Clofarabine-Melphalan-Alemtuzumab Conditioning in Patients With Advanced Hematologic Malignancies

• Sponsor: University of Chicago (Other)
• Overall Status: Completed
• CT.gov ID: NCT00943592
• Collaborator: (none)
• Enrollment: 82
• Location: 1
• Arm: 1
• Duration (Months): 92.1
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

This is a clinical research study designed to evaluate whether a conditioning regimen consisting of the combination of three drugs named melphalan, alemtuzumab and clofarabine supported by donor blood cells will result in rapid recovery and a high rate of long-lasting remissions in patients with leukemia, lymphoma and myeloma.

Condition or Disease	Intervention/Treatment	Phase
Advanced Hematologic Malignancies; Leukemia; Preleukemia	Drug: Clofarabine; Drug: Melphalan; Drug: Campath; Procedure: Stem Cell Transplant	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 82 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Clofarabine-melphalan-alemtuzumab Conditioning in Patients With Advanced Hematologic Malignancies
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment	Drug: Clofarabine; Clofarabine will be administered as a 2-hour IV infusion on Days 1 through 5 at approximately the same time everyday (4 dose levels).; Drug: Melphalan; Doses ranging from 100 to 140 mg/m2; Drug: Campath; 20mg/d x5; Procedure: Stem Cell Transplant; Infusion of donor, bone marrow and auto.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Hepatic Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation [Day 7 until Day 30]

   Toxicity was scored according to NCI/CTC version 3

2. Number of Participants With Renal Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation [Day 7 until Day 30]

   Toxicity was scored according to NCI/CTC version 3

3. Number of Participants With Skin Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation [Day 7 until Day 30]

   Toxicity was scored according to NCI/CTC version 3

4. Number of Participants With Other Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation [Day 7 until Day 30]

   Toxicity was scored according to NCI/CTC version 3

Secondary Outcome Measures

1. Overall Survival (OS) [1 year]

2. Progression-free Survival (PFS) [1 year]

   Progression is defined from stem cell infusion to disease relapse, i.e., recurrence of hematologic malignancy and/or need for treatment after transplant for disease or death from any cause, whichever occurred first.

3. Treatment-related Mortality (TRM) [1 year]

4. Relapse Rate [1 year]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Relapsed or refractory acute myelogenous or lymphoid leukemia

• Chronic myelogenous leukemia in accelerated phase or blast-crisis

• Chronic myelogenous leukemia in second or subsequent chronic phase

• Recurrent or refractory malignant lymphoma or Hodgkin's disease

• Multiple myeloma at high risk for disease recurrence

• Chronic lymphocytic leukemia, relapsed or with poor prognostic features

• Other Myeloproliferative disorder (polycythemia vera, essential thrombocythemia, myelofibrosis) with poor prognostic features

• Myelodysplastic syndromes (including PNH) with > 5% blasts

• Zubroid performance status < 2 (See Appendix B)

• Life expectancy is not severely limited by concomitant illness

• Adequate cardiac and pulmonary function. Patients with decreased LVEF or PFTS will be evaluated by cardiology or pulmonary prior to enrollment on this protocol

• Calculated Creatinine Clearance > 50 ml/min

• Serum bilirubin 2.0 mg/dl, SGPT < 3x upper limit of normal

• No evidence of chronic active hepatitis or cirrhosis

• HIV-negative

• Patient is not pregnant

• Patient or guardian able to sign informed consent

Exclusion Criteria:

• Clinical progression

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Chicago	Chicago	Illinois	United States	60637

Sponsors and Collaborators

• University of Chicago

Investigators

• Principal Investigator: Andrew Artz, MD, University of Chicago

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Chicago
• ClinicalTrials.gov Identifier: NCT00943592
• Other Study ID Numbers: 14341B; NCT00572546
• First Posted: Jul 22, 2009
• Last Update Posted: Feb 27, 2014
• Last Verified: Jan 1, 2014

• Keywords provided by University of Chicago: Melphalan; Alemtuzumab; Clofarabine
• Additional relevant MeSH terms: Neoplasms; Hematologic Neoplasms; Preleukemia; Melphalan; Alemtuzumab; Clofarabine

