MyelomaPhase 1NCT01985477
Revlimid / All-Trans Retinoic Acid (ATRA) / Dexamethasone in Relapsed/Refractory Multiple Myeloma
A Phase 1 study testing Lenalidomide, Dexamethasone and All-Trans Retinoic Acid (ATRA) in people with Myeloma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of the Phase I portion of this clinical research study is to find the highest tolerated dose of the combination of lenalidomide, all-trans retinoic acid (ATRA), and dexamethasone that can be given to patients with relapsed or refractory multiple myeloma (MM). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myeloma
- What is being tested?
- Lenalidomide, Dexamethasone and All-Trans Retinoic Acid (ATRA)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2013to Sep 2015
- Phase
- Phase 1
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Understand and voluntarily sign an informed consent form
- Age >/= 18 years at the time of signing the informed consent form
- Serum creatinine </= 2.5 mg/dl OR Creatine clearance > 30 ml/min
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
- Females of childbearing potential (FCBP)* must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mlU/mL within 10-14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional affective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a female of childbearing potential even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
- Continuation from Inclusion #5: *A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
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- Able to take prophylactic antiplatelet/anticoagulation, warfarin or equivalent agent
- Patient is able to understand and comply with the terms and conditions of the Lenalidomide Counseling Program.
- Phase I Specific Inclusion Criteria: Multiple myeloma that has progressed on lenalidomide and dexamethasone combination therapy at a dose of 25 mg daily on lenalidomide and 40 mg weekly of dexamethasone with measurable levels of myeloma paraprotein in serum ( >/= 0.5 g/dl), urine ( >/= 0.2 g excreted in a 24-hour collection sample), or abnormal free light chain (FLC) ratio.
- Phase I Specific Inclusion Criteria: Laboratory test results within these ranges: Absolute neutrophil count > 1000 cells/mm^3; Platelet count > 100,000 cells/mm^3 for patients with < 50% of bone marrow plasma cells and platelet count > 50,000 cells/mm^3 for patients in whom > 50% of the bone marrow nucleated cells were plasma cells; Total bilirubin </= 2.0 mg/dL; AST (SGOT) and ALT (AGPT) < 3 x upper limits of normal (ULN)
- Phase II Specific Inclusion Criteria: Cohort A: Multiple myeloma that has progressed on lenalidomide and dexamethasone combination therapy with measurable levels of myeloma paraprotein in serum ( >/= 0.5 g/dl), urine ( >/= 0.2 g excreted in a 24-hour collection sample), or involved FLC level by more than 10 mg/dL and abnormal free light chain (FLC) ratio. Cohort B: Multiple myeloma that has progressed on single agent lenalidomide therapy with measurable disease defined as: doubling of the M-component in 2 consecutive measurements in less than or equal to 2 months OR increase in serum M-protein levels by >/= .5g or urine protein by 200mg/24 hours, or involved FLC level by more than 10 mg/dL (with an abnormal FLC ratio).
- Phase II Specific Inclusion Criteria: Laboratory test results within these ranges: Absolute neutrophil count > 1000 cells/mm^3; Platelet count > 75,000 cells/mm^3 for patients with < 50% of bone marrow plasma cells and platelet count > 50,000 cells/mm^3 for patients in whom > 50% of the bone marrow nucleated cells were plasma cells; Total bilirubin </= 2.0 mg/dL; AST (SGOT) and ALT (AGPT) < 3 x ULN
Who cannot join
- Any serious medical condition, or psychiatric illness that would prevent the subject from signing the informed consent form.
- Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
- Use of any cancer therapy within 14 days prior to beginning cycle 1 day 1 of therapy with the exception of lenalidomide and dexamethasone (radiation therapy allowed within 5 days of completion of radiation therapy)
- Known hypersensitivity to lenalidomide or ATRA.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Phase I/II Study of Lenalidomide (Revlimid), All-trans Retinoic Acid (ATRA) and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma
The goal of the Phase I portion of this clinical research study is to find the highest tolerated dose of the combination of lenalidomide, all-trans retinoic acid (ATRA), and dexamethasone that can be given to patients with relapsed or refractory multiple myeloma (MM).
The goal of the Phase II portion of this study is to learn if ATRA when given in combination with lenalidomide alone or with lenalidomide and dexamethasone can help to control multiple myeloma.
In September 2015, the study was terminated due to slow accrual while still a Phase I study, no additional registration or research performed under the Phase II portion of the study.
