacetaxine) 2.5 mg/m^2 by continuous 24-hour intravenous infusion daily on Days 1-5 of each 4 week treatment cycle, and imatinib mesylate (Gleevec) by mouth with a daily dose of 400 mg for participants in the chronic phase of chronic myeloid leukemia (CML) or 600 mg for participants in the accelerated or blast phase of CML.
Period Title: Overall Study
STARTED	15
COMPLETED	7
NOT COMPLETED	8

Baseline Characteristics

Arm/Group Title	Homoharringtonine + Imatinib Mesylate
Arm/Group Description	Participants are administered homoharringtonine (omacetaxine) 2.5 mg/m^2 by continuous 24-hour intravenous infusion daily on Days 1-5 of each 4 week treatment cycle, and imatinib mesylate (Gleevec) by mouth with a daily dose of 400 mg for participants in the chronic phase of chronic myeloid leukemia (CML) or 600 mg for participants in the accelerated or blast phase of CML.
Overall Participants	15
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	55
Sex: Female, Male (Count of Participants)
Female	7 46.7%
Male	8 53.3%
Race/Ethnicity, Customized (participants) [Number]
Black	4 26.7%
Caucasian	10 66.7%
Hispanic	1 6.7%

Outcome Measures

1. Primary Outcome

Title	Proportion of Participants With Accelerated Phase or Blast Phase Chronic Myeloid Leukemia (CML) Who Achieve a Meaningful Response
Description	Participants in accelerated or blast phase who converted to at least CML-chronic phase. CML in accelerated phase meets one or more of the following criteria: >=15% - <30% blasts in peripheral blood or bone marrow, >=30% blasts + promyelocytes in peripheral blood or bone marrow, >=20% basophils in peripheral blood; platelet count <100*10^9/L unrelated to therapy or clonal evolution. CML in blast phase have >=30% blasts in the bone marrow or presence of extramedullary disease. Meaningful responses include (in descending order of health) Complete Hematologic Remission (CHR) Partial Hematologic Remission (PHR) Hematologic Improvement (HI) Partial Response (PR) Return to Chronic Phase (RCP). A return to chronic phase involves the disappearance of blastic phase features and a return to chronic phase CML picture, i.e., peripheral blasts <15%, peripheral blasts and promyelocytes <30%, peripheral basophils <20%, and platelets >100*10^9/L.
Time Frame	up to month 4

Outcome Measure Data

Analysis Population Description

No participants were analyzed since the study was intended to follow a Simon two stage design to test 18 participants in each stratum (chronic, accelerated and blast phases) for efficacy. Enrollment was insufficient.

Arm/Group Title	Homoharringtonine + Imatinib Mesylate
Arm/Group Description	Participants are administered homoharringtonine (omacetaxine) 2.5 mg/m^2 by continuous 24-hour intravenous infusion daily on Days 1-5 of each 4 week treatment cycle, and imatinib mesylate (Gleevec) by mouth with a daily dose of 400 mg for participants in the chronic phase of chronic myeloid leukemia (CML) or 600 mg for participants in the accelerated or blast phase of CML.
Measure Participants	0

2. Primary Outcome

Title	Proportion of Participants With Chronic Phase Chronic Myeloid Leukemia (CML) Who Achieve a Meaningful Response
Description	Participants who are not in complete hematologic remission (CHR) at study start must achieve at least a CHR, and participants who are in CHR at onset must demonstrate an improvement in their cytogenetics. A Complete Hematologic Remission (CHR) involves normalization of the bone marrow (less than 5% blasts) and peripheral blood with white blood cells < 10*10^9/L, absolute neutrophil count >=1*10^9/L, platelets >=100*10^9/L and no peripheral blasts, promyelocytes or myelocytes. This is in addition to disappearance of all signs and symptoms of the disease.
Time Frame	up to month 4

Outcome Measure Data

Analysis Population Description

No participants were analyzed since the study was intended to follow a Simon two stage design to test 18 participants in each stratum (chronic, accelerated and blast phases) for efficacy. Enrollment was insufficient.

