Multiple MyelomaPhase 1/2NCT01303965

Allo Transplant Followed by Lenalidomide and Sirolimus Maintenance in High-Risk Multiple Myeloma (MM)

A Phase 1/2 study testing Sirolimus, Tacrolimus and Lenalidomide in people with Multiple Myeloma, run by Sherif S. Farag at 1 site in United States.

Terminated

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

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Multiple Myeloma
What is being tested?: Sirolimus, Tacrolimus and Lenalidomide
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 14 participants
Where: 1 siteUnited States
Study dates: 7 Feb 2011to 28 Jul 2017
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Recipient Inclusion Criteria:

1. Understand and voluntarily sign an informed consent form.
2. Age 18-70 years at the time of signing the informed consent form.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Previously documented multiple myeloma (MM) with measurable monoclonal protein by either serum/urine protein electrophoresis or serum free light chains, or measurable plasmacytomas.
5. ECOG performance status of 0-2 at study entry (see Appendix 2).
6. Acceptable organ function as outlined in the protocol.
7. Otherwise fitting institutional criteria for allogeneic stem cell transplantation.
8. Presence of an HLA-matched (5/6 or 6/6 matched for HLA-A, B, and DR) sibling donor, or a HLA-matched (matched for at least HLA-A, B, C, and DRB1) unrelated donor by high-resolution testing.
9. Disease free of prior malignancies for >/= 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix or breast.
10. All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
11. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test

Recipient Exclusion Criteria:

1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
2. Pregnant or breast feeding females.
3. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
4. Known hypersensitivity to thalidomide or Lenalidomide.
5. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
6. Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine or prior infection to which they are now immune (i.e., not carriers) are eligible.

Donor Inclusion Criteria:

The following categories of donor will be acceptable:

1. HLA-matched related donor (5/6 or 6/6 match): Minimal typing necessary is serologic typing for class I (A, B) and molecular typing for class II (DRB1).
2. HLA-matched Unrelated Donor (MUD): Molecular identity at least at HLA A, B, C, and DRB1 and DQB1 (8/10 match) by high resolution typing is required.
3. Syngeneic donors are not eligible.
4. The donor must be healthy and must be an acceptable donor as per institutional standards for marrow or stem cell donation.
5. Age ≥ 18 years

Trial locations and contacts

1 site in 1 country.

United States1 site

Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202

Other trials in United States

About this study

Official title: Phase I/II Trial of Allogeneic Peripheral Blood Stem Cell Transplantation Followed by Maintenance Therapy With Lenalidomide and Sirolimus in Patients With High-Risk Multiple Myeloma

One of the complications that can occur after a stem cell transplant is called graft versus host disease (GVHD). Another complication is that multiple myeloma may come back (relapse). In this study, a drug called lenalidomide will be started 1-2 months after a transplant, or possibly later depending on recovery of your side effects. Lenalidomide and sirolimus have been shown to work together against multiple myeloma. Therefore, lenalidomide will be combined with sirolimus with the hope that this will help prolong the amount of time the disease is in remission. Researchers hope these steps will help prolong the amount of time the multiple myeloma is in remission and will decrease the chance of GvHD.

Conditions: Multiple Myeloma
Being tested: Sirolimus, Tacrolimus, Lenalidomide
Medical subject headings: Multiple Myeloma

What participants receive

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

SirolimusDrug
Start on Day -3 and continue for 1 year
TacrolimusDrug
Start on Day -3 and begin tapering on Day +100 until Day +180.
LenalidomideDrug
Start between Day +30 and +120 and continue for 1 year.

Study groups in NCT01303965
Study group	Role	What they receive
Open Label, Single Arm	Experimental	Use sirolimus and tacrolimus as GvHD prophylaxis with sirolimus and lenalidomide as post-transplant maintenance Receives: Drug: Sirolimus; Drug: Tacrolimus; Drug: Lenalidomide

What is being measured

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

Phase I: Number of Participants With Dose Limiting Toxicity
The number of patients who had a DLT during the dose finding/confirming portion (Phase I) of the trial for the safety of the combination of sirolimus, tacrolimus and lenalidomid. Patients will be monitored for 28 days (a cycle) to determine whether a DLT is experienced for the specific dose level.
Measured: 28 days
Phase II: Percent of Patients Alive and Free of Progression at 12 Months Following Transplant
Percent of patients and the 95% Binomial Confidence interval who were alive and free of progression at 12 months following transplant for the patients in Phase II. Progression will be based on International Myeloma Working Group criteria where patients may meet any one of the following criteria - increase of 25% or more in serum or urine M-protein from baseline, Serum M-protein and/or the absolute increase must be >=0.5 g/dl, Urine M-protein and/or absolute increase must be >=200 mg/24 hours, development of new bone lesions or soft tissue plasmacyomas or definite increase in the size of existing bone lesions or soft tissue plasmacyomas, or development of hypercalcemia (corrected serum Ca++>11.5 mg/dl) that can be attributed solely to plasma cell proliferative disease.
Measured: Transplant (Day 0) through 1 year post-transplant