Read the detailed description
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you joined this study. Up to 2 groups of up to 3-6 patients participants will be enrolled in the Phase I portion of the study, and up to 58 participants will be enrolled in Phase II.
If you are enrolled in the Phase I portion, the dose of lenalidomide, dexamethasone, and ATRA you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of the combination. Each new group will receive a higher dose of the combination than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of the combination of lenalidomide and ATRA is found.
If you are enrolled in the Phase II portion, you will be assigned to 1 of 2 groups based on the therapy you were receiving before you began to take part in this study.
- If you were receiving lenalidomide alone, you will take lenalidomide and ATRA (Group A).
- If you were receiving lenalidomide and dexamethasone when you started this study, you will take lenalidomide, dexamethasone, and ATRA (Group B).
Study Drug Administration:
Each cycle is 28 days.
The first part of the study, called induction, will have 3 cycles. After that is the maintenance part of the study. You will be able to continue on maintenance for as long as the doctor thinks it is in your best interest.
Induction:
- On Day 1-21 of each cycle, you will take lenalidomide by mouth 1 time every day.
- On Days 1-21 of each cycle, you will take ATRA by mouth 2 times each day.
- On Days 1, 8, 15, and 22 of each cycle (+/- 3 days), you will take dexamethasone by mouth.
Maintenance:
- On Day 1-21 of each cycle, you will take lenalidomide by mouth 1 time every day.
- On Days 1-14 of each cycle, you will take ATRA by mouth 2 times each day.
- If you are in Group A, on Days 1, 8, 15, and 22 of each cycle (+/- 3 days), you will take dexamethasone by mouth.
If a dose of lenalidomide is missed or vomited, you should continue with the regular schedule of the drug at the next dose, and a missed dose should NOT be made up.
Lenalidomide capsules should be swallowed whole, and should not be broken, chewed or opened. If you take more than the prescribed dose of lenalidomide, you should seek emergency medical care if needed and contact study staff right away
Study Visits:
Induction Study Visits:
On Days 1, 8, and 15 of Cycle 1:
- You will have a physical exam.
- Blood (about 3 tablespoon) will be drawn for routine tests.
- Urine will be collected over 24 hours to check the status of the disease (Day 1 only).
Between Days 19 and 21 of Cycle 1, you will have a bone marrow aspiration and blood (about 1 teaspoon) will be drawn to measure the levels of certain proteins for research purposes.
On about Day 1 of Cycles 2-3:
- You will have a physical exam.
- Blood (about 3 tablespoons) will be drawn for routine tests
- Blood (about 1 teaspoon) will be drawn to measure proteins in your blood.
- Urine will be collected over 24 hours to check the status of the disease.
If your doctor thinks it is needed, the visits may take place more often. You may have extra visits at any time during the study if your doctor thinks it is needed for your care.
Maintenance Therapy Study Visits:
Once a month during Maintenance Therapy:
- You will have a physical exam.
- Blood (about 2 teaspoons) will be drawn for routine tests.
- Blood (about 1 teaspoon) will be drawn to measure proteins in your blood.
- Urine will be collected over 24 hours to check the status of the disease.
- If the doctor thinks it is needed, you will have a bone marrow biopsy to check the status of the disease.
Length of Study:
You will receive up to 3 cycles of the study drugs during induction. You may continue taking the study drugs during maintenance for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse if intolerable side effects occur, or you are unable to follow study directions.
Your participation on this study will be over after the end-of-study visit.
End-of-Study Visit:
If you go off study for any reason, you will have an end-of-study visit. This is usually done about 30 days after the last dose of the study drugs. At this visit, the following tests and procedures will be performed:
- You will have a physical exam.
- Blood (about 2-3 teaspoons) and urine (over 24 hours) will be collected to check the status of the disease.
- Blood (about 1 tablespoon) will be drawn for routine tests.
- If the doctor thinks it is needed, you will have a bone marrow biopsy to check the status of the disease.
This is an investigational study. ATRA is FDA approved and commercially available to treat acute promyelocytic leukemia.
Lenalidomide is FDA approved and commercially available to treat MM.
Dexamethasone is FDA approved and commercially available to treat inflammation and allergic conditions and to manage the symptoms of several types of leukemia and lymphoma.
The combination of ATRA, lenalidomide, and dexamethasone is investigational.
Up to 70 participants will be enrolled in this study. All will take part at MD Anderson.
