DA-EPOCH-Rituximab/Metformin (RM) for Double Hit Lymphoma

NCT ID: NCT02815397

Last Updated: 2017-11-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2016-07-31

Brief Summary

Newly diagnosed histologically confirmed c-myc+ de novo DLBCL. Metformin 500 mg daily x 1 week, then 500 mg twice daily (BID) x 2 weeks, then 850 mg twice daily until 1 month after last cycle of chemo-immunotherapy.

DA-EPOCH-R every 21 days x 4 cycles (CNS prophylaxis single or triple therapy given intrathecally each cycle to patients deemed appropriate by treating physician).

Restage after 4 cycles with CT. Complete remission or partial remission: complete 2 more cycles or radiation therapy (XRT) consolidation per physician. Stable or progressive disease will go on to salvage therapy off study.

Detailed Description

Subject admitted to in-patient care for day 1 or each cycle and discharged on day 5. On day 6, subject receives Rituximab in outpatient infusion facility.

Metformin is dispensed on day 1 of each cycle and taken as follows: Cycle 1 days 1-7 500 mg daily. Days 8-21, 500 mg twice daily. Cycle 2 through end of treatment, metformin given 850 mg twice daily.

Inpatient treatment: DA-EPOCH every 21 days Etoposide (VP-16) 50 mg/m2/d civi d1-4 (continuous infusion) Prednisone 60 mg/m2 BID po d1-5 Vincristine 0.4 mg/m2/d civi d 1-4 (continuous infusion) Doxorubicin (Adriamycin) 10 mg/m2/d civi d1-4 (continuous infusion) Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 min d5 If clinically indicated, patients who are deemed appropriate for central nervous system (CNS) prophylaxis by their treating physician will receive either single agent intrathecal methotrexate (12 mg) or triple therapy (15 mg methotrexate, 30 mg cytarabine, 30 mg hydrocortisone) with each cycle of chemotherapy.

Rituximab 375 mg/m2 IV every 21 days on D6-8 post DA-EPOCH (per standard institutional guidelines) DA-dose adjustment paradigm based on twice weekly complete blood count (CBC) (dose adjustment above starting doses apply to Etoposide (VP-16), Doxorubicin (Adriamycin) and Cyclophosphamide (Cytoxan). If nadir absolute neutrophil count(ANC)>500/microliter (uL), 20% increase in all 3 drugs. If nadir<500/uL on 1 or 2 measurements, same doses as last cycle. If nadir <500/uL on at least 3 measurements, or nadir platelet <25,000/uL on 1 measurement, 20% decrease in Etoposide, Doxorubicin and Cyclophosphamide below last cycle.

Filgrastim (Neupogen) 5 mcg/kg sc qd beginning on d6 until ANC>5,000/uL or Pegfilgrastim (Neulasta) 6 mg sc 24-72 hours post chemotherapy.

Restaging with CT scans is done after cycle 4 and:

complete remission (CR)/partial remission (PR) - complete 2 more cycles of therapy OR consolidation radiation therapy per treating physician.

stable disease (SD)/progressive disease (PD) - salvage therapy off study.

Conditions

Diffuse Large B-Cell Lymphoma

Keywords

Double Hit DLBCL

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single arm, open label

Metformin added to standard of care treatment for all patients

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

given in addition to standard of care treatment

Interventions

Metformin

given in addition to standard of care treatment

Intervention Type: DRUG

Other Intervention Names

Glumetza, Fortamet, Glucophage, Riomet

Eligibility Criteria

Inclusion Criteria

• Male or female ≥ 18 years of age
• Diagnosis of DLBCL as documented by medical records and with histology based on criteria established by the World Health Organization

• subtyping is required for DLBCL
• c-myc+ defined as presence of c-myc breaks by karyotype/FISH and/or IHC ≥ 40%; this includes double hits (with bcl-2 breaks found using cytogenetics/FISH) and/or double expressors (with bcl-2 protein expression ≥ 70% by IHC); increased copy number in itself is not considered positivity for c-myc
• No prior therapy for diagnosis of DLBCL with exception of steroids
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0- 2 (Appendix B)
• Life expectancy of at least 6 months
• No history of medication dependent diabetes mellitus
• No evidence of acute or chronic metabolic acidosis (baseline venous lactate ≤ 4)

Exclusion Criteria

• Patient already on any class of anti-diabetic medication including metformin, insulin analogues, sulfonylureas, thiazolidinediones (TZDs) and the incretin-based therapies or clear need for therapeutic intervention based on fasting blood glucose
• Known histological transformation from indolent non-Hodgkin Lymphoma (iNHL) or chronic lymphocytic leukemia (CLL) to an aggressive form of non-Hodgkin's lymphoma (NHL) (ie, Richter transformation)
• Burkitt and/or precursor lymphoblastic leukemia/lymphoma.
• Presence of known intermediate- or high-grade myelodysplastic syndrome
• History of an active of treated non-lymphoid malignancy within the last 3 years excluding basal cell and squamous cell skin cancers
• Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of start of study drug.
• Subjects who have currently active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver involvement with NHL or stable chronic liver disease per investigator assessment)
• Renal insufficiency with creatinine > 1.5 x upper limit of normal (ULN) OR creatinine clearance of < 45 ml/min as calculated by the Cockcroft-Gault method
• CNS or leptomeningeal involvement of lymphoma
• HIV positive
• Ongoing inflammatory bowel disease
• Ongoing alcohol or drug addiction
• Pregnancy or breastfeeding
• History of prior allogeneic bone marrow progenitor cell or solid organ transplantation -

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Elsa U. Pardee Foundation

OTHER

Sponsor Role: collaborator

Rush University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Reem Karmali, MD

Role: PRINCIPAL_INVESTIGATOR

Rush Medical Center

Locations

Rush University Medical Center

Chicago, Illinois, United States

Countries

United States

Other Identifiers

LYM15 DA-EPOCH-RM

Identifier Type: -

Identifier Source: org_study_id