Arm/Group Title	Homoharringtonine + Imatinib Mesylate
Arm/Group Description	Participants are administered homoharringtonine (omacetaxine) 2.5 mg/m^2 by continuous 24-hour intravenous infusion daily on Days 1-5 of each 4 week treatment cycle, and imatinib mesylate (Gleevec) by mouth with a daily dose of 400 mg for participants in the chronic phase of chronic myeloid leukemia (CML) or 600 mg for participants in the accelerated or blast phase of CML.
Measure Participants	0

3. Primary Outcome

Title	Number of Participants With Adverse Experiences (AEs)
Description	Summary of participants who had adverse events (AEs), who discontinued treatment due to the AE, who had serious adverse events (SAEs), and who had SAEs that were related to treatments. A serious adverse event is one that at any dose of the study drug or at any time during the period of observation: Results in death; Is life threatening; Requires inpatient hospitalization or prolongation of existing hospitalization; Results in persistent or significant disability/incapacity; Is a congenital anomaly/birth defect; Is medically important. The Investigator assessed each AE for potential causal relationship between the event and study drug. An investigator assessment of possibly, probably or unknown relation is considered related.
Time Frame	up to 3 years

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Homoharringtonine + Imatinib Mesylate
Arm/Group Description	Participants are administered homoharringtonine (omacetaxine) 2.5 mg/m^2 by continuous 24-hour intravenous infusion daily on Days 1-5 of each 4 week treatment cycle, and imatinib mesylate (Gleevec) by mouth with a daily dose of 400 mg for participants in the chronic phase of chronic myeloid leukemia (CML) or 600 mg for participants in the accelerated or blast phase of CML.
Measure Participants	15
AEs	15 100%
Discontinued due to AE	2 13.3%
Serious AEs	12 80%
SAEs considered related	7 46.7%

4. Secondary Outcome

Title	Participants With Complete Hematologic Remission Suppression of the Philadelphia Chromosome
Description	Complete hematologic remission was further classified according to the suppression of the Philadelphia chromosome (Ph) as: No cytogenetic response - Ph positive 100% Minimal cytogenetic response - Ph positive 35-90% Partial cytogenetic response - Ph positive 1-34% Complete cytogenetic response - Ph positive 0%
Time Frame	up to month 4

Outcome Measure Data

Analysis Population Description

No participants were analyzed since the study was intended to follow a Simon two stage design to test 18 participants in each stratum (chronic, accelerated and blast phases) for efficacy. Enrollment was insufficient.

Arm/Group Title	Homoharringtonine + Imatinib Mesylate
Arm/Group Description	Participants are administered homoharringtonine (omacetaxine) 2.5 mg/m^2 by continuous 24-hour intravenous infusion daily on Days 1-5 of each 4 week treatment cycle, and imatinib mesylate (Gleevec) by mouth with a daily dose of 400 mg for participants in the chronic phase of chronic myeloid leukemia (CML) or 600 mg for participants in the accelerated or blast phase of CML.
Measure Participants	0