- Conditions
- Myeloma
- Being tested
- Lenalidomide, Dexamethasone, All-Trans Retinoic Acid (ATRA)
- Keywords
- Myeloma, Multiple myeloma, MM, Relapsed/Refractory Multiple Myeloma, RR MM, Lenalidomide, CC-5013, Revlimid, Dexamethasone, Decadron, All-Trans Retinoic Acid, ATRA, Tretinoin (Oral), Vesanoid
- Medical subject headings
- Neoplasms, Plasma Cell, Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenalidomideDrug
Also called CC-5013, Revlimid
Phase I All Patients - Induction: Lenalidomide starting dose 25 mg by mouth 1 time every day on Day 1-21.
Phase II Group A: Lenalidomide starting dose: Dose tolerated prior to enrollment.
Maintenance Therapy: Phase I and Phase II Group A: Maintenance therapy lenalidomide at dose level tolerated at completion of cycle 3 for 21/28 days.
Phase II Group B: Lenalidomide will be given as a single oral dose at the level patient was on at the time of progression on single agent lenalidomide prior to study enrollment.
DexamethasoneDrug
Also called Decadron
Phase I All Patients - Induction: Dexamethasone starting dose 40 mg by mouth on Days 1,8,15,22.
Phase II Group A: Dexamethasone starting dose: Dose previously on when progressing prior to study entry.
Maintenance Therapy: Phase I and Phase II Group A: Dexamethasone at last tolerated dose on Days 1, 8, 15 and 22.
All-Trans Retinoic Acid (ATRA)Drug
Also called ATRA, Tretinoin (Oral), Vesanoid
Phase I All Patients - Induction: ATRA starting dose 25 mg/m2 by mouth 2 times each day on Days 1-21.
Phase II Group A: ATRA starting dose: MTD from Phase I.
Maintenance Therapy: Phase I and Phase II Group A: ATRA at dose determined in Phase I for 14/28 days.
Phase II Group B: All-Trans Retinoic Acid (ATRA) starting dose: MTD from Phase I.
Maintenance Therapy Group B: ATRA at the dose determined in the Phase I portion of the trial for 14/28 days.
| Study group | Role | What they receive |
|---|---|---|
| Lenalidomide + Dexamethasone + All-Trans Retinoic Acid (ATRA) | Experimental | Phase I All Patients - Induction: Lenalidomide starting dose 25 mg by mouth 1 time every day on Day 1-21. Dexamethasone starting dose 40 mg by mouth on Days 1,8,15,22. ATRA starting dose 25 mg/m2 by mouth 2 times each day on Days 1-21.
Phase II Group A: Lenalidomide starting dose: Dose tolerated prior to enrollment. Dexamethasone starting dose: Dose previously on when progressing prior to study entry. ATRA starting dose: MTD from Phase I.
Maintenance Therapy Group A: Lenalidomide at dose level tolerated at completion of cycle 3 for 21/28 days, with ATRA at dose determined in Phase I for 14/28 days, and Dexamethasone at last tolerated dose on Days 1, 8, 15 and 22. After 3 months on therapy at MTD in Phase I study, patients must be switched to this dose schedule. Patients unable to tolerate either Dexamethasone during maintenance phase may dose reduce Dexamethasone as needed. Receives: Drug: Lenalidomide; Drug: Dexamethasone; Drug: All-Trans Retinoic Acid (ATRA) |
| Lenalidomide + All-Trans Retinoic Acid (ATRA) | Experimental | Phase II Group B: Lenalidomide will be given as a single oral dose at the level patient was on at the time of progression on single agent Lenalidomide prior to study enrollment. All-Trans Retinoic Acid (ATRA) starting dose: MTD from Phase I.
Maintenance Therapy: Maintenance therapy consists of lenalidomide at the dose level tolerated at the completion of cycle 3 for 21/28 days, with ATRA at the dose determined in the phase I portion of the trial for 14/28 days. Dexamethasone will not be administered. After 3 months on therapy at the MTD in the phase 1 study, patients must be switched to this dose schedule. Receives: Drug: Lenalidomide; Drug: All-Trans Retinoic Acid (ATRA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of Lenalidomide/Dexamethasone and All-Trans Retinoic Acid (ATRA)
MTD defined as highest dose level in which 6 patients have been treated with less than 2 instances of dose limiting toxicity (DLT). Dose limiting toxicity refers to a medically significant event which meets one of the following:
Hematologic dose-limiting toxicity defined as either, Grade 4 neutropenia lasting for >/=14 days in duration ( growth factors permitted after DLT established), Grade 4 thrombocytopenia > 14 days despite platelet transfusions.