Secondary outcomes (6)

Phase II - Percent of Patients With Acute Graft Versus Host Disease (GvHD)
Percent of patients and the 95% Binomial Confidence interval who had any stage I-IV acute GvHD based on the modified Keystone Grading Scale for skin, liver and gastrointestinal symptoms for patients in Phase II. Zero means no acute GvHD was reported, and higher stages are worse outcomes (range of 0-4).
For skin: 0=no rash; 1=erthematous macular rash over <25% body surface; 2=over 25-50% of body surface; 4=bullae, exfoliation ulcerative dermatitis.
For liver (bilirubin (mg/dL)): 0= <2.0; 1= 2-<2.9; 3= 3-<5.9; 4= >=15 . For gut changes (diarrhea[ml/day]): 0=none; 1= >500-1000; 2= >1000-1500; 3= >1500; 4=severe abdominal pain with or without ileus.
Overall grade 0: Skin=0; liver=0; gut changes=0. Overall grade 1: Skin with 1 or 2; liver=0; gut changes=0. Overall grade 2: Skin with 1, 2, or 3; liver=1; gut changes=1. Overall grade 3: Skin with 2 or 3; liver with 2 or 3; gut changes with 2 or 3. Overall grade 4: Patients with grade 4 toxicity in any organ system.
Measured: Day 0 through 1 year post transplantation
Phase II - Percent of Patients With Chronic Graft Versus Host Disease (GvHD)
Percent of patients and the 95% Binomial Confidence interval who had any chronic GvHD reported based on Filipovich et al. consensus document (BB\&MT 2005) and Akpek et al. chronic GvHD grading system (Blood 2003) for patients in Phase II.
Measured: Transplant (Day 0) through 1 year post-transplant
Phase II - Percent of Patients With Treatment-related Deaths at 100 Days
Percent of patients and the 95% Binomial Confidence interval who had treatment-related deaths by 100 days for patients in Phase II.
Measured: 100 days post transplant
Phase II - Percent of Patients With Treatment-related Deaths at 1 Year
Percent of patients and the 95% Binomial Confidence interval who had treatment-related deaths by 1 year for patients in Phase II.
Measured: Transplant (Day 0) through 1 year post-transplant
Phase II - Time to Neutrophil Engraftment
Time to neutrophil engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of neutrophils is defined as the time from day 0 to the date of the first of three consecutive days after transplantation during which the absolute neutrophils count (ANC) is at least 0.5 x109/l. Patients surviving at least 14 days after transplant will be evaluable for this endpoint. Patients who did not have neutrophil engraftment before death will be censored at the date of death. The median and 95% confidence intervals will be provided.
Measured: Transplant (Day 0) through 1 year post transplant
Phase II - Time to Platelet Engraftment
Time to platelet engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of platelets is defined as the time from day 0 to the first of three consecutive Complete Blood Counts (CBCs) obtained on different days after transplantation during which the platelet count is at least 20 x109/l. The CBCs obtained should be at least seven days after the most recent platelet transfusion. Only patients who achieved engraftment of platelets will be included in the analysis. The median and 95% confidence intervals will be provided.
Measured: Transplant (Day 0) through 1 year post-transplant

Timeline

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

7 Feb 201128 Jul 2017

First posted25 Feb 2011 (estimated)
Study start7 Feb 2011
Primary completion23 Sep 2014
Study completion28 Jul 2017

Why it stopped: Slow accrual

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Multiple MyelomaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: 14 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01303965
Sponsor's protocol ID: 1012-24; IUCRO-0307
Status last verified: Dec 2018
First submitted: 18 Feb 2011
Last updated: 8 Jan 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Active, not recruitingPhase 3
A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)
Multiple Myeloma
Active, not recruitingPhase 1/2
A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment
Multiple Myeloma
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm

