Alemtuzumab and Pentostatin In T-cell Neoplasms

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00453193
• Collaborator: Astex Pharmaceuticals, Inc. (Industry), Bayer (Industry)
• Enrollment: 26
• Location: 1
• Arm: 1
• Duration (Months): 65.9
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to learn if giving pentostatin with alemtuzumab can help to control T-cell malignancy. The safety of this combination therapy will also be studied.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma; Leukemia	Drug: Pentostatin; Drug: Alemtuzumab	Phase 2

Detailed Description

Alemtuzumab is an antibody protein that is directed towards a marker molecule on the surface of both B- and T- lymphoid cells. It is currently approved for use in treating patients with chronic lymphocytic leukemia and has been studied in treating patients with a number of T-cell malignancies. Alemtuzumab has been found to be effective in these conditions. Pentostatin is a drug that is approved for treating patients with hairy cell leukemia, a B-cell malignancy. Pentostatin has also been studied in a number of T-cell cancers and has been found to be effective. The purpose of this study is to see whether combining these drugs will prove to be more effective.

If you are found to be eligible to take part in this study, you will receive pentostatin through a central venous catheter in your vein once a week for 4 weeks and then every 2 weeks until the achievement of best response. A central venous catheter is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. Your physician will explain this procedure to you in more detail and you will be required to sign a separate consent form for this procedure.

Alemtuzumab will also be given through a vein catheter on Days 1, 2, and 3. The dose of alemtuzumab that you receive will be increased each day for the first 3 days to make sure that you tolerate it. It will then be given three times per week until you achieve the best response. If you develop reactions to alemtuzumab when given through a vein, you may receive it by injections of the same dose under the skin.

During the treatment, you will have blood (about 2 tablespoons) drawn once a week for the first 4 weeks for routine blood tests. These blood tests will then be repeated every 2 to 4 weeks for the remainder of the study. At the end of treatment a bone marrow examination will be repeated to document your response. Also, if you had a chest X-ray or CT scans, these will be repeated to confirm your level of response.

The maximum amount of time that alemtuzumab will be given is 3 months. The maximum amount of time that pentostatin will be given is 6 months. You may be able to receive the treatment will your local oncologists. However, you will have close follow-up at M. D. Anderson. You will be taken off this treatment if the disease gets worse during treatment or if unacceptable side effects develop.

You will be continued to be followed either directly or by telephone to evaluate your long-term response to treatment on this study.

This is an investigational study. Both alemtuzumab and pentostatin are commercially approved drugs that have been used to treat T-cell malignancies. A total of 60 patients will take part in this study. All will be enrolled at M. D. Anderson.

This is an investigational study. Both alemtuzumab and pentostatin are commercially approved drugs that have been used to treat T-cell malignancies. A total of 60 patients will take part in this study. All will be enrolled at M. D. Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Alemtuzumab and Pentostatin In T-Cell Neoplasms
• Study Start Date: Sep 1, 2004
• Actual Primary Completion Date: Mar 1, 2010
• Actual Study Completion Date: Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Alemtuzumab + Pentostatin Alemtuzumab 30 mg intravenous (IV) three times weekly; Pentostatin 4 mg/m^2 IV weekly for 4 weeks then every 2 weeks	Drug: Pentostatin; 4 mg/m^2 IV weekly for 4 weeks then every 2 weeks; Other Names: Nipent® ; Drug: Alemtuzumab; 30 mg IV three times weekly; Other Names: Campath CAMPATH-1

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Objective Response [After a maximum of 6 months of therapy maintained for one month.]

   Objective Responses are Complete or Partial Responses: Complete Response defined as disappearance of all evidence of disease detectable by morphology of peripheral blood and bone marrow and computer tomography scanning at the end of therapy, if indicated; and Partial Response as 50% or more reduction in detectable disease, but short of complete response, maintained for 1 month or at least 50% reduction of sum of the products of the diameter of all lesions for 1 month.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age 18 years and older

2. Diagnosis of T lymphoid malignancy established by peripheral blood, bone marrow or tissue (skin, lymph node or other) examination and using the standard criteria.

3. Patients with untreated T-cell-prolymphocytic leukemia (T-PLL), peripheral T-cell lymphoma, hepatosplenic T-cell lymphoma and NK/T cell lymphoma are eligible.

4. Patients with relapsed/refractory T-PLL, T-lineage acute lymphoblastic leukemia (T-ALL), Adult T-cell leukemia/lymphoma (ATLL), peripheral T-cell lymphoma, hepatosplenic T-cell lymphoma and NK/T cell lymphoma and other T-lymphoid malignancies are eligible. Patients who have had prior therapy with either alemtuzumab or pentostatin as single agents are eligible.

5. Willing to use adequate contraception for the entire duration of the study.

6. Performance status 0-2.

7. Creatinine less than or equal to 2.0 mg/dL and calculated creatinine clearance greater than 40

8. Bilirubin less than or equal to 3.0 mg/dL, transaminases (aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT)) less than 4 x upper limit of normal unless related to the disease.

