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Diffuse Large B-cell Lymphoma (DLBCL)Phase 1/2R²-DHAPNCT02983097

Therapy of Non-Hodgkin-Lymphoma by Combination of Lenalidomide + Rituximab, Dexa, High-dose ARA-C and CisP

A Phase 1/2 study testing Rituximab, Cisplatin and Carboplatin in people with Diffuse Large B-cell Lymphoma (DLBCL) and Follicular Lymphoma Grade III (FL III°), run by Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbH at 12 sites in Germany.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The goal of this study is to evaluate efficacy and safety of the combination of lenalidomide, an immunomodulatory drug (IMiD) with a standard immunochemotherapy treatment, called R-DHAP. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Rituximab, Cisplatin and Carboplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
12 sitesGermany
Study dates
Nov 2010to 28 Apr 2015
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age: 18-70
  • Risk groups: All risk groups
  • histology: diagnosis or a recurrent or primary progressive aggressive b-cell non-hodgkin lymphoma, in particular
  • follicular lymphoma grade III
  • diffuse large b-cell lymphoma
  • burkitt lymphoma
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  • mantle cell lymphoma, blastoid variant
  • aggressive marginal zone lymphoma
  • Performance status: ECOG 0-2
  • Criteria for women of childbearing potential:
  • Women of childbearing potential have to:
  • understand the teratogenic risk associated with the study therapy, especially lenalidomide
  • understand the need of reliable, uninterrupted birth control from 4 weeks prior to the start of the study drug, during the duration of the study treatment, and 4 weeks after completion of study treatment, and be able to reliably use birth control, except if the patient commits to absolute sexual abstinence, confirmed on a monthly basis
  • The following are effective methods of contraception:
  • implant
  • levonorgestrel-releasing intrauterine system (IUS)
  • medroxyprogesterone acetate depot
  • tubal sterilisation
  • sexual intercourse with a vasectomised male partner only, vasectomy must be confirmed by two negative semen analyses
  • ovulation-inhibitory progesterone-only pills If not established on effective contraception, the female subject must be referred to an appropriately trained health care professional for contraceptive advice in order that contraception can be initiated.
  • Understand that even if she has amenorrhea, she must follow all the advice on effective contraception
  • Understand the potential consequences of pregnancy and the need to rapidly consult if there is a risk of pregnancy.
  • Agree to have a medically supervised pregnancy test with a minimum sensitivity of 25 mIU/ml on the day of the study visit or in the 3 days prior to the study visit once the subject has been on effective contraception for at least 4 weeks. This requirement also applies to women of childbearing potential who practice complete and continued abstinence. The test should ensure the subject is not pregnant when she starts treatment.
  • Agree to have a medically supervised pregnancy test every 4 weeks including 4 weeks after the end of study treatment, except in the case of confirmed tubal sterilization. These pregnancy tests should be performed on the day of the study visit or in the 3 days prior to the study visit. This requirement also applies to women of childbearing potential who practice complete and continued abstinence.
  • Male patients have to:
  • Agree to use condoms throughout study drug therapy, during any dose interruption and for one week after cessation of study therapy if their partner is of childbearing potential and has no contraception.
  • Agree not to donate semen during study drug therapy and for one week after end of study drug therapy.
  • All patients have to:
  • Agree to abstain from donating blood while taking study drug therapy and for one week following discontinuation of study drug therapy.
  • Agree not to share study medication with another person and to return all unused study drug to the investigator
  • Patients must be able to take low molecular weight heparin as prophylactic anticoagulation
  • Written informed consent is necessary

Who cannot join

  • pregnant or lactating females
  • already initiated salvage lymphoma therapy (except prephase as specified in this study)
  • serious accompanying disorder or impaired organ function causing significant clinical problems and reduced lyfe expectancy, in particular: heart: angina pectoris CCS>2 cardiac failure NYHA>2 and/or EF<45% lungs: FeV1<60%, diffusion capacity <50% of the reference values kidneys: creatinine>2 times the upper reference limit liver: bilirubin >2 times the upper reference limit
  • platelets <80000/mm³, leukocytes <2500/³
  • CNS involvement of lymphoma
  • known hypersensitivity to the medications to be used
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  • known HIV-positivity
  • suspicion that patient compliance will be poor, especially that rules for effective contraception will not be followed
  • simultaneous participation in other treatment studies
  • non-conformity to eligibility criteria