All Multiple Myeloma trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I/II Trial of Allogeneic Peripheral Blood Stem Cell Transplantation Followed by Maintenance Therapy With Lenalidomide and Sirolimus in Patients With High-Risk Multiple Myeloma
ClinicalTrials.gov ID: NCT01303965
Acronym / sponsor ID: 1012-24; IUCRO-0307
Conditions: Multiple Myeloma
Phase: Phase 1/2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Slow accrual
Enrolment: 14 participants (actual)
Lead sponsor: Sherif S. FaragUniversity, hospital or other
Collaborators: Celgene Corporation
Study start: 7 Feb 2011 (actual)
Primary completion: 23 Sep 2014 (actual)
Study completion: 28 Jul 2017 (actual)
First posted: 25 Feb 2011 (estimated)
Results: Posted 6 Dec 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Open Label, Single Arm	Experimental	Drug: Sirolimus, Drug: Tacrolimus, Drug: LenalidomideUse sirolimus and tacrolimus as GvHD prophylaxis with sirolimus and lenalidomide as post-transplant maintenance

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
SirolimusStart on Day -3 and continue for 1 year	Drug	Open Label, Single Arm
TacrolimusStart on Day -3 and begin tapering on Day +100 until Day +180.	Drug	Open Label, Single Arm
LenalidomideStart between Day +30 and +120 and continue for 1 year.	Drug	Open Label, Single Arm

Primary outcome

Phase I: Number of Participants With Dose Limiting Toxicity
Time frame: 28 days
The number of patients who had a DLT during the dose finding/confirming portion (Phase I) of the trial for the safety of the combination of sirolimus, tacrolimus and lenalidomid. Patients will be monitored for 28 days (a cycle) to determine whether a DLT is experienced for the specific dose level.
Phase II: Percent of Patients Alive and Free of Progression at 12 Months Following Transplant
Time frame: Transplant (Day 0) through 1 year post-transplant
Percent of patients and the 95% Binomial Confidence interval who were alive and free of progression at 12 months following transplant for the patients in Phase II. Progression will be based on International Myeloma Working Group criteria where patients may meet any one of the following criteria - increase of 25% or more in serum or urine M-protein from baseline, Serum M-protein and/or the absolute increase must be >=0.5 g/dl, Urine M-protein and/or absolute increase must be >=200 mg/24 hours, development of new bone lesions or soft tissue plasmacyomas or definite increase in the size of existing bone lesions or soft tissue plasmacyomas, or development of hypercalcemia (corrected serum Ca++>11.5 mg/dl) that can be attributed solely to plasma cell proliferative disease.

6 secondary outcomes

Phase II - Percent of Patients With Acute Graft Versus Host Disease (GvHD)
Time frame: Day 0 through 1 year post transplantation
Phase II - Percent of Patients With Chronic Graft Versus Host Disease (GvHD)
Time frame: Transplant (Day 0) through 1 year post-transplant
Phase II - Percent of Patients With Treatment-related Deaths at 100 Days
Time frame: 100 days post transplant
Phase II - Percent of Patients With Treatment-related Deaths at 1 Year
Time frame: Transplant (Day 0) through 1 year post-transplant
Phase II - Time to Neutrophil Engraftment
Time frame: Transplant (Day 0) through 1 year post transplant
Phase II - Time to Platelet Engraftment
Time frame: Transplant (Day 0) through 1 year post-transplant

Results and safety

Results posted to the registry on 6 Dec 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Phase I Dose Finding	3	0
Phase II	11	1

Primary outcome: Phase I: Number of Participants With Dose Limiting Toxicity

Time frame: 28 days. Count of participants. Unit: Participants

Measure	Phase I Dose Finding n = 3
Value	0

Population analysed: All patients assigned to Phase I and received treatment medication.

Primary outcome: Phase II: Percent of Patients Alive and Free of Progression at 12 Months Following Transplant

Time frame: Transplant (Day 0) through 1 year post-transplant. Number (95% Confidence Interval). Unit: percentage of participants

Measure	Phase II n = 11
Value	18.2 (2.3 to 51.8)

Population analysed: All patients who received treatment and were followed after transplant.

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: up to 3 years. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Phase I Dose Finding	2 of 3 (66.7%)	3 of 3 (100%)	Not reported
Phase II	8 of 11 (72.7%)	11 of 11 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Multiple Myeloma

Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Active, not recruitingPhase 3
A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)
Multiple Myeloma
Active, not recruitingPhase 1/2
A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment
Multiple Myeloma
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Sherif Farag, MD, PhD principal investigator

IU Simon Cancer Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Sirolimus, Tacrolimus and Lenalidomide in people with Multiple Myeloma, run by Sherif S. Farag at 1 site in United States.

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

Who may be eligible to take part?

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 8 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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?

Yes. Results are posted in the registry (first posted 6 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Phase I: Number of Participants With Dose Limiting Toxicity (time frame: 28 days). 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 NCT01303965.

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 8 Jan 2019.