Adverse Events

Time Frame	Day 1 up to 3 years (30 days past last dose)
Arm/Group Title	Homoharringtonine + Imatinib Mesylate
Arm/Group Description	Participants are administered homoharringtonine (omacetaxine) 2.5 mg/m^2 by continuous 24-hour intravenous infusion daily on Days 1-5 of each 4 week treatment cycle, and imatinib mesylate (Gleevec) by mouth with a daily dose of 400 mg for participants in the chronic phase of chronic myeloid leukemia (CML) or 600 mg for participants in the accelerated or blast phase of CML.
All Cause Mortality
	Homoharringtonine + Imatinib Mesylate
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Homoharringtonine + Imatinib Mesylate
	Affected / at Risk (%)	# Events
Total	12/15 (80%)
Blood and lymphatic system disorders
Neutropenic fever	3/15 (20%)
Febrile neutropenia	1/15 (6.7%)
Cardiac disorders
Atrial fibrillation	1/15 (6.7%)
Gastrointestinal disorders
Gastrointestinal bleeding	1/15 (6.7%)
Hemorrhage, gastrointestinal	1/15 (6.7%)
General disorders
Fever	2/15 (13.3%)
Infection	1/15 (6.7%)
Weakness	1/15 (6.7%)
Sudden death	1/15 (6.7%)
Death	1/15 (6.7%)
Injury, poisoning and procedural complications
Fatal car accident	1/15 (6.7%)
Investigations
Leukocytosis	1/15 (6.7%)
Musculoskeletal and connective tissue disorders
Bone pain	1/15 (6.7%)
Pain, upper extremities	1/15 (6.7%)
Pain, low back	1/15 (6.7%)
Nervous system disorders
Dizziness	1/15 (6.7%)
Renal and urinary disorders
Renal failure	1/15 (6.7%)
Acute renal failure	1/15 (6.7%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/15 (6.7%)
Vascular disorders
Cerebral vascular event (fatal)	1/15 (6.7%)
Hypotension	2/15 (13.3%)
Intra-cranial hemorrhage	1/15 (6.7%)
Other (Not Including Serious) Adverse Events
	Homoharringtonine + Imatinib Mesylate
	Affected / at Risk (%)	# Events
Total	15/15 (100%)
Blood and lymphatic system disorders
Anemia	9/15 (60%)
Bruising	1/15 (6.7%)
Abdominal bruising, secondary to SC injections	2/15 (13.3%)
Decreased prothrombinemia	1/15 (6.7%)
Ecchymoses, mouth and arms	1/15 (6.7%)
Hematoma	1/15 (6.7%)
Hepatitis A	1/15 (6.7%)
Hypertriglyceridemia	1/15 (6.7%)
Intermittent anemia	1/15 (6.7%)
Myelosuppression	5/15 (33.3%)
Neutropenia	8/15 (53.3%)
Neutropenic fever	2/15 (13.3%)
Nosebleed	2/15 (13.3%)
Pancytopenia	3/15 (20%)
Petechiae	2/15 (13.3%)
Petechiae abdomen	1/15 (6.7%)
Petechiae head, arms, neck, oral	1/15 (6.7%)
Petechiae thigh	1/15 (6.7%)
Thrombocytopenia	8/15 (53.3%)
Thrombocytopenia, intermittent	5/15 (33.3%)
Ear and labyrinth disorders
Worsening otitis media	1/15 (6.7%)
Eye disorders
Conjunctival melanosis	1/15 (6.7%)
Itchy eyes	1/15 (6.7%)
Gastrointestinal disorders
Fluid retention	2/15 (13.3%)
Abdominal bloating	1/15 (6.7%)
Abdominal discomfort intermittent	1/15 (6.7%)
Abdominal pain	3/15 (20%)
Abdominal pain, interrmittent left sided	1/15 (6.7%)
Anorexia	1/15 (6.7%)
Colon polyps	2/15 (13.3%)
Constipation	2/15 (13.3%)
Constipation, intermittent	1/15 (6.7%)
Diarrhea	7/15 (46.7%)
Dry heaves	1/15 (6.7%)
Flatus	1/15 (6.7%)
Gastritis	1/15 (6.7%)
GERD	1/15 (6.7%)
Hemorrhoids	1/15 (6.7%)
Hepatic Dysfunction	1/15 (6.7%)
Indigestion	1/15 (6.7%)
Lack of appetite	1/15 (6.7%)
