Clinical Trials /

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

NCT01465334

Description:

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.

Related Conditions:
  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title:Ofatumumab With High Dose Methylprednisone Followed by Ofatumumab and Alemtuzumab in 17p CLL
  • Official Title:A Phase II Study of Ofatumumab-High Dose Methylprednisolone Followed by Ofatumumab-Alemtuzumab in 17p Deletion CLL

Clinical Trial IDs

  • ORG STUDY ID: 11-304
  • SECONDARY ID: NCCN Protocol Number: NCCN-001
  • SECONDARY ID: GSK Protocol Number: OFT115580
  • NCT ID: NCT01465334

Trial Conditions

  • CLL
  • SLL

Trial Interventions

DrugSynonymsArms
OfatumumabPreviously Treated
High-Dose MethylprednisoloneHDMPPreviously Treated
AlemtuzumabCampath-1HPreviously Treated

Trial 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.

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.

Trial Arms

NameTypeDescriptionInterventions
Previously TreatedActive ComparatorSubjects with 17p deletion CLL who have received prior treatment
  • Ofatumumab
  • High-Dose Methylprednisolone
  • Alemtuzumab
Treatment NaiveActive ComparatorSubjects with 17p deletion CLL with no prior treatment
  • Ofatumumab
  • High-Dose Methylprednisolone
  • Alemtuzumab

Eligibility 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.

Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Both
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:2 years
Safety Issue:No
Description: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

Measure:Complete response (CR) Rate
Time Frame:2 years
Safety Issue:No
Description: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.
Measure:ORR, CR Rate
Time Frame:2 years
Safety Issue:No
Description: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.
Measure:Improvement in ORR, CR rate
Time Frame:2 years
Safety Issue:No
Description: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.
Measure:Improvement in ORR, CR Rate during maintenance
Time Frame:2 years
Safety Issue:No
Description: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.
Measure:Rate of subjects proceeding to transplant
Time Frame:2 years
Safety Issue:No
Description:To determine the rate at which transplant-eligible participants are able (and willing) to proceed to allogeneic SCT for consolidation of remission.
Measure:Safety
Time Frame:2 years
Safety Issue:Yes
Description: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.

Trial Keywords

  • 17p Deletion CLL