Clinical trial NCT03892421: Outpatient Administration of R-DHAP in Relapsed/Refractory Non-Hodgkin Lymphoma
Official title: Safety and Efficacy of an Outpatient Schedule of Rituximab, Cytarabine, Carboplatin, and Dexamethasone in Relapsed/Refractory Non-Hodgkin Lymphoma. Phase I/II Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Relapsed Non Hodgkin Lymphoma
Refractory Non-Hodgkin Lymphoma
Lead sponsor: La Raza Medical Center
Sponsor class: OTHER
First posted: 2019-03-27
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this study is to evaluate the efficacy and safety of a combination of the anti-CD20 monoclonal antibody Rituximab, Dexamethasone, daily high dose Cytarabine twice, and Carboplatin; delivered in an outpatient setting.

Detailed description: The R-DHAP (Rituximab, Dexamethasone, Cytarabine, and Cisplatin) schedule includes high-dose cytarabine every 12 hours and requires careful monitoring of renal toxicity because of cisplatin. These conditions limit the use of this protocol in an outpatient setting.

The S phase of lymphoma cells is longer than 12 hours, then cytarabine can be used daily without reduction of the antineoplastic effect. Carboplatin does not have remarkable renal toxicity so is not necessary to monitor blood chemistry or IV fluids during its administration.

The study hypothesis is that modifications to the original R-DHAP protocol, using cytarabine on a daily basis and the substitution of cisplatin by carboplatin can preserve the efficacy, reducing the incidence of renal events. The investigators hypothesize that those modifications can make the schedule more suitable for an outpatient administration in relapsed or refractory non-Hodgkin lymphoma patients.

After 3 cycles of chemotherapy, the overall response and the incidence of adverse events will be evaluated.

In order to achieve the purpose of this trial, 130 participants will be included.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of recurrent or refractory B-cell non-Hodgkin lymphoma
* Performance status: Eastern Cooperative Oncology Group 0-2
* At least three weeks from last chemotherapy
* Toxicities by Common Terminology Criteria Version 4.0 ≤ 1
* Glomerular filtration rate \>50 ml/min
* Women of childbearing potential must use effective methods of contraception

Exclusion Criteria:

* Post-transplant relapse of lymphoma
* Central nervous system involvement of lymphoma
* Serious infections
* Known allergies to one or more of the experimental drugs
* Diabetes with glucose \>200 mg/dl
* Pregnant or lactating females
* Known HIV or B Hepatitis positivity
* Known allergies to filgrastim

Primary outcomes:
measure: Overall Response Rate
timeFrame: 63 days
measure: Incidence of hematological toxicities > grade 2 by Common Terminology Criteria V4.0
timeFrame: 63 days
Secondary outcomes:
measure: Overall Survival
timeFrame: 12 months
measure: Progression Free Survival
timeFrame: 12 months
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: Hospital Especialidades Centro Medico La Raza
state: Azcapotzalco
Study officials:
affiliation: Hematology Department La Raza Medical Center
name: Study Officials H Caballero, MD Ms
role: PRINCIPAL_INVESTIGATOR
References:
citation: Velasquez WS, Cabanillas F, Salvador P, McLaughlin P, Fridrik M, Tucker S, Jagannath S, Hagemeister FB, Redman JR, Swan F, et al. Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP). Blood. 1988 Jan;71(1):117-22.
citation: Momparler RL. Optimization of cytarabine (ARA-C) therapy for acute myeloid leukemia. Exp Hematol Oncol. 2013 Aug 6;2:20. doi: 10.1186/2162-3619-2-20. eCollection 2013.
citation: Yanik G, Yousuf N, Miller MA, Swerdlow SH, Lampkin B, Raza A. In vivo determination of cell cycle kinetics of non-Hodgkin's lymphomas using iododeoxyuridine and bromodeoxyuridine. J Histochem Cytochem. 1992 May;40(5):723-8. doi: 10.1177/40.5.1573252.
citation: Sandlund JT, Santana VM, Hudson MM, Onciu M, Head D, Murry DJ, Ribeiro R, Wallace D, Rencher R, Pui CH. Combination of dexamethasone, high-dose cytarabine, and carboplatin is effective for advanced large-cell non-Hodgkin lymphoma of childhood. Cancer. 2008 Aug 15;113(4):782-90. doi: 10.1002/cncr.23630.