Ofatumumab With High Dose Methylprednisone Followed by Ofatumumab and Alemtuzumab in 17p CLL - Full Text View

Purpose

The main purpose of this study is to examine how two separate groups of 17p deletion Chronic lymphocytic leukemia (CLL) participants respond to sequential treatment with this particular combination of drugs. The two groups are those participants who have previously received treatment for their CLL and those who have not yet received any treatment. The combination of drugs is Ofatumumab and High-Dose Methylprednisolone (HDMP) first followed by Ofatumumab and Alemtuzumab. All three drugs are FDA approved and have known activity in treating 17p CLL. We hope that by combining these drugs together in this study, they will have more benefit than each one alone and that the subjects' CLL will be significantly impacted.

Condition	Intervention	Phase
CLL SLL	Drug: Ofatumumab Drug: High-Dose Methylprednisolone Drug: Alemtuzumab	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase II Study of Ofatumumab-High Dose Methylprednisolone Followed by Ofatumumab-Alemtuzumab in 17p Deletion CLL

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Prednisolone Prednisolone acetate Methylprednisolone acetate Methylprednisolone Prednisolone sodium phosphate Prednisolone phosphate Prednisolone sodium succinate Methylprednisolone sodium succinate Alemtuzumab Ofatumumab

U.S. FDA Resources

Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:

Overall Response Rate (ORR) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
To determine the ORR at the conclusion of two-part induction therapy with ofatumumab-HDMP (Part A) followed by ofatumumab-alemtuzumab (Part B) in two cohorts of participants with 17p deletion: previously untreated, or relapsed/refractory.

Secondary Outcome Measures:

Complete response (CR) Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
To determine the CR rate, rate of objective response by disease compartment (nodes/spleen, cytopenias/bone marrow) rate of MRD negativity by four color flow cytometry, PFS and OS for induction therapy with ofatumumab-HDMP followed by ofatumumab-alemtuzumab in each cohort.
ORR, CR Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
To determine the ORR, CR rate, rate of objective response by disease compartment (nodes/spleen, cytopenias/bone marrow) and rate of Minimal Residual Disease (MRD) negativity at the conclusion of ofatumumab-HDMP; and at earlier interim analysis after two cycles of ofatumumab-HDMP. To determine the number of participants eligible to stop ofatumumab-HDMP after two cycles, as well as the number who complete two versus four cycles.
Improvement in ORR, CR rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
To determine the improvement in ORR, CR rate and the rate at which MRD negativity is achieved in bone marrow with ofatumumab-alemtuzumab, following initial HDMP-ofatumumab.
Improvement in ORR, CR Rate during maintenance [ Time Frame: 2 years ] [ Designated as safety issue: No ]
To determine the improvement in ORR, CR rate and rate of MRD negativity, as well as the rate of detectable recurrence of MRD or frank relapse, during maintenance ofatumumab-alemtuzumab in those participants not eligible for or willing to undergo allogeneic SCT.
Rate of subjects proceeding to transplant [ Time Frame: 2 years ] [ Designated as safety issue: No ]
To determine the rate at which transplant-eligible participants are able (and willing) to proceed to allogeneic SCT for consolidation of remission.
Safety [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
To assess the safety of ofatumumab-HDMP followed by ofatumumab-alemtuzumab in each cohort, and the safety of ofatumumab-alemtuzumab consolidation. All participants receiving investigational agents will be evaluated for safety. The safety parameters include all laboratory tests and hematological abnormalities, physical examination findings, and spontaneous reports of adverse events and serious adverse events reported to the investigator by participants. All toxicities encountered during the study will be evaluated according to the NCI criteria and recorded prior to each course of therapy.

Estimated Enrollment:	54
Study Start Date:	November 2011
Estimated Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Previously Treated Subjects with 17p deletion CLL who have received prior treatment	Drug: Ofatumumab 1000 mg IV Drug: High-Dose Methylprednisolone 1000 mg/m2 IV Other Name: HDMP Drug: Alemtuzumab 30 mg subcutaneously Other Name: Campath-1H
Active Comparator: Treatment Naive Subjects with 17p deletion CLL with no prior treatment	Drug: Ofatumumab 1000 mg IV Drug: High-Dose Methylprednisolone 1000 mg/m2 IV Other Name: HDMP Drug: Alemtuzumab 30 mg subcutaneously Other Name: Campath-1H

Detailed Description:

There are three possible components to the treatment in this study:

Part A - Ofatumumab + HDMP

A maximum of 4 cycles of 28 days. Ofatumumab and HDMP will be given intravenously. Ofatumumab will given on days 1, 8, 15 and 22. HDMP will given on days 1, 2, and 3.

Part B - Ofatumumab + Alemtuzumab

Subjects who have not experienced a Complete Response with no residual detectable disease after Part A will continue on to Part B.
A maximum of 6 cycles of 28 days. Ofatumumab will be given intravenously on day 1 and Alemtuzumab will be given as a subcutaneous (under the skin) injection on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26.

Part C - Maintenance with Ofatumumab + Alemtuzumab

Subjects who have experienced at least stable disease in Parts A and B can continue on to Part C. Subjects who are eligible may instead proceed to stem cell transplantation after Parts A and B.
Part C is a maximum of 26 cycles of 28 days. Ofatumumab will be given intravenously every other cycle. Alemtuzumab will be given as a subcutaneous injection every 14 days.

During all cycles subjects will also have clinical exams, and blood tests; imaging tests (CT scans), bone marrow aspirate and biopsy, and serum pregnancy tests (if applicable) will occur at various intervals.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Documented CLL/SLL
17p deletion by FISH in 20% or more nuclei on peripheral blood, bone marrow or lymph node
Normal organ function

Exclusion Criteria:

Pregnant or breast feeding
Current active hepatic or biliary disease
Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, tuberculosis and active Hepatitis C
History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae
Other past or current malignancy. Participants who have been free of malignancy for at least 2 years, or who have a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
Known HIV positive
Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months prior to study entry, congestive heart failure, and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities.
Significant concurrent uncontrolled medical conditions including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the subject.
Positive serology for Hepatitis B or C
History of allergic reactions attributed to ofatumumab.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01465334

Contacts

Contact: Jennifer R Brown, MD PhD	617-632-4564	jennifer_brown@dfci.harvard.edu
Contact: Alexander R Vartanov	617-582-8363	AlexanderR_Vartanov@dfci.harvard.edu

Locations

United States, Massachusetts
Dana-Farber Cancer Institute	Recruiting
Boston, Massachusetts, United States, 02215
Principal Investigator: Jennifer R Brown, MD
Beth Israel Deaconess Medical Center	Recruiting
Boston, Massachusetts, United States, 02215
Principal Investigator: Jon Arnason, MD

Sponsors and Collaborators

Dana-Farber Cancer Institute

National Comprehensive Cancer Network

GlaxoSmithKline

Investigators

Principal Investigator:

Jennifer R Brown, MD PhD

Dana-Farber Cancer Institute

More Information

No publications provided

Responsible Party:	Jennifer R. Brown, MD, PhD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT01465334 History of Changes
Other Study ID Numbers:	11-304, NCCN Protocol Number: NCCN-001, GSK Protocol Number: OFT115580
Study First Received:	October 18, 2011
Last Updated:	February 20, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:

17p Deletion CLL

Additional relevant MeSH terms:

Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Alemtuzumab
Campath 1G
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents

Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on May 23, 2013