9. Left ventricular ejection fraction greater than 30%.

Exclusion Criteria:

1. Unable or unwilling to sign the consent form.

2. Pregnant or lactating

3. Known to be HIV+

4. Active and uncontrolled infection as judged by treating physician

Contacts and Locations

Locations

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

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Astex Pharmaceuticals, Inc.
• Bayer

Investigators

• Principal Investigator: Farhad Ravandi-Kashani, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• M.D. Andersons website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00453193
• Other Study ID Numbers: 2004-0408
• First Posted: Mar 28, 2007
• Last Update Posted: Aug 7, 2012
• Last Verified: Aug 1, 2012

• Keywords provided by M.D. Anderson Cancer Center: T-Cell Neoplasms; Alemtuzumab; Pentostatin; Campath-1H; Deoxycoformycin; Lymphoma; Leukemia
• Additional relevant MeSH terms: Neoplasms; Alemtuzumab; Pentostatin

Study Results

Participant Flow

Recruitment Details	Recruitment Period: 8/241/2004 to 5/12/2009. All patients registered at The University of Texas M.D. Anderson Cancer Center.
Pre-assignment Detail	Of the 26 enrolled, only 24 patients were included in this study.

Arm/Group Title	Alemtuzumab + Pentostatin
Arm/Group Description	Alemtuzumab 30 mg intravenous (IV) three times weekly; Pentostatin 4 mg/m^2 IV weekly for 4 weeks then every 2 weeks
Period Title: Overall Study
STARTED	24
COMPLETED	24
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Alemtuzumab + Pentostatin
Arm/Group Description	Alemtuzumab 30 mg intravenous (IV) three times weekly; Pentostatin 4 mg/m^2 IV weekly for 4 weeks then every 2 weeks
Overall Participants	24
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	57
Sex: Female, Male (Count of Participants)
Female	10 41.7%
Male	14 58.3%
Region of Enrollment (participants) [Number]
United States	24 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Objective Response
Description	Objective Responses are Complete or Partial Responses: Complete Response defined as disappearance of all evidence of disease detectable by morphology of peripheral blood and bone marrow and computer tomography scanning at the end of therapy, if indicated; and Partial Response as 50% or more reduction in detectable disease, but short of complete response, maintained for 1 month or at least 50% reduction of sum of the products of the diameter of all lesions for 1 month.
Time Frame	After a maximum of 6 months of therapy maintained for one month.

Outcome Measure Data

Analysis Population Description

Analysis was per protocol.

Arm/Group Title	Alemtuzumab + Pentostatin
Arm/Group Description	Alemtuzumab 30 mg intravenous (IV) three times weekly; Pentostatin 4 mg/m^2 IV weekly for 4 weeks then every 2 weeks
Measure Participants	24
Complete Response	11 45.8%
Partial Response	2 8.3%

Adverse Events

Time Frame	5 years 2 months
Arm/Group Title	Alemtuzumab + Pentostatin
Arm/Group Description	Alemtuzumab 30 mg intravenous (IV) three times weekly; Pentostatin 4 mg/m^2 IV weekly for 4 weeks then every 2 weeks
All Cause Mortality
	Alemtuzumab + Pentostatin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Alemtuzumab + Pentostatin
	Affected / at Risk (%)	# Events
Total	15/24 (62.5%)
Blood and lymphatic system disorders
Thrombocytopenia	1/24 (4.2%)	1
Neutropenia	2/24 (8.3%)	2
Subdural Hematoma	1/24 (4.2%)	1
Granulocytopenia	1/24 (4.2%)	1
Epididymitis	1/24 (4.2%)	1
Cardiac disorders
Myocardial Infarction	1/24 (4.2%)	1
General disorders
Death	8/24 (33.3%)	8
fever	1/24 (4.2%)	1
Hepatobiliary disorders
elevated asparatate aminotransferase	1/24 (4.2%)	1
increased liver function	1/24 (4.2%)	1
Infections and infestations
Bacteremia	1/24 (4.2%)	1
Pneumonia	3/24 (12.5%)	4
Neutropenic Fever	1/24 (4.2%)	1
sinusitis	1/24 (4.2%)	1
non neutropenic fever	1/24 (4.2%)	1
viral infection	1/24 (4.2%)	1
Nervous system disorders
headache	1/24 (4.2%)	1
Other (Not Including Serious) Adverse Events
	Alemtuzumab + Pentostatin
	Affected / at Risk (%)	# Events
Total	23/24 (95.8%)
Eye disorders
Ocular	2/24 (8.3%)	2
Gastrointestinal disorders
Nausea	15/24 (62.5%)	15
General disorders
Hives	9/24 (37.5%)	9
Edema	3/24 (12.5%)	3
fatugue	6/24 (25%)	6
Pain	7/24 (29.2%)	7
tumor lysis syndrome	2/24 (8.3%)	2
Hepatobiliary disorders
Hepatic	7/24 (29.2%)	7
Renal and urinary disorders
Renal	5/24 (20.8%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.