Trial Outcomes & Findings for Clofarabine-Melphalan-Alemtuzumab Conditioning in Patients With Advanced Hematologic Malignancies (NCT NCT00943592)

NCT ID: NCT00943592

Last Updated: 2014-02-27

Results Overview

Toxicity was scored according to NCI/CTC version 3

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 82 participants
• Primary outcome timeframe: Day 7 until Day 30
• Results posted on: 2014-02-27

Participant Flow

Participant milestones

Measure	Clofarabine, Melphalan, and Alemtuzumab 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 Study STARTED	82
Overall Study Maximum Tolerated Dose	74
Overall Study COMPLETED	79
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure

Clofarabine, Melphalan, and Alemtuzumab 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 Study Death

3

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Clofarabine, Melphalan, and Alemtuzumab n=82 Participants 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.
Age, Continuous	54 years n=5 Participants
Sex: Female, Male Female	33 Participants n=5 Participants
Sex: Female, Male Male	49 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 7 until Day 30

Toxicity was scored according to NCI/CTC version 3

Outcome measures

Measure	Clofarabine, Melphalan, and Alemtuzumab n=82 Participants 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.
Number of Participants With Hepatic Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation Grade 1-2	48 participants
Number of Participants With Hepatic Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation Grade 3-4	30 participants

PRIMARY outcome

Timeframe: Day 7 until Day 30

Toxicity was scored according to NCI/CTC version 3

Outcome measures

Measure	Clofarabine, Melphalan, and Alemtuzumab n=82 Participants 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.
Number of Participants With Renal Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation Grade 1-2	26 participants
Number of Participants With Renal Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation Grade 3-4	13 participants
Number of Participants With Renal Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation Grade 5	3 participants

PRIMARY outcome

Timeframe: Day 7 until Day 30

Toxicity was scored according to NCI/CTC version 3

Outcome measures

Measure	Clofarabine, Melphalan, and Alemtuzumab n=82 Participants 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.
Number of Participants With Skin Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation Grade 1-2	6 participants
Number of Participants With Skin Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation Grade 3-4	8 participants

PRIMARY outcome

Timeframe: Day 7 until Day 30

Toxicity was scored according to NCI/CTC version 3

Outcome measures

Measure	Clofarabine, Melphalan, and Alemtuzumab n=82 Participants 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.
Number of Participants With Other Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation Grade 3-4	7 participants
Number of Participants With Other Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation Grade 1-2	12 participants
Number of Participants With Other Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation Grade 5	7 participants

SECONDARY outcome

Timeframe: 1 year

Population: 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

Outcome measures

Measure

Clofarabine, Melphalan, and Alemtuzumab n=74 Participants 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 Survival (OS)

59 percentage of participants Interval 47.0 to 71.0

SECONDARY outcome

Timeframe: 1 year

Population: 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

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.

Outcome measures

Measure

Clofarabine, Melphalan, and Alemtuzumab n=74 Participants 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.

Progression-free Survival (PFS)

45 percentage of participants Interval 33.0 to 67.0

SECONDARY outcome

Timeframe: 1 year

Population: 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

Outcome measures

Measure

Clofarabine, Melphalan, and Alemtuzumab n=74 Participants 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.

Treatment-related Mortality (TRM)

26 percentage of participants Interval 16.0 to 36.0

SECONDARY outcome

Timeframe: 1 year

Population: 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

Outcome measures

Measure

Clofarabine, Melphalan, and Alemtuzumab n=74 Participants 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.

Relapse Rate

29 percentage of participants Interval 18.0 to 40.0

Adverse Events

Clofarabine, Melphalan, and Alemtuzumab

Serious events: 44 serious events

Other events: 62 other events

Deaths: 0 deaths

Serious adverse events

Measure	Clofarabine, Melphalan, and Alemtuzumab n=82 participants at risk 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.
Immune system disorders Anaphylactic reaction	1.2% 1/82 • Number of events 1
Cardiac disorders Atrial fibrillation	2.4% 2/82 • Number of events 2
Cardiac disorders Cardiovascular disease, unspecified	2.4% 2/82 • Number of events 2
Psychiatric disorders Confusion	1.2% 1/82 • Number of events 1
Vascular disorders Hypotension	1.2% 1/82 • Number of events 1
Psychiatric disorders Mental status changes	4.9% 4/82 • Number of events 4
General disorders Mucositis	1.2% 1/82 • Number of events 1
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.2% 1/82 • Number of events 1
Respiratory, thoracic and mediastinal disorders Pulmonary hemorrhage	1.2% 1/82 • Number of events 1
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	9.8% 8/82 • Number of events 8
Renal and urinary disorders Renal disorder NOS	19.5% 16/82 • Number of events 16
Hepatobiliary disorders Hepatobiliary disease NOS	36.6% 30/82 • Number of events 30

Other adverse events

Measure	Clofarabine, Melphalan, and Alemtuzumab n=82 participants at risk 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.
Psychiatric disorders Anxiety	1.2% 1/82 • Number of events 1
Cardiac disorders Atrial flutter	1.2% 1/82 • Number of events 1
Psychiatric disorders Confusion	1.2% 1/82 • Number of events 1
Hepatobiliary disorders Hepatobiliary disease NOS	58.5% 48/82 • Number of events 48
General disorders Mucositis	3.7% 3/82 • Number of events 3
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	7.3% 6/82 • Number of events 6
Gastrointestinal disorders Pancreatitis	2.4% 2/82 • Number of events 2
Renal and urinary disorders Renal disorder NOS	31.7% 26/82 • Number of events 26
Gastrointestinal disorders Diarrhea	1.2% 1/82 • Number of events 1
Nervous system disorders Pseudotumor cerebri	1.2% 1/82 • Number of events 1

Additional Information

Dr. Andrew Artz

University of Chicago

Phone: 773-834-8980

Email: aartz@medicine.bsd.uchicago.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place