Campath-1H Plus Rituximab for CD52- and CD20- Positive Refractory or Relapsed Chronic Lymphoid Disorders

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00071396
• Collaborator: Bayer (Industry)
• Enrollment: 48
• Location: 1
• Arm: 1
• Duration (Months): 58
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to learn if giving CAMPATH-1H with rituximab can shrink or slow the growth of the disease in patients with chronic lymphoid disorders that have either not responded or whose disease has returned after treatment with standard therapies.

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia	Drug: Campath-1H; Drug: Rituximab	Phase 2

Detailed Description

Objectives:

1. To determine the efficacy and response rates of Campath-1H when given as a continuous intravenous infusion followed by subcutaneous injection plus rituximab in the treatment of chronic lymphoid disorders that are refractory to conventional therapy, have relapsed, or have no established frontline therapy.

2. To assess the safety of the combination of Campath-1H when given as a continuous intravenous infusion followed by subcutaneous injection plus rituximab in chronic lymphoid disorders that express both CD52 and CD20 cell surface antigens.

3. To measure levels of soluble (s) CD20 and sCD52 as well as levels of Campath-1H, rituximab and antibody complexes of rituximab/CD20 and Campath-1H/CD52 in patients with chronic lymphoid disorders treated with Campath-1H plus rituximab.

Study Design

• Study Type: Interventional
• Actual Enrollment: 48 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Continuous Infusion Followed by Subcutaneous Injection of Campath-1H Plus Rituximab in the Treatment of CD52- and CD20-Positive Refractory or Relapsed Chronic Lymphoid Disorders
• Study Start Date: Oct 1, 2002
• Actual Primary Completion Date: Sep 1, 2006
• Actual Study Completion Date: Aug 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Campath-1H + Rituximab Campath 15 mg/day continuous intravenous (IV) infusion x 6 days, then twice a week for 3 weeks as 30 mg injection under skin to complete 4 week treatment course. Rituximab 375 mg/m^2 IV infusion day 1, then 500 mg/m^2 on days 8, 15 + 22.	Drug: Campath-1H; 15 mg/day Continuous infusion by vein (IV) for 6 days then given twice a week for remaining three weeks as 30 mg injection under skin to complete one treatment course of 4 weeks.; Other Names: Alemtuzumab Campath ; Drug: Rituximab; 375 mg/m^2 IV infusion on day 1, then 500 mg/m^2 on days 8, 15, and 22.; Other Names: Rituxan

Outcome Measures

Primary Outcome Measures

1. Overall Response [After each 4 week course of treatment]

   Overall response categorized as 'Complete Remission,' 'Partial Remission,' or 'No Response.' Blood tests weekly while on active therapy, within 4-6 weeks following last dose of therapy, and every 3 to 6 (+/- month) thereafter as long as on study. Repeat bone marrow biopsy/aspirate with flow cytometry as applicable at the end of first course of therapy, (1 week) within 4-6 weeks following the last dose of therapy and every 6 to 12 months (+/-) thereafter as long as on study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age >/=15 years.

2. Written informed consent.

3. Patients with chronic lymphoid malignancies that are either refractory to frontline therapy or have relapsed and that have a predicted probability of response of less than 20% with conventional therapy or allogeneic/autologous stem cell transplantation.

4. The following histologies are included: B-cell chronic lymphocytic leukemia (B-CLL or B-cell CLL), B-cell prolymphocytic leukemia (PLL), chronic lymphoid leukemia (CLL/PLL), hairy cell leukemia and hairy cell variant, mantle cell leukemia/lymphoma, marginal zone lymphoma/leukemia, splenic lymphoma with villous lymphocytes, CLL with evidence of transformation (e.g., Richter's transformation), large granular lymphocytic leukemia (LGL and NK-cell type).

5. Patients with above mentioned histologies whose malignant cell population have expressed both CD52 and CD20 in >/= 20% of cells as assessed by flow cytometry or immunohistochemistry. Expression of CD20 or CD52 < 20% is permitted if patients received rituximab or alemtuzumab, respectively, within 3 months prior to study start.

Exclusion Criteria:

1. Patients who have previously received Rituximab and CAMPATH-1H in combination are excluded.

2. ECOG performance status of </= 2.

3. Serum creatinine </= 2mg/dL and total bilirubin of £ 2 mg/dL unless due to direct infiltration of the liver or kidney with malignant cells.

4. Patients with a past history of anaphylaxis following exposure to rat or mouse derived CDR-grafted humanized monoclonal antibodies are excluded <CDR = complementarity determining regions>.

5. Negative pregnancy test (serum or urine) if female and of childbearing potential only (non-childbearing is defined as greater than one year post-menopausal or surgically sterilized).

6. No prior chemotherapy, immunotherapy, or hormonal therapy within 2 weeks prior to study start. Hormonal replacement therapy is permitted. No prior therapy with monoclonal antibodies for at least 4 weeks prior to study start.