Poor appetite	2/15 (13.3%)
Suppressed appetite	1/15 (6.7%)
Loose stools	3/15 (20%)
Melena	1/15 (6.7%)
Mild nausea	1/15 (6.7%)
Nausea	8/15 (53.3%)
Nausea, intermittent	1/15 (6.7%)
Pandiverticulosis	1/15 (6.7%)
Rectal bleeding	1/15 (6.7%)
Renal failure	1/15 (6.7%)
Stomach discomfort	1/15 (6.7%)
Upset stomach	1/15 (6.7%)
Vomiting	11/15 (73.3%)
Vomiting, occasional	1/15 (6.7%)
General disorders
Allergies	1/15 (6.7%)
Bacteremia	1/15 (6.7%)
Bleeding at CVC site	1/15 (6.7%)
Bleeding at PICC line insertion site	1/15 (6.7%)
Bleeding at port site	1/15 (6.7%)
Bruising	2/15 (13.3%)
Chills	2/15 (13.3%)
Chills, intermittent	1/15 (6.7%)
Citrobacter freundii positive	1/15 (6.7%)
Fatigue	7/15 (46.7%)
Mild fatigue	4/15 (26.7%)
Severe fatigue	1/15 (6.7%)
Fever	2/15 (13.3%)
Fibromyalgia syndrome	1/15 (6.7%)
Generalized achiness	1/15 (6.7%)
Intermittent fatigue	1/15 (6.7%)
Intermittent fever	1/15 (6.7%)
Mild fever	1/15 (6.7%)
Pain, left flank	1/15 (6.7%)
Pain, left upper quadrant	1/15 (6.7%)
Pain, right hip	1/15 (6.7%)
Pallor	1/15 (6.7%)
Runny nose	1/15 (6.7%)
Weakness	1/15 (6.7%)
Mildly weak	1/15 (6.7%)
Edema	2/15 (13.3%)
Edema, intermittent	1/15 (6.7%)
Edema, pedal	1/15 (6.7%)
Edema, ankle	2/15 (13.3%)
Edema, bilateral	1/15 (6.7%)
Edema, bilateral pedal	1/15 (6.7%)
Edema, bilateral legs + 2 pitting	1/15 (6.7%)
Edema, bilateral lower extremity	3/15 (20%)
Edema, lower extremity	2/15 (13.3%)
Edema, peripheral	2/15 (13.3%)
Edema, Intermittent trace peripheral	1/15 (6.7%)
Palpitations	1/15 (6.7%)
Periorbital edema	1/15 (6.7%)
Right Arm Swelling	1/15 (6.7%)
Right side face swelling	1/15 (6.7%)
Swelling, hands and feet	1/15 (6.7%)
Swelling, right arm	1/15 (6.7%)
Bleeding gums	4/15 (26.7%)
Gum soreness	1/15 (6.7%)
Gum tenderness	1/15 (6.7%)
Lip bleeding	1/15 (6.7%)
Loss of taste	1/15 (6.7%)
Malodor, secondary to right groin hematoma	1/15 (6.7%)
Mucositis	1/15 (6.7%)
Oral ulcer	1/15 (6.7%)
Right Ear Pressure	1/15 (6.7%)
Sinus drainage	1/15 (6.7%)
Throat pain	1/15 (6.7%)
Infections and infestations
Infection, Staphylococcus aureus	1/15 (6.7%)
Pseudomonas aeruginosa	1/15 (6.7%)
Staph infection right nostril	1/15 (6.7%)
Investigations
Hemoglobin decreased	1/15 (6.7%)
Leukocytosis	1/15 (6.7%)
Severe thrombocytopenia	1/15 (6.7%)
Elevated BUN	1/15 (6.7%)
Elevated PTT	1/15 (6.7%)
Decreased hemaglobin	1/15 (6.7%)
Elevated creatinine	1/15 (6.7%)
Elevated LDH	1/15 (6.7%)
Metabolism and nutrition disorders
Decreased appetite	2/15 (13.3%)
Dehydration	1/15 (6.7%)
Goiter, nodular	1/15 (6.7%)
Hot flashes	1/15 (6.7%)
Hyperglycemia	1/15 (6.7%)
Hyperphosphatemia	2/15 (13.3%)
Hypermagnesemia	1/15 (6.7%)
Hypokalemia	4/15 (26.7%)
Hypomagnesemia	4/15 (26.7%)
Hypomagnesium	2/15 (13.3%)
Uricemia	1/15 (6.7%)
Musculoskeletal and connective tissue disorders
Aching all over	1/15 (6.7%)
Bilateral upper pain - extremities	1/15 (6.7%)
Cellulitis, left arm	1/15 (6.7%)
Chest pain	1/15 (6.7%)
Chest pressure	1/15 (6.7%)
Cramps right leg, right arm	1/15 (6.7%)
Cramps, muscle	1/15 (6.7%)
Cramps, neck	1/15 (6.7%)
Cramps, pedal muscle bilateral	1/15 (6.7%)
Dental abscesses	1/15 (6.7%)
Diffused bone pain	1/15 (6.7%)
Left hip and leg pain, secondary to bone marrow aspiration	1/15 (6.7%)