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

Germany12 sites

  • Diakonie Krankenhaus Bremen

    Bremen, 28239

  • Klinikum Chemnitz

    Chemnitz, 09113

  • Universitätsklinikum Essen

    Essen, 45122

  • Klinikum Frankfurt/Oder

    Frankfurt (Oder), 15236

  • Universitätsklinikum Göttingen

    Göttingen, 37075

  • Asklepios Klinik St. Georg

    Hamburg, 20099

  • Asklepios Klinik Altona

    Hamburg, 22763

  • Universitätsklinikum Heidelberg

    Heidelberg, 69120

  • Universitätsklinikum des Saarlandes

    Homburg, 66421

  • Westpfalz Klinikum

    Kaiserslautern, 67665

  • Städtisches Klinikum Karlsruhe

    Karlsruhe, 76133

  • LMU Klinikum München-Großhadern

    München, 81377

Other trials in Germany

About this study

Official title: Open-label, Multicenter Phase I/II Study: Salvage Therapy of Progressive and Relapsed Aggressive Non-Hodgkin-Lymphoma by Combination of Lenalidomide (Revlimid®) With Rituximab, Dexamethason, High-dose ARA-C and Cisplatinum (R²-DHAP)

The goal of this study is to evaluate efficacy and safety of the combination of lenalidomide, an immunomodulatory drug (IMiD) with a standard immunochemotherapy treatment, called R-DHAP. R-DHAP consists of a monoclonal antibody called Rituximab and chemotherapy consisting of Dexamethasone, high dose Cytarabine, often called Ara-C, and platinum based chemotherapy, either cisplatinum, or, if treatment with cisplatinum is contraindicated, carboplatinum.

Read the detailed description

This is a phase 1/2 study to evaluate the efficacy and safety of lenalidomide added to a standard chemotherapy regime of R-DHAP (Rituximab, Dexamethasone, high-dose Cytarabine, Cis/Carboplatinum) in the treatment of relapsed or refractory high-grade B-cell non-hodgkin-lymphoma (NHL).

The study hypothesis is that the combination of lenalidomide with standard immunochemotherapy will lead to an overall response rate of at least 60%. In this study, 3 rounds of immunochemotherapy in combination with lenalidomide will be administered. After the first or second round of therapy, peripheral hematopoetic stem cells will be harvested. Consolidation treatment with autologous or allogenic peripheral blood stem cell transplantation is recommended in all patients suitable, but is not part of the study.

In phase 1, up to six cohorts of at least 6 patients each will be treated with the study therapy, with lenalidomide in increasing dosages, to determine the maximum tolerated dose (MTD).

In phase 2, 50 patients will be treated with the MTD. Efficacy and safety will be evaluated.

Keywords
lymphoma, relapse, recurrence, progress, progressive, b-cell lymphoma, chemotherapy, immunotherapy, IMiD, Salvage chemotherapy, peripheral stem cell mobilization, lenalidomide, Rituximab, CD20, Cytarabine, Ara-C, platinum-based chemotherapy, Cisplatin, Carboplatin, Cisplatinum
Medical subject headings
Lymphoma, Large B-Cell, Diffuse, Lymphoma, Mantle-Cell, Burkitt Lymphoma, Lymphoma, Recurrence, Lymphoma, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RituximabDrug