Study Results

Participant Flow

Arm/Group Title	Clofarabine, Melphalan, and Alemtuzumab
Arm/Group Description	Clofarabine was initially administered IV infusion over 1 hour on days -7 through -3 (4 dose levels from 10 to 40 mg/m2); subsequently, the protocol was amended to infuse clofarabine over 3 hours. Melphalan (doses ranging from 100 to 140 mg/m2) was infused over 30 minutes on day -2. Alemtuzumab was administered at 20 mg IV infusion on day -7 through day -3 over 1 hour.
Period Title: Overall Study
STARTED	82
Maximum Tolerated Dose	74
COMPLETED	79
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Clofarabine, Melphalan, and Alemtuzumab
Arm/Group Description	Clofarabine was initially administered IV infusion over 1 hour on days -7 through -3 (4 dose levels from 10 to 40 mg/m2); subsequently, the protocol was amended to infuse clofarabine over 3 hours. Melphalan (doses ranging from 100 to 140 mg/m2) was infused over 30 minutes on day -2. Alemtuzumab was administered at 20 mg IV infusion on day -7 through day -3 over 1 hour.
Overall Participants	82
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	54
Sex: Female, Male (Count of Participants)
Female	33 40.2%
Male	49 59.8%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Hepatic Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation
Description	Toxicity was scored according to NCI/CTC version 3
Time Frame	Day 7 until Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clofarabine, Melphalan, and Alemtuzumab
Arm/Group Description	Clofarabine was initially administered IV infusion over 1 hour on days -7 through -3 (4 dose levels from 10 to 40 mg/m2); subsequently, the protocol was amended to infuse clofarabine over 3 hours. Melphalan (doses ranging from 100 to 140 mg/m2) was infused over 30 minutes on day -2. Alemtuzumab was administered at 20 mg IV infusion on day -7 through day -3 over 1 hour.
Measure Participants	82
Grade 1-2	48 58.5%
Grade 3-4	30 36.6%

2. Secondary Outcome

Title	Overall Survival (OS)
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

74 patients received the Maximum Tolerated Dose of clofarabine 40 mg/m2 IV daily x 5 days, melphalan 140 mg/m2 x 1 day, and alemtuzumab 20 mg IV daily x 5 days

Arm/Group Title	Clofarabine, Melphalan, and Alemtuzumab
Arm/Group Description	Clofarabine was initially administered IV infusion over 1 hour on days -7 through -3 (4 dose levels from 10 to 40 mg/m2); subsequently, the protocol was amended to infuse clofarabine over 3 hours. Melphalan (doses ranging from 100 to 140 mg/m2) was infused over 30 minutes on day -2. Alemtuzumab was administered at 20 mg IV infusion on day -7 through day -3 over 1 hour.
Measure Participants	74
Number (95% Confidence Interval) [percentage of participants]	59 72%

3. Primary Outcome

Title	Number of Participants With Renal Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation
Description	Toxicity was scored according to NCI/CTC version 3
Time Frame	Day 7 until Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clofarabine, Melphalan, and Alemtuzumab
Arm/Group Description	Clofarabine was initially administered IV infusion over 1 hour on days -7 through -3 (4 dose levels from 10 to 40 mg/m2); subsequently, the protocol was amended to infuse clofarabine over 3 hours. Melphalan (doses ranging from 100 to 140 mg/m2) was infused over 30 minutes on day -2. Alemtuzumab was administered at 20 mg IV infusion on day -7 through day -3 over 1 hour.
Measure Participants	82
Grade 1-2	26 31.7%
Grade 3-4	13 15.9%
Grade 5	3 3.7%

4. Primary Outcome

Title	Number of Participants With Skin Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation
Description	Toxicity was scored according to NCI/CTC version 3
Time Frame	Day 7 until Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clofarabine, Melphalan, and Alemtuzumab
Arm/Group Description	Clofarabine was initially administered IV infusion over 1 hour on days -7 through -3 (4 dose levels from 10 to 40 mg/m2); subsequently, the protocol was amended to infuse clofarabine over 3 hours. Melphalan (doses ranging from 100 to 140 mg/m2) was infused over 30 minutes on day -2. Alemtuzumab was administered at 20 mg IV infusion on day -7 through day -3 over 1 hour.
Measure Participants	82
Grade 1-2	6 7.3%
Grade 3-4	8 9.8%

5. Primary Outcome

Title	Number of Participants With Other Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation
Description	Toxicity was scored according to NCI/CTC version 3
Time Frame	Day 7 until Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clofarabine, Melphalan, and Alemtuzumab
Arm/Group Description	Clofarabine was initially administered IV infusion over 1 hour on days -7 through -3 (4 dose levels from 10 to 40 mg/m2); subsequently, the protocol was amended to infuse clofarabine over 3 hours. Melphalan (doses ranging from 100 to 140 mg/m2) was infused over 30 minutes on day -2. Alemtuzumab was administered at 20 mg IV infusion on day -7 through day -3 over 1 hour.
Measure Participants	82
Grade 1-2	12 14.6%
Grade 3-4	7 8.5%
Grade 5	7 8.5%

6. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	Progression is defined from stem cell infusion to disease relapse, i.e., recurrence of hematologic malignancy and/or need for treatment after transplant for disease or death from any cause, whichever occurred first.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

74 patients received the Maximum Tolerated Dose of clofarabine 40 mg/m2 IV daily x 5 days, melphalan 140 mg/m2 x 1 day, and alemtuzumab 20 mg IV daily x 5 days