Leg muscle soreness	1/15 (6.7%)
Leg trembling on standing	1/15 (6.7%)
Pain, bilateral knee	1/15 (6.7%)
Pain, bilateral shoulder	2/15 (13.3%)
Pain, bone	2/15 (13.3%)
Pain, knee	1/15 (6.7%)
Pain, left knee	1/15 (6.7%)
Pain, left great toe	1/15 (6.7%)
Pain, low back	1/15 (6.7%)
Pain, muscle	1/15 (6.7%)
Pain, back and shoulder	1/15 (6.7%)
Pain, neck	1/15 (6.7%)
Pain, upper extremities	1/15 (6.7%)
Teeth sensitivity	1/15 (6.7%)
Tooth pain	1/15 (6.7%)
Nervous system disorders
Anxiety	1/15 (6.7%)
Bad dreams	1/15 (6.7%)
Confusion	1/15 (6.7%)
Mild confusion	1/15 (6.7%)
Dizziness	1/15 (6.7%)
Dizziness, fentanyl	1/15 (6.7%)
Dysphagia	1/15 (6.7%)
Headache	6/15 (40%)
Headache/migraine, intermittent right side	1/15 (6.7%)
Headache, sinus	1/15 (6.7%)
Insomnia	1/15 (6.7%)
Light headed	2/15 (13.3%)
Neuropathy, bipedal	1/15 (6.7%)
Neuropathy, hands and feet	1/15 (6.7%)
Peripheral neuropathy, secondary to diabetes	1/15 (6.7%)
Night sweats	2/15 (13.3%)
Numbness, toe	1/15 (6.7%)
Numbness/tingling in extremities	1/15 (6.7%)
Syncope	1/15 (6.7%)
Renal and urinary disorders
Dark urine	1/15 (6.7%)
Urinary tract infection	3/15 (20%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	1/15 (6.7%)
Cough	5/15 (33.3%)
Dry throat	1/15 (6.7%)
Dyspnea	3/15 (20%)
Klebsiella pneumonia	1/15 (6.7%)
Pleural effusion	1/15 (6.7%)
Pneumonia	1/15 (6.7%)
Pulmonary edema	1/15 (6.7%)
Respiratory infection	1/15 (6.7%)
Short of breath	2/15 (13.3%)
Shortness of breath on exertion	1/15 (6.7%)
Sinus congestion	2/15 (13.3%)
Sinus pain	1/15 (6.7%)
Nasal congestion intermittent, secondary to allergies	2/15 (13.3%)
Sore throat	2/15 (13.3%)
Upper respiratory infection	2/15 (13.3%)
Upper respiratory infection nasal allergies	1/15 (6.7%)
Allergic rhinitis	1/15 (6.7%)
Skin and subcutaneous tissue disorders
Acanthosis nigricans	1/15 (6.7%)
Bruising skin	1/15 (6.7%)
Dry skin	1/15 (6.7%)
Erythema, left foot	1/15 (6.7%)
Erythema, tonsils	1/15 (6.7%)
Hypopigmentation facial	1/15 (6.7%)
Itching due to transfusion	1/15 (6.7%)
Itching impaired	1/15 (6.7%)
Generalized skin itching	2/15 (13.3%)
Itchy ears	1/15 (6.7%)
Keratoderma, pedal	1/15 (6.7%)
Pedal calluses	1/15 (6.7%)
Mild rash	1/15 (6.7%)
Mouth sores	1/15 (6.7%)
Mouth sores, intermittent	1/15 (6.7%)
Mouth ulcerations	1/15 (6.7%)
Oral white patches	1/15 (6.7%)
Peeling skin, groin	1/15 (6.7%)
Plantar surface skin sensitive	1/15 (6.7%)
Rash	1/15 (6.7%)
Painful, red, swollen rash	1/15 (6.7%)
Rash abdomen	1/15 (6.7%)
Rash, macular / facial	1/15 (6.7%)
Seborrheic keratosis, upper extremity	1/15 (6.7%)
Skin nodule	1/15 (6.7%)
Swelling, face	1/15 (6.7%)
Tinea	1/15 (6.7%)
Punctate lesion right foot dorsom	1/15 (6.7%)
Vesicular lesions, right buttock	1/15 (6.7%)
Yeast infection, buttock	1/15 (6.7%)
Surgical and medical procedures
Dental extraction	1/15 (6.7%)

Limitations/Caveats

This study was intended to follow a Simon two stage design to test 18 patients in each stratum (chronic, accelerated and blast phase) for efficacy. Only 15 were enrolled, an insufficient number for a formal statistical analysis of efficacy.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.