Non-hematologic DLT defined as any Grade 3, 4 or 5 non-hematologic toxicity, with the specific exception of, Isolated Grade 3 elevation of liver function tests (LFTs) without associated clinical symptoms, lasting for </=7 days in duration, Isolated Grade 3 elevation of amylase without associated clinical symptoms, Grade 3 hypocalcemia, hyperglycemia, hypokalemia, hypomagnesemia, hyponatremia, or hypophosphatemia which responds to medical intervention.
Measured: 28 days
Secondary outcomes (1)
Objective Response
The objective response (complete response + partial response) at 4 cycles is the primary endpoint. Patients assessed for response each cycle of therapy according to International Myeloma Working Group Criteria.
Measured: After 4, 28 day cycles
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2013 (estimated)
- Study startDec 2013
- Primary completionSep 2015
- Study completionSep 2015
Why it stopped: Terminated Phase I due to slow accrual without progression to Phase II.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MyelomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene Corporation
- Responsible party
- Sponsor
- Investigators
- Jatin J. Shah, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01985477
- Sponsor's protocol ID
- 2013-0624
- Other IDs
- NCI-2014-01098
- Status last verified
- Sep 2016
- First submitted
- 8 Nov 2013
- Last updated
- 14 Sep 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Lenalidomide (Revlimid), All-trans Retinoic Acid (ATRA) and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT01985477
- Acronym / sponsor ID
- 2013-0624
- Conditions
- Myeloma
- Keywords
- Myeloma, Multiple myeloma, MM, Relapsed/Refractory Multiple Myeloma, RR MM, Lenalidomide, CC-5013, Revlimid
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated Phase I due to slow accrual without progression to Phase II.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Celgene Corporation
- Study start
- Dec 2013
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 15 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of the Phase I portion of this clinical research study is to find the highest tolerated dose of the combination of lenalidomide, all-trans retinoic acid (ATRA), and dexamethasone that can be given to patients with relapsed or refractory multiple myeloma (MM).
The goal of the Phase II portion of this study is to learn if ATRA when given in combination with lenalidomide alone or with lenalidomide and dexamethasone can help to control multiple myeloma.
In September 2015, the study was terminated due to slow accrual while still a Phase I study, no additional registration or research performed under the Phase II portion of the study.
Detailed description
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you joined this study. Up to 2 groups of up to 3-6 patients participants will be enrolled in the Phase I portion of the study, and up to 58 participants will be enrolled in Phase II.
If you are enrolled in the Phase I portion, the dose of lenalidomide, dexamethasone, and ATRA you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of the combination. Each new group will receive a higher dose of the combination than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of the combination of lenalidomide and ATRA is found.
If you are enrolled in the Phase II portion, you will be assigned to 1 of 2 groups based on the therapy you were receiving before you began to take part in this study.
- If you were receiving lenalidomide alone, you will take lenalidomide and ATRA (Group A).
- If you were receiving lenalidomide and dexamethasone when you started this study, you will take lenalidomide, dexamethasone, and ATRA (Group B).
Study Drug Administration:
Each cycle is 28 days.
The first part of the study, called induction, will have 3 cycles. After that is the maintenance part of the study. You will be able to continue on maintenance for as long as the doctor thinks it is in your best interest.
Induction:
- On Day 1-21 of each cycle, you will take lenalidomide by mouth 1 time every day.
- On Days 1-21 of each cycle, you will take ATRA by mouth 2 times each day.
- On Days 1, 8, 15, and 22 of each cycle (+/- 3 days), you will take dexamethasone by mouth.
Maintenance:
- On Day 1-21 of each cycle, you will take lenalidomide by mouth 1 time every day.
- On Days 1-14 of each cycle, you will take ATRA by mouth 2 times each day.
- If you are in Group A, on Days 1, 8, 15, and 22 of each cycle (+/- 3 days), you will take dexamethasone by mouth.
If a dose of lenalidomide is missed or vomited, you should continue with the regular schedule of the drug at the next dose, and a missed dose should NOT be made up.
Lenalidomide capsules should be swallowed whole, and should not be broken, chewed or opened. If you take more than the prescribed dose of lenalidomide, you should seek emergency medical care if needed and contact study staff right away
Study Visits:
Induction Study Visits:
On Days 1, 8, and 15 of Cycle 1:
- You will have a physical exam.