7. Patients at high risk of hepatitis B virus (HBV) infection and active HBV infection are excluded.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Bayer

Investigators

• Principal Investigator: Alessandra Ferrajoli, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• M.D. Anderson Cancer Center's website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00071396
• Other Study ID Numbers: ID02-368
• First Posted: Oct 22, 2003
• Last Update Posted: Aug 7, 2012
• Last Verified: Aug 1, 2012

• Keywords provided by M.D. Anderson Cancer Center: Chronic Lymphocytic Leukemia; CD-52 and CD-20 Positive; Refractory; Relapsed
• Additional relevant MeSH terms: Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Rituximab; Alemtuzumab

Study Results

Participant Flow

Recruitment Details	Recruitment Period 10/21/02 - 3/27/09; all patients were registered at the University of Texas MD Anderson Cancer Center.
Pre-assignment Detail	Of 48 patients enrolled, 41 patients were evaluable for response (2 patients withdrew before starting treatment and 2 were ineligible).

Arm/Group Title	Campath-1H + Rituximab
Arm/Group Description	Campath 15 mg/day continuous intravenous (IV) infusion for 6 days, then twice a week for 3 weeks as 30 mg injection under skin to complete 4 week treatment course. Rituximab 375 mg/m^2 IV infusion day 1, then 500 mg/m^2 on days 8, 15 + 22.
Period Title: Overall Study
STARTED	44
COMPLETED	41
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Campath-1H + Rituximab
Arm/Group Description	Campath 15 mg/day continuous intravenous (IV) infusion for 6 days, then twice a week for 3 weeks as 30 mg injection under skin to complete 4 week treatment course. Rituximab 375 mg/m^2 IV infusion day 1, then 500 mg/m^2 on days 8, 15 + 22.
Overall Participants	44
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	59
Sex: Female, Male (Count of Participants)
Female	9 20.5%
Male	35 79.5%
Region of Enrollment (participants) [Number]
United States	44 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response
Description	Overall response categorized as 'Complete Remission,' 'Partial Remission,' or 'No Response.' Blood tests weekly while on active therapy, within 4-6 weeks following last dose of therapy, and every 3 to 6 (+/- month) thereafter as long as on study. Repeat bone marrow biopsy/aspirate with flow cytometry as applicable at the end of first course of therapy, (1 week) within 4-6 weeks following the last dose of therapy and every 6 to 12 months (+/-) thereafter as long as on study.
Time Frame	After each 4 week course of treatment

Outcome Measure Data

Analysis Population Description

Analysis treated population 41 evaluable patients (44 treated, 3 not evaluable for response).

Arm/Group Title	Campath-1H + Rituximab
Arm/Group Description	Campath 15 mg/day continuous intravenous (IV) infusion for 6 days, then twice a week for 3 weeks as 30 mg injection under skin to complete 4 week treatment course. Rituximab 375 mg/m^2 IV infusion day 1, then 500 mg/m^2 on days 8, 15 + 22.
Measure Participants	41
Complete Remission	8 18.2%
Partial Remission	14 31.8%
No Response	19 43.2%

Adverse Events

Time Frame	3 years 11 months
Arm/Group Title	Campath-1H + Rituximab
Arm/Group Description	Campath 15 mg/day continuous intravenous (IV) infusion for 6 days, then twice a week for 3 weeks as 30 mg injection under skin to complete 4 week treatment course. Rituximab 375 mg/m^2 IV infusion day 1, then 500 mg/m^2 on days 8, 15 + 22.
All Cause Mortality
	Campath-1H + Rituximab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Campath-1H + Rituximab
	Affected / at Risk (%)	# Events
Total	8/44 (18.2%)
General disorders
Fever without neutropenia	1/44 (2.3%)	1
Fever	2/44 (4.5%)	2
Infections and infestations
Pneumonia	2/44 (4.5%)	2
Infection	3/44 (6.8%)	3
Febrile Neutropenia	3/44 (6.8%)	3
Other (Not Including Serious) Adverse Events
	Campath-1H + Rituximab
	Affected / at Risk (%)	# Events
Total	25/44 (56.8%)
Blood and lymphatic system disorders
Anemia	6/44 (13.6%)	6
Leukopenia	9/44 (20.5%)	12
Lymphopenia	7/44 (15.9%)	7
Thrombocytopenia	6/44 (13.6%)	6
Cardiac disorders
hypotension	5/44 (11.4%)	5
Gastrointestinal disorders
Nausea	8/44 (18.2%)	8
General disorders
Drug Fever	12/44 (27.3%)	13
fatigue	10/44 (22.7%)	10
febrile neutropenia	3/44 (6.8%)	3
fever	3/44 (6.8%)	5
Rigors Chills	18/44 (40.9%)	21
Infections and infestations
neutropenia	3/44 (6.8%)	5
Respiratory, thoracic and mediastinal disorders
dyspnea	4/44 (9.1%)	4
Skin and subcutaneous tissue disorders
puritis	7/44 (15.9%)	7
Injection site reaction	5/44 (11.4%)	8

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.