Ofatumumab With High Dose Methylprednisone Followed by Ofatumumab and Alemtuzumab in 17p CLL

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Dana-Farber Cancer Institute
Sponsor:
Collaborators:
National Comprehensive Cancer Network
GlaxoSmithKline
Information provided by (Responsible Party):
Jennifer R. Brown, MD, PhD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01465334
First received: October 18, 2011
Last updated: April 22, 2014
Last verified: April 2014
  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:


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 2014 (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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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: Caitlin Tesmer 617-632-6940 ctesmer1@partners.org

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Principal Investigator: Jon Arnason, MD         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Principal Investigator: Jennifer R Brown, 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: April 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
17p Deletion CLL

Additional relevant MeSH terms:
Alemtuzumab
Methylprednisolone
Methylprednisolone acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014