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

NCT01465334 | Terminated Phase 2 Results DMC

• 3 other identifiers: 11-304NCCN Protocol Number: NCCN-001GSK Protocol Number: OFT115580
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

CLL; SLL

Keywords

17p Deletion CLL

Outcome Measures

Primary Outcomes (1)

• Induction Overall Response Rate (ORR)

  Induction ORR is the percentage of participants achieving a minimum of partial response (PR) over induction treatment based on International Workshop on Chronic Lymphocytic Leukemia (IW-CLL) criteria (Hallek, et al 2008). There are numerous diagnostic tests used for response evaluation including potentially CBC and differential count, marrow aspirate and biopsy, ultrasound of the abdomen, CT scans (chest, pelvis, abdomen) and physical examination. PR is a 50% or greater decrease of measured size of lymphadenopathy, hepatomegaly, splenomegaly as well as blood lymphocytes (over baseline), marrow infiltrate or B-lymphoid nodules and a 50% or greater increase from baseline in platelet count (or level \>100,000/micro liter), hemoglobin (or level \>11 grams/deciliter), neutrophils (or level \>1500/microliter).

  Disease was evaluated after weeks 8 and 16 of Part A and at 12, 18 and 24 weeks during part B.

Secondary Outcomes (10)

• Number of Participants Achieving Induction Complete Response (CR)

  Disease was evaluated after weeks 8 and 16 of Part A and at 12, 18 and 24 weeks during part B.

• Overall Objective Response Rate (ORR)

  Disease was evaluated after weeks 8 and 16 of Part A, at 12, 18 and 24 weeks during part B and every 6 months on Part C.

• Number of Participants With Overall CR

  Disease was evaluated after weeks 8 and 16 of Part A, at 12, 18 and 24 weeks during part B and every 6 months on Part C.

• Overall MRD Negative Rate

  MRD was assessed after weeks 8 and 16 of Part A, at 12, 18 and 24 weeks during part B and every 6 months on Part C.

• Transplant Rate

  Evaluated up to 36 cycles (approximately 2.75 years) of treatment (Parts A, B and C)

Study Arms (2)

Treatment Naive

EXPERIMENTAL

Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28

Drug: Ofatumumab; Drug: High-Dose Methylprednisolone; Drug: Alemtuzumab

Relapsed/Refractory

EXPERIMENTAL

Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28

Drug: Ofatumumab; Drug: High-Dose Methylprednisolone; Drug: Alemtuzumab

Interventions

Ofatumumab DRUG

Also known as: GSK 1841157

Relapsed/Refractory; Treatment Naive

High-Dose Methylprednisolone DRUG

Also known as: HDMP

Relapsed/Refractory; Treatment Naive

Alemtuzumab DRUG

Also known as: Campath-1H

Relapsed/Refractory; Treatment Naive

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• National Comprehensive Cancer Network: collaborator
• GlaxoSmithKline: collaborator

Study Sites (2)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Davids MS, Kim HT, Yu L, De Maeyer G, McDonough M, Vartanov AR, Langey R, Fernandes SM, Hellman JM, Francoeur K, Arnason J, Jacobsen ED, LaCasce AS, Fisher DC, Brown JR. Ofatumumab plus high dose methylprednisolone followed by ofatumumab plus alemtuzumab to achieve maximal cytoreduction prior to allogeneic transplantation for 17p deleted or TP53 mutated chronic lymphocytic leukemia. Leuk Lymphoma. 2019 May;60(5):1312-1315. doi: 10.1080/10428194.2018.1519814. Epub 2018 Oct 15.

  PMID: 30322319 RESULT

MeSH Terms

Interventions

ofatumumab; Methylprednisolone; Alemtuzumab

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Jennifer R. Brown, MD, PhD
• Organization: Dana-Farber Cancer Institute

Jennifer_Brown@dfci.harvard.edu

(617) 632-3316

Study Officials

• Jennifer R Brown, MD PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 18, 2011
• First Posted: November 4, 2011
• Study Start: December 1, 2011
• Primary Completion: November 1, 2014
• Study Completion: January 1, 2017
• Last Updated: August 29, 2023
• Results First Posted: June 26, 2019

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)