    Also called MabThera

    Rituximab 375 mg/m²

  • CisplatinDrug

    Also called Cisplatinum

    Cisplatinum 100 mg / m²

  • CarboplatinDrug

    Also called Carboplatinum

    Carboplatinum AUC5

  • DexamethasoneDrug

    Dexamethasone 40 mg

  • CytarabineDrug

    Also called Cytarabin, Ara-C

    Cytarabine 2000 mg/m², administered twice

  • LenalidomideDrug

    Also called Revlimid

    5-20 mg administered either d1-d7, or d-6-d7

  • PegFilgrastimDrug

    Also called Neulasta

    PegFilgrastim 6 mg

  • peripheral stem cell collectionProcedure or surgery

    Also called peripheral stem cell apheresis, hematopoetic stem cell apheresis, peripheral hematopoetic stem cell apheresis

    collection of peripheral stem cells for autologous stem cell transplantation

Study groups in NCT02983097
Study groupRoleWhat they receive
R²-DHAPExperimentalCombination treatment with immunochemotherapy (R-DHAP) and lenalidomide Dosage: Rituximab 375 mg/m² day 1, i.v. Cisplatin 100 mg/m² or Carboplatin AUC5 day 2, i.v. Cytarabine 2000 mg/m², administered twice, on day 3, i.v. Dexamethasone 40 mg, days 2-5, p.o. Lenalidomide 5-20 mg, day 1-7 / day-6-+7, p.o. PEG-Filgrastim 6 mg, day 6, s.c. peripheral stem cell collection after cycle 1 or 2
Receives: Drug: Rituximab; Drug: Cisplatin; Drug: Carboplatin; Drug: Dexamethasone; Drug: Cytarabine; Drug: Lenalidomide; Drug: PegFilgrastim; Procedure: peripheral stem cell collection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rate (ORR)

    The percentage of patients which showed either a partial remission (PR), a complete remission with remaining uncertainty (CRu) or a complete remission (CR) after study treatment.

    Measured: 78 - 85 days + 2 years Follow Up

  2. Maximum tolerated dose (MTD)

    The maximum dose of lenalidomide tolerated with acceptable toxicity during phase 1 of this study. The MTD established in phase 1 of this study will be administered to 50 patients in phase 2 of this study.

    Measured: 78 - 85 days

Secondary outcomes (10)

  1. Rate of complete remission

    laboratory, BM biopsy, imaging

    Measured: 78 - 85 days + 2 years Follow Up

  2. Rate of primary progression

    The rate of patients which show progressive disease (PD) during or directly after study therapy

    Measured: 78 - 85 days + 2 years Follow Up

  3. Rate of treatment related deaths

    check survival

    Measured: 78 - 85 days + 2 years Follow Up

  4. Relapse Rate

    laboratory, BM biopsy, imaging

    Measured: 78 - 85 days + 2 years Follow Up

  5. Overall Survival

    check survival

    Measured: 78 - 85 days + 2 years Follow Up

  6. Progression free survival

    laboratory, BM biopsy, imaging

    Measured: 78 - 85 days + 2 years Follow Up

  7. tumour control

    laboratory, BM biopsy

    Measured: 78 - 85 days + 2 years Follow Up

  8. feasibility of stem cell mobilization

    The collection of peripheral stem cells is needed to be able to offer the patient high dose chemotherapy followed by autologous stem cell transplantation after the study treatment has ended.

    Stem cell collection of <2.0 *10e6 CD34+cells/kg will be considered insufficient.

    Measured: 78 - 85 days + 2 years Follow Up

  9. incidence of non-hematological toxicities > grade 2 CTC

    Measured: 78 - 85 days + 2 years Follow Up

  10. incidence and duration of neutropenia and thrombopenia grade 4

    laboratory WBC < 1.0 /nl or Plt < 25 /nl

    Measured: 78 - 85 days + 2 years Follow Up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Dec 2016 (estimated)
  2. Study startNov 2010
  3. Primary completionJan 2014
  4. Study completion28 Apr 2015

Why it stopped: Phase II: no scientific interests are given anymore

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02983097
Sponsor's protocol ID
DSHNHL 2008 R6
Other IDs
2009-010824-25, 2009
Acronym
R²-DHAP
Status last verified
Dec 2016
First submitted
14 Nov 2013
Last updated
19 Jan 2018
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Rituximab, Cisplatin and Carboplatin in people with Diffuse Large B-cell Lymphoma (DLBCL) and Follicular Lymphoma Grade III (FL III°), run by Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbH at 12 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Phase II: no scientific interests are given anymore). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) (time frame: 78 - 85 days + 2 years Follow Up). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02983097.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2018.

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