Arm/Group Title	Clofarabine, Melphalan, and Alemtuzumab
Arm/Group Description	Clofarabine was initially administered IV infusion over 1 hour on days -7 through -3 (4 dose levels from 10 to 40 mg/m2); subsequently, the protocol was amended to infuse clofarabine over 3 hours. Melphalan (doses ranging from 100 to 140 mg/m2) was infused over 30 minutes on day -2. Alemtuzumab was administered at 20 mg IV infusion on day -7 through day -3 over 1 hour.
Measure Participants	74
Number (95% Confidence Interval) [percentage of participants]	45 54.9%

7. Secondary Outcome

Title	Treatment-related Mortality (TRM)
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

74 patients received the Maximum Tolerated Dose of clofarabine 40 mg/m2 IV daily x 5 days, melphalan 140 mg/m2 x 1 day, and alemtuzumab 20 mg IV daily x 5 days

Arm/Group Title	Clofarabine, Melphalan, and Alemtuzumab
Arm/Group Description	Clofarabine was initially administered IV infusion over 1 hour on days -7 through -3 (4 dose levels from 10 to 40 mg/m2); subsequently, the protocol was amended to infuse clofarabine over 3 hours. Melphalan (doses ranging from 100 to 140 mg/m2) was infused over 30 minutes on day -2. Alemtuzumab was administered at 20 mg IV infusion on day -7 through day -3 over 1 hour.
Measure Participants	74
Number (95% Confidence Interval) [percentage of participants]	26 31.7%

8. Secondary Outcome

Title	Relapse Rate
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

74 patients received the Maximum Tolerated Dose of clofarabine 40 mg/m2 IV daily x 5 days, melphalan 140 mg/m2 x 1 day, and alemtuzumab 20 mg IV daily x 5 days

Arm/Group Title	Clofarabine, Melphalan, and Alemtuzumab
Arm/Group Description	Clofarabine was initially administered IV infusion over 1 hour on days -7 through -3 (4 dose levels from 10 to 40 mg/m2); subsequently, the protocol was amended to infuse clofarabine over 3 hours. Melphalan (doses ranging from 100 to 140 mg/m2) was infused over 30 minutes on day -2. Alemtuzumab was administered at 20 mg IV infusion on day -7 through day -3 over 1 hour.
Measure Participants	74
Number (95% Confidence Interval) [percentage of participants]	29 35.4%

Adverse Events

Arm/Group Title	Clofarabine, Melphalan, and Alemtuzumab
Arm/Group Description	Clofarabine was initially administered IV infusion over 1 hour on days -7 through -3 (4 dose levels from 10 to 40 mg/m2); subsequently, the protocol was amended to infuse clofarabine over 3 hours. Melphalan (doses ranging from 100 to 140 mg/m2) was infused over 30 minutes on day -2. Alemtuzumab was administered at 20 mg IV infusion on day -7 through day -3 over 1 hour.
All Cause Mortality
	Clofarabine, Melphalan, and Alemtuzumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Clofarabine, Melphalan, and Alemtuzumab
	Affected / at Risk (%)	# Events
Total	44/82 (53.7%)
Cardiac disorders
Atrial fibrillation	2/82 (2.4%)	2
Cardiovascular disease, unspecified	2/82 (2.4%)	2
General disorders
Mucositis	1/82 (1.2%)	1
Hepatobiliary disorders
Hepatobiliary disease NOS	30/82 (36.6%)	30
Immune system disorders
Anaphylactic reaction	1/82 (1.2%)	1
Psychiatric disorders
Confusion	1/82 (1.2%)	1
Mental status changes	4/82 (4.9%)	4
Renal and urinary disorders
Renal disorder NOS	16/82 (19.5%)	16
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/82 (1.2%)	1
Pulmonary hemorrhage	1/82 (1.2%)	1
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrome	8/82 (9.8%)	8
Vascular disorders
Hypotension	1/82 (1.2%)	1
Other (Not Including Serious) Adverse Events
	Clofarabine, Melphalan, and Alemtuzumab
	Affected / at Risk (%)	# Events
Total	62/82 (75.6%)
Cardiac disorders
Atrial flutter	1/82 (1.2%)	1
Gastrointestinal disorders
Pancreatitis	2/82 (2.4%)	2
Diarrhea	1/82 (1.2%)	1
General disorders
Mucositis	3/82 (3.7%)	3
Hepatobiliary disorders
Hepatobiliary disease NOS	48/82 (58.5%)	48
Nervous system disorders
Pseudotumor cerebri	1/82 (1.2%)	1
Psychiatric disorders
Anxiety	1/82 (1.2%)	1
Confusion	1/82 (1.2%)	1
Renal and urinary disorders
Renal disorder NOS	26/82 (31.7%)	26
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrome	6/82 (7.3%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.