- Blood (about 3 tablespoon) will be drawn for routine tests.
- Urine will be collected over 24 hours to check the status of the disease (Day 1 only).
Between Days 19 and 21 of Cycle 1, you will have a bone marrow aspiration and blood (about 1 teaspoon) will be drawn to measure the levels of certain proteins for research purposes.
On about Day 1 of Cycles 2-3:
- You will have a physical exam.
- Blood (about 3 tablespoons) will be drawn for routine tests
- Blood (about 1 teaspoon) will be drawn to measure proteins in your blood.
- Urine will be collected over 24 hours to check the status of the disease.
If your doctor thinks it is needed, the visits may take place more often. You may have extra visits at any time during the study if your doctor thinks it is needed for your care.
Maintenance Therapy Study Visits:
Once a month during Maintenance Therapy:
- You will have a physical exam.
- Blood (about 2 teaspoons) will be drawn for routine tests.
- Blood (about 1 teaspoon) will be drawn to measure proteins in your blood.
- Urine will be collected over 24 hours to check the status of the disease.
- If the doctor thinks it is needed, you will have a bone marrow biopsy to check the status of the disease.
Length of Study:
You will receive up to 3 cycles of the study drugs during induction. You may continue taking the study drugs during maintenance for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse if intolerable side effects occur, or you are unable to follow study directions.
Your participation on this study will be over after the end-of-study visit.
End-of-Study Visit:
If you go off study for any reason, you will have an end-of-study visit. This is usually done about 30 days after the last dose of the study drugs. At this visit, the following tests and procedures will be performed:
- You will have a physical exam.
- Blood (about 2-3 teaspoons) and urine (over 24 hours) will be collected to check the status of the disease.
- Blood (about 1 tablespoon) will be drawn for routine tests.
- If the doctor thinks it is needed, you will have a bone marrow biopsy to check the status of the disease.
This is an investigational study. ATRA is FDA approved and commercially available to treat acute promyelocytic leukemia.
Lenalidomide is FDA approved and commercially available to treat MM.
Dexamethasone is FDA approved and commercially available to treat inflammation and allergic conditions and to manage the symptoms of several types of leukemia and lymphoma.
The combination of ATRA, lenalidomide, and dexamethasone is investigational.
Up to 70 participants will be enrolled in this study. All will take part at MD Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lenalidomide + Dexamethasone + All-Trans Retinoic Acid (ATRA) | Experimental | Drug: Lenalidomide, Drug: Dexamethasone, Drug: All-Trans Retinoic Acid (ATRA)Phase I All Patients - Induction: Lenalidomide starting dose 25 mg by mouth 1 time every day on Day 1-21. Dexamethasone starting dose 40 mg by mouth on Days 1,8,15,22. ATRA starting dose 25 mg/m2 by mouth 2 times each day on Days 1-21. Phase II Group A: Lenalidomide starting dose: Dose tolerated prior to enrollment. Dexamethasone starting dose: Dose previously on when progressing prior to study entry. ATRA starting dose: MTD from Phase I. Maintenance Therapy Group A: Lenalidomide at dose level tolerated at completion of cycle 3 for 21/28 days, with ATRA at dose determined in Phase I for 14/28 days, and Dexamethasone at last tolerated dose on Days 1, 8, 15 and 22. After 3 months on therapy at MTD in Phase I study, patients must be switched to this dose schedule. Patients unable to tolerate either Dexamethasone during maintenance phase may dose reduce Dexamethasone as needed. |
| Lenalidomide + All-Trans Retinoic Acid (ATRA) | Experimental | Drug: Lenalidomide, Drug: All-Trans Retinoic Acid (ATRA)Phase II Group B: Lenalidomide will be given as a single oral dose at the level patient was on at the time of progression on single agent Lenalidomide prior to study enrollment. All-Trans Retinoic Acid (ATRA) starting dose: MTD from Phase I. Maintenance Therapy: Maintenance therapy consists of lenalidomide at the dose level tolerated at the completion of cycle 3 for 21/28 days, with ATRA at the dose determined in the phase I portion of the trial for 14/28 days. Dexamethasone will not be administered. After 3 months on therapy at the MTD in the phase 1 study, patients must be switched to this dose schedule. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Understand and voluntarily sign an informed consent form
- Age >/= 18 years at the time of signing the informed consent form
- Serum creatinine </= 2.5 mg/dl OR Creatine clearance > 30 ml/min
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
- Females of childbearing potential (FCBP)* must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mlU/mL within 10-14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional affective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a female of childbearing potential even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
Key exclusion criteria (4 listed)
- Any serious medical condition, or psychiatric illness that would prevent the subject from signing the informed consent form.
- Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
- Use of any cancer therapy within 14 days prior to beginning cycle 1 day 1 of therapy with the exception of lenalidomide and dexamethasone (radiation therapy allowed within 5 days of completion of radiation therapy)
- Known hypersensitivity to lenalidomide or ATRA.
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 |
|---|---|---|
| LenalidomideAlso: CC-5013, RevlimidPhase I All Patients - Induction: Lenalidomide starting dose 25 mg by mouth 1 time every day on Day 1-21. Phase II Group A: Lenalidomide starting dose: Dose tolerated prior to enrollment. Maintenance Therapy: Phase I and Phase II Group A: Maintenance therapy lenalidomide at dose level tolerated at completion of cycle 3 for 21/28 days. Phase II Group B: Lenalidomide will be given as a single oral dose at the level patient was on at the time of progression on single agent lenalidomide prior to study enrollment. | Drug | Lenalidomide + All-Trans Retinoic Acid (ATRA), Lenalidomide + Dexamethasone + All-Trans Retinoic Acid (ATRA) |
| DexamethasoneAlso: DecadronPhase I All Patients - Induction: Dexamethasone starting dose 40 mg by mouth on Days 1,8,15,22. Phase II Group A: Dexamethasone starting dose: Dose previously on when progressing prior to study entry. Maintenance Therapy: Phase I and Phase II Group A: Dexamethasone at last tolerated dose on Days 1, 8, 15 and 22. | Drug | Lenalidomide + Dexamethasone + All-Trans Retinoic Acid (ATRA) |
| All-Trans Retinoic Acid (ATRA)Also: ATRA, Tretinoin (Oral), VesanoidPhase I All Patients - Induction: ATRA starting dose 25 mg/m2 by mouth 2 times each day on Days 1-21. Phase II Group A: ATRA starting dose: MTD from Phase I. Maintenance Therapy: Phase I and Phase II Group A: ATRA at dose determined in Phase I for 14/28 days. Phase II Group B: All-Trans Retinoic Acid (ATRA) starting dose: MTD from Phase I. Maintenance Therapy Group B: ATRA at the dose determined in the Phase I portion of the trial for 14/28 days. | Drug | Lenalidomide + All-Trans Retinoic Acid (ATRA), Lenalidomide + Dexamethasone + All-Trans Retinoic Acid (ATRA) |
Primary outcome
Maximum Tolerated Dose (MTD) of Lenalidomide/Dexamethasone and All-Trans Retinoic Acid (ATRA)
Time frame: 28 days
MTD defined as highest dose level in which 6 patients have been treated with less than 2 instances of dose limiting toxicity (DLT). Dose limiting toxicity refers to a medically significant event which meets one of the following: Hematologic dose-limiting toxicity defined as either, Grade 4 neutropenia lasting for >/=14 days in duration ( growth factors permitted after DLT established), Grade 4 thrombocytopenia > 14 days despite platelet transfusions. Non-hematologic DLT defined as any Grade 3, 4 or 5 non-hematologic toxicity, with the specific exception of, Isolated Grade 3 elevation of liver function tests (LFTs) without associated clinical symptoms, lasting for </=7 days in duration, Isolated Grade 3 elevation of amylase without associated clinical symptoms, Grade 3 hypocalcemia, hyperglycemia, hypokalemia, hypomagnesemia, hyponatremia, or hypophosphatemia which responds to medical intervention.
1 secondary outcome
Objective Response
Time frame: After 4, 28 day cycles
Results and safety
The study was stopped early (reason given: Terminated Phase I due to slow accrual without progression to Phase II.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2016.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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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.
Jatin J. Shah, MD principal investigator
M.D. Anderson 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 study testing Lenalidomide, Dexamethasone and All-Trans Retinoic Acid (ATRA) in people with Myeloma, run by M.D. Anderson Cancer Center 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?
The sponsor lists 12 inclusion and 4 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 14 Sep 2016. 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 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.
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: Terminated Phase I due to slow accrual without progression to Phase II.). 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?
Maximum Tolerated Dose (MTD) of Lenalidomide/Dexamethasone and All-Trans Retinoic Acid (ATRA) (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